Hippocampal neuro-networks and dendritic spine perturbations in epileptogenesis are attenuated by neuroprotectin D1
Open accessAbstract
PURPOSE: Limbic epileptogenesis triggers molecular and cellular events that foster the establishment of aberrant neuronal networks that, in turn, contribute to temporal lobe epilepsy (TLE). Here we have examined hippocampal neuronal network activities in the pilocarpine post-status epilepticus model of limbic epileptogenesis and asked whether or not the docosahexaenoic acid (DHA)-derived lipid mediator, neuroprotectin D1 (NPD1), modulates epileptogenesis. METHODS: Status epilepticus (SE) was induced by intraperitoneal administration of pilocarpine in adult male C57BL/6 mice. To evaluate simultaneous hippocampal neuronal networks, local field potentials were recorded from multi-microelectrode arrays (silicon probe) chronically implanted in the dorsal hippocampus. NPD1 (570 μg/kg) or vehicle was administered intraperitoneally daily for five consecutive days 24 hours after termination of SE. Seizures and epileptiform activity were analyzed in freely-moving control and treated mice during epileptogenesis and epileptic periods. Then hippocampal dendritic spines were evaluated using Golgi-staining. RESULTS: We found brief spontaneous microepileptiform activity with high amplitudes in the CA1 pyramidal and stratum radiatum in epileptogenesis. These aberrant activities were attenuated following systemic NPD1 administration, with concomitant hippocampal dendritic spine protection. Moreover, NPD1 treatment led to a reduction in spontaneous recurrent seizures. CONCLUSIONS: Our results indicate that NPD1 displays neuroprotective bioactivity on the hippocampal neuronal network ensemble that mediates aberrant circuit activity during epileptogenesis. Insight into the molecular signaling mediated by neuroprotective bioactivity of NPD1 on neuronal network dysfunction may contribute to the development of anti-epileptogenic therapeutic strategies.
AI snapshot
Written from the paper’s full text.
TL;DR
In a pilocarpine post-status epilepticus mouse model, hippocampal epileptogenesis was accompanied by brief high-amplitude microepileptiform activity (MEA), low-voltage activity, and dendritic spine loss. Systemic neuroprotectin D1 (NPD1) given for five days after status epilepticus attenuated MEA, reduced spontaneous recurrent seizures, and protected hippocampal dendritic spines.
Key findings
- During epileptogenesis at 7 days post-SE, mice showed brief spontaneous MEA not seen in controls: 4.6 ± 1.06 events per delta epoch, duration 0.8 ± 0.14 sec, with high amplitude mainly in CA1 pyramidal and stratum radiatum layers.
- NPD1 reduced MEA number (NPD1 0.8 ± 0.28 vs vehicle 2.09 ± 0.15, P = 0.007) and duration (NPD1 0.7 ± 0.07 vs vehicle 1.72 ± 0.2, P = 0.013), and reduced high-frequency activity above 200 Hz in the dentate gyrus.
- At three weeks after SE, NPD1-treated mice had reduced spontaneous recurrent seizure severity (Racine score 1.2 ± 0.2 vs vehicle 3.16 ± 0.6, P = 0.0019), duration (2.74 ± 0.72 vs 7.23 ± 0.6, P = 0.014), and spike number (1.5 ± 0.86 vs 21.93 ± 3.23, P = 0.009).
- SE reduced dendritic spine density in CA1 stratum radiatum (control 0.78 ± 0.06 vs epileptogenesis 0.62 ± 0.03, p = 0.03) and dentate gyrus (control 0.82 ± 0.054 vs epileptogenesis 0.67 ± 0.03, p = 0.02); NPD1-treated mice showed higher spine density than vehicle-treated mice across hippocampal layers and fewer beading-like profiles.
Methods
- Status epilepticus was induced with pilocarpine hydrochloride (250 mg/kg i.p.) after methyl scopolamine nitrate (1 mg/kg i.p.) in 52 adult male C57BL/6 mice; 45 survived (60%), and controls (n = 10) received methyl scopolamine.
- A 16-electrode silicon probe was implanted in the dorsal hippocampus; local field potentials were recorded in freely-moving mice on day 7 and days 21–28 after SE, with seizures scored by Racine scale and dendritic spines assessed by Golgi staining at 7 days post-SE.
- NPD1 (570 μg/kg) or vehicle was administered i.p. daily for five consecutive days starting 24 hours after SE termination; data were analyzed with means ± S.E.M., t-tests, ANOVA with post-hoc tests, and cumulative probability/log-rank tests.
Limitations
- The paper does not include a dedicated limitations section. It states that the precise neurotransmission mechanism mediated by NPD1 in epileptogenesis remains to be further defined and that further studies are needed.
- Evident from the text: small group sizes (e.g., LFP n = 7 per group; seizure analysis n = 5 NPD1 vs n = 6 vehicle; spine analysis n = 4 per group; PSE vs control n = 3), use of only adult male C57BL/6 mice, a single pilocarpine model, and no dose-response or long-term follow-up beyond approximately three weeks after SE.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 55 cited sources checked · 0 supported · 0 flagged
- Findingown data
NPD1 administration protects hippocampal dendritic spines in epileptogenesis.
“These aberrant activities were attenuated following systemic NPD1 administration, with concomitant hippocampal dendritic spine protection.”
- Also stated in: § Introduction · plain
“We observed that NPD1 reduces brief spontaneous epileptiform field potentials and dendritic spine loss in the dorsal hippocampus, with resultant limited hippocampal epileptic activity.”
Quote in the paperSubstantial claim- Rests on an assumption: NPD1 administered intraperitoneally at 570 μg/kg for five consecutive days reaches the hippocampus and engages neuroprotective signaling.
- Rests on an assumption: Dendritic spine number measured by Golgi staining is a valid proxy for synaptic integrity and network function.
- Also stated in: § Introduction · plain
- Findingown data
Attenuation of low frequency bands (delta, theta, beta, gamma) is present in all hippocampal layers except theta in SO and PYR during epileptogenesis.
“In addition, attenuation of low frequency bands (i.e., delta, theta, beta and gamma) were present in all hippocampal layers except theta, in the SO and PYR (Fig. 3).”
Quote in the paperNot a substantial claim - Findingown data
Brief spontaneous microepileptiform activity with high amplitudes occurs in the CA1 pyramidal and stratum radiatum during epileptogenesis.
“We found brief spontaneous microepileptiform activity with high amplitudes in the CA1 pyramidal and stratum radiatum in epileptogenesis.”
- Also stated in: § Results · plain
“LVA was interrupted by an unexpected brief spontaneous micro-epileptiform activity (MEA) (Fig. 2B).”
- Also stated in: § Results · plain
“MEA was characterized by successive bursts of spikes with high amplitudes (Fig. 2B), mainly in the PYR and RAD (P = 0.007 vs. LVA) (Fig. 2E) simultaneously in all hippocampal layers (4.6 ± 1.06 events/per delta epoch; with duration of 0.8 sec ± 0.14 sec) (Fig. 2 B–D).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
At seven days after SE, the dorsal hippocampus displays disruptions in electrical patterns in all hippocampal layers.
“At seven days after SE and during periods of immobility in freely-moving mice, although convulsive seizures were not observed (Racine’s score > 3), consistent with previous observations [34, 35] the dorsal hippocampus displayed disruptions in electrical patterns, mainly in all hippocampal layers (Fig. 2A).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [34] J Seo, 2012, Early deficits in social behavior and cortical rhythms in pilocarpine-induced mouse model of temporal lobe epilepsy, Exp Neurol S0014–4886
Not checked in the free run.
- cites [35] H Shibley, 2002, Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice, Epilepsy Res source
Not checked in the free run.
- Findingown data
NPD1 administration attenuates aberrant microepileptiform activities in epileptogenesis.
“These aberrant activities were attenuated following systemic NPD1 administration, with concomitant hippocampal dendritic spine protection.”
- Also stated in: § Introduction · plain
“We observed that NPD1 reduces brief spontaneous epileptiform field potentials and dendritic spine loss in the dorsal hippocampus, with resultant limited hippocampal epileptic activity.”
Quote in the paperSubstantial claim- Rests on an assumption: NPD1 administered intraperitoneally at 570 μg/kg for five consecutive days reaches the hippocampus and engages neuroprotective signaling.
- Also stated in: § Introduction · plain
- Findingown data
Ripples are associated with a marked reduction of amplitude in the hippocampal CA1 RAD in epileptogenesis.
“The ripples were associated with a marked reduction of amplitude in the hippocampal CA1 RAD (p = 0.002 vs. control mice), which attenuates sharp wave profiles (Fig. 2A).”
Quote in the paperSubstantial claim - Findingown data
NPD1 treatment reduces spontaneous recurrent seizures.
“Moreover, NPD1 treatment led to a reduction in spontaneous recurrent seizures.”
Quote in the paperSubstantial claim- Rests on an assumption: NPD1 administered intraperitoneally at 570 μg/kg for five consecutive days reaches the hippocampus and engages neuroprotective signaling.
- Findingown data
The DG field potential shows a lack of dentate spikes associated with an increase in signal power at frequencies above 150 Hz in epileptogenesis, persisting three weeks after SE.
“Also, the DG field potential showed a lack of dentate spikes associated with an increase in signal power at frequencies above 150 Hz (p<0.05 vs. control mice) (Fig. 2A) that persisted three weeks after SE.”
Quote in the paperSubstantial claim - Findingown data
MEA is not observed in control animals.
“Although fluctuations in amplitude were present in neuronal circuitry, these type of discharges were not observed in control animals (Fig. 2C and D).”
Quote in the paperNot a substantial claim - Findingown data
NPD1 limited the severity of the epileptic discharge from the pyramidal layer by attenuating the number of spikes compared with vehicle-treated mice.
“Also, NPD1 limited the severity of the epileptic discharge from pyramidal layer by attenuating the number of spikes compared with vehicle-treated mice (Fig. 6F).”
Quote in the paperSubstantial claim - Findingown data
Pathological high-frequency oscillations precede microepileptiform discharges.
“We observed that pHFOs precede microepileptiform discharges (Fig. 2A and B)”
Quote in the paperSubstantial claim - Findingown data
NPD1 administration during epileptogenesis reduced the severity (Racine's score) of severe spontaneous seizures compared with vehicle-treated mice.
“Racine’s score: NPD1: 1.2 ± 0.2 S.E.M. vs. Vehicle: 3.16 ± 0.6 S.E.M., P = 0.0019”
Quote in the paperSubstantial claim - Findingown data
Brief hippocampal spontaneous epileptiform activity, denoted MEA, was observed when animals were quiet or still 7 days after status epilepticus.
“We observed brief hippocampal spontaneous epileptiform activity, which we denoted as MEA, when animals were quiet or still 7 days after SE.”
Quote in the paperNot a substantial claim - Findingown data
Dendritic swelling and beading were present as a consequence of status epilepticus.
“Also, dendritic swelling and beading, both of which are hallmarks of dendritic injury [38], were present as a consequence of SE.”
Quote in the paperSubstantial claim - Findingown data
After 7 days of status epilepticus, the number of dendritic spines per dendrite segment was reduced in the dentate gyrus compared with control.
“DG: Control: 0.82 ± 0.054 S.E.M. vs. Epileptogenesis: 0.67 ± 0.03 S.E.M., p = 0.02) after 7 days of SE.”
Quote in the paperSubstantial claim - Findingown data
NPD1 reduced signal power at frequencies above 200 Hz in the dentate gyrus.
“Also, NPD1 reduced signal power at frequencies above 200 Hz in the DG (Fig. 5E and F).”
Quote in the paperNot a substantial claim - Findingown data
Isolated pathological high-frequency oscillations in the dentate gyrus occur as a consequence of status epilepticus.
“Also, isolated pHFOs in the DG, as a consequence of SE (Fig. 2 A, B)”
Quote in the paperNot a substantial claim - Findingown data
Systemic NPD1 administration during five consecutive days after SE attenuated the number of MEA compared with vehicle.
“the present study discloses that systemic administration of this lipid mediator, during five consecutive days after SE (see Methods), remarkably attenuated the amplitude and number of MEA (NPD1: 0.8 ± 0.28 SEM vs. Vehicle: 2.09 ± 0.15 S.E.M.; P = 0.007)”
Quote in the paperSubstantial claim - Findingown data
Systemic NPD1 administration during five consecutive days after SE attenuated the amplitude of micro-epileptiform activity (MEA) compared with vehicle.
“the present study discloses that systemic administration of this lipid mediator, during five consecutive days after SE (see Methods), remarkably attenuated the amplitude and number of MEA (NPD1: 0.8 ± 0.28 SEM vs. Vehicle: 2.09 ± 0.15 S.E.M.; P = 0.007)”
Quote in the paperSubstantial claim - Findingown data
After 7 days of status epilepticus, the number of dendritic spines per dendrite segment was reduced in CA1 (stratum radiatum) compared with control.
“we observed a reduction of the number of dendritic spines per dendrite segment in CA1 and dentate gyrus regions (Fig. 7A, B, RAD: Control: 0.78 ± 0.06 S.E.M. vs. Epileptogenesis: 0.62 ± 0.03 S.E.M., p = 0.03”
Quote in the paperSubstantial claim - Findingown data
Systemic NPD1 administration during five consecutive days after SE reduced the duration of MEA compared with vehicle.
“as well as their duration (NPD1: 0.7 ± 0.07 S.E.M. vs. Vehicle: 1.72 ± 0.2 S.E.M.; P = 0.013) (Fig. 5D).”
Quote in the paperSubstantial claim - Findingown data
Convulsive seizures were not observed at seven days after SE.
“At seven days after SE and during periods of immobility in freely-moving mice, although convulsive seizures were not observed (Racine’s score > 3), consistent with previous observations [34, 35] the dorsal hippocampus displayed disruptions in electrical patterns, mainly in all hippocampal layers (Fig. 2A).”
Quote in the paperNot a substantial claim - Findingown data
The amplitude of MEA was higher in the pyramidal layer and stratum radiatum.
“Since their amplitude was higher in the PYR and RAD”
Quote in the paperNot a substantial claim - Findingcitation
Physiological patterns in hippocampal layers (deep-voltage profiles, ripple sharp wave complex, DG spikes) were observed in control animals, allowing recognition of neuronal network assemblies.
“We observed, in agreement with Buzsáki and colleagues [21], physiological patterns in hippocampal layers that included deep-voltage profiles, the ripple sharp wave complex, and DG spikes in control animals, allowing for recognition of neuronal network assemblies (Fig. 1C–E, Fig. 2A) relevant to hippocampal function [21] and inter-ictal or seizure state.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] G Buzsáki, 2003, Hippocampal network patterns of activity in the mouse, Neuroscience source
Not checked in the free run.
- Findingown data
At seven days after status epilepticus, NPD1 administration resulted in higher density of spines from the dendrites of both CA1 pyramidal and dentate gyrus granular cells compared to vehicle-treated mice.
“NPD1 administration showed higher density of spines from the dendrites of both CA1 PYR and DG-granular cells compared to vehicle-treated mice”
Quote in the paperSubstantial claim - Findingown data
NPD1 administration induced less beading-like profiles in CA1 and dentate gyrus compared to vehicle-treated mice.
“and induced less beading-like profiles (CA1: NPD1: 0.65 ± 0.16 S.E.M vs. Vehicle: 3.44 ± 0.41 S.E.M.; DG: NPD1 0.65 ± 0016 S.E.M. vs. Vehicle: 3.44± 0.39 S.E.M., p;<0.0001; Fig. 7 E).”
Quote in the paperSubstantial claim - Findingown data
NPD1 administration during epileptogenesis reduced the duration of severe spontaneous seizures compared with vehicle-treated mice.
“Duration: NPD1: 2.74 ± 0.72 S.E.M. vs. Vehicle: 7.23 ± 0.6 S.E.M., P = 0.014”
Quote in the paperSubstantial claim - Findingown data
NPD1 administration during epileptogenesis reduced the number of spikes compared with vehicle-treated mice.
“spikes: NPD1: 1.5 ± 0.86 S.E.M. vs. Vehicle: 21.93 ± 3.23 S.E.M. P = 0.009”
Quote in the paperSubstantial claim - Premisecitation
Hippocampal NPD1 pool size increases after seizures.
“Hippocampal NPD1 pool size increases after seizures [15].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] AE Musto, 2011, The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis, Epilepsia source
Not checked in the free run.
- Interpretationreasoning
NPD1-molecular signaling could modulate neuronal circuitry-modified mechanisms in epileptogenesis.
“Therefore, NPD1-molecular signaling could modulate neuronal circuitry-modified mechanisms in epileptogenesis.”
Quote in the paperSubstantial claim - Interpretationown data
The low voltage activity (LVA) pattern reflects a global neuronal network disruption within the hippocampus.
“Since voltage reduction was predominant during this post-status epileptic period, we denoted this electrical pattern as low voltage activity (LVA), reflecting a global neuronal network disruption within the hippocampus (Fig. 2A, Fig. 3).”
Quote in the paperNot a substantial claim - Interpretationown data
NPD1 displays neuroprotective bioactivity on the hippocampal neuronal network ensemble that mediates aberrant circuit activity during epileptogenesis.
“Our results indicate that NPD1 displays neuroprotective bioactivity on the hippocampal neuronal network ensemble that mediates aberrant circuit activity during epileptogenesis.”
Quote in the paperSubstantial claim- Rests on an assumption: NPD1 administered intraperitoneally at 570 μg/kg for five consecutive days reaches the hippocampus and engages neuroprotective signaling.
- Rests on an assumption: Dendritic spine number measured by Golgi staining is a valid proxy for synaptic integrity and network function.
- Premisecitation
Limbic epileptogenesis involves a partially-understood molecular cascade that results in aberrant neuronal connectivity and chronic recurrent spontaneous seizures.
“Development of TLE or limbic epileptogenesis [4, 5] involves a partially-understood molecular cascade [6] that results in aberrant neuronal connectivity [7, 8] from a multi-architecture neuronal network of the limbic system connected to hippocampal formation [9] that contributes to a systemic process in the brain that leads to chronic recurrent spontaneous seizures [10].”
Quote in the paperSubstantial claim0 of 5 sources checked- cites [4] FE Dudek, 2011, Seizure probability in animal models of acquired epilepsy: a perspective on the concept of the preictal state, Epilepsy Res source
Not checked in the free run.
- cites [5] J Helgager, 2013, The cellular and synaptic location of activated TrkB in mouse hippocampus during limbic epileptogenesis, J Comp Neurol source
Not checked in the free run.
- cites [6] A Pitkänen, 2011, Molecular biomarkers of epileptogenesis, Biomark Med source
Not checked in the free run.
- cites [7] JJ McAuliffe, 2011, Altered patterning of dentate granule cell mossy fiber inputs onto CA3 pyramidal cells in limbic epilepsy, Hippocampus source
Not checked in the free run.
- cites [8] EH Bertram, 2013, Neuronal circuits in epilepsy: do they matter?, Exp Neurol source
Not checked in the free run.
- Premisecitation
Intra-cerebral NPD1 administration reduces seizure susceptibility in a kindling mouse model.
“Intra-cerebral NPD1 administration reduces seizure susceptibility in a kindling mouse model [15]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] AE Musto, 2011, The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis, Epilepsia source
Not checked in the free run.
- Premisecitation
Dendritic spines are a key target for neuronal network assemblies damaged during epilepsy.
“a key target for neuronal network assemblies damaged during epilepsy [37]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] JE Kurz, 2008, A cellular mechanism for dendritic spine loss in the pilocarpine model of status epilepticus, Epilepsia source
Not checked in the free run.
- Interpretationcitation
The aberrant neuronal network activity observed from LFP recordings may reflect linearly-summed postsynaptic potentials from small populations of principal cells that take place in dendritic spines that survive after status epilepticus.
“The aberrant neuronal network activity observed here from LFP recordings may reflect the linearly-summed postsynaptic potentials from small populations of principal cells [21, 53] that takes place in dendritic spines [34, 54] that survive after SE.”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [21] G Buzsáki, 2003, Hippocampal network patterns of activity in the mouse, Neuroscience source
Not checked in the free run.
- cites [53] R Galvez, 2006, Vibrissa-signaled eyeblink conditioning induces somatosensory cortical plasticity, J Neurosci source
Not checked in the free run.
- cites [34] J Seo, 2012, Early deficits in social behavior and cortical rhythms in pilocarpine-induced mouse model of temporal lobe epilepsy, Exp Neurol S0014–4886
Not checked in the free run.
- cites [54] N Takahashi, 2012, Locally synchronized synaptic inputs, Science source
Not checked in the free run.
- Interpretationreasoning
NPD1 modulates the neuronal network in the CA1 during ictogenesis.
“suggesting that NPD1 modulates the neuronal network in the CA1 during ictogenesis, which is critical in kindling epileptogenesis [15] and in human and experimental TLE [48].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [15] AE Musto, 2011, The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis, Epilepsia source
Not checked in the free run.
- cites [48] C Dinocourt, 2003, Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures, J Comp Neurol source
Not checked in the free run.
- Premisecitation
Dendritic spine reorganization in the dentate gyrus occurs during seizure susceptibility, development and spontaneous recurrent seizures.
“Dendritic spine reorganization in the DG occurs during seizure susceptibility, development and spontaneous recurrent seizures [44].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [44] E Danzer, 2010, The relationship of seizure activity and chronic epilepsy in early infancy and short-term neurodevelopmental outcome following fetal myelomeningocele closure, Neuropediatrics source
Not checked in the free run.
- Interpretationreasoning
NPD1 could prevent aberrant connectivity in the hippocampus.
“and thus could prevent aberrant connectivity in the hippocampus.”
Quote in the paperSubstantial claim - Premisecitation
Previously, hippocampal hyperexcitability followed by electrical stimulation in the CA1 region was observed to be attenuated by NPD1.
“Previously, we observed that hippocampal hyperexcitability, followed by electrical stimulation in the CA1 region, is attenuated by NPD1 [15].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] AE Musto, 2011, The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis, Epilepsia source
Not checked in the free run.
- Premisecitation
Chronic recurrent seizures are a consequence of pilocarpine-induced status epilepticus in all adult mice.
“Since chronic recurrent seizures are a consequence of pilocarpine-induced SE in all adult mice [27, 34, 35]”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [27] J Csicsvari, 1998, Reliability and state dependence of pyramidal cell-interneuron synapses in the hippocampus: an ensemble approach in the behaving rat, Neuron source
Not checked in the free run.
- cites [34] J Seo, 2012, Early deficits in social behavior and cortical rhythms in pilocarpine-induced mouse model of temporal lobe epilepsy, Exp Neurol S0014–4886
Not checked in the free run.
- cites [35] H Shibley, 2002, Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice, Epilepsy Res source
Not checked in the free run.
- May combine two claims. 19
- Classified as probably not a substantial claim. 18
May combine two claims.
Findingown dataNPD1 provides protection for dendrites and dendritic spines during epileptogenesis, reaching a similar number of dendrites as control animals.
“we showed that NPD1 could provide protection for dendrites and dendritic spines during epileptogenesis, which reached up to a similar number of dendrites for animals from the control group (S2 Fig.: CA1 L-M: NPD1 1 ± 0.08 S.E.M. vs. Control: 0.82 ± 0.16 S.E.M., p: 0.2; DG: NPD1: 1.18 ± 0.10 S.E.M. vs. Control: 1.14 ± 0.11 S.E.M., p: 0.7)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataMEA is characterized by successive bursts of spikes with high amplitudes, mainly in PYR and RAD, simultaneously in all hippocampal layers, with 4.6 ± 1.06 events per delta epoch and duration 0.8 ± 0.14 sec.
“MEA was characterized by successive bursts of spikes with high amplitudes (Fig. 2B), mainly in the PYR and RAD (P = 0.007 vs. LVA) (Fig. 2E) simultaneously in all hippocampal layers (4.6 ± 1.06 events/per delta epoch; with duration of 0.8 sec ± 0.14 sec) (Fig. 2 B–D).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataSpontaneous isolated spikes were observed in only 66% of mice after SE, not statistically different from controls.
“In addition to different patterns from MEA, spontaneous isolated spikes were observed in only 66% of mice after SE; however these were not statistically different from controls that showed similar spike profiles (P = 0.09 vs. control) (S1 Fig.).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataWithin MEA, high frequency activity is present associated with a peak of 120 Hz in all hippocampal layers and a trend of higher frequency bands in RAD.
“Also, within the MEA, high frequency activity was present associated with a peak of 120 Hz in all hippocampal layers and a trend of higher frequency bands in the RAD (Fig. 4B).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataMEA shows reduction of power in low frequency bands, especially delta and beta in OR and DG, compared with controls, and a trend of increased gamma waves in all layers.
“These MEA showed reduction of the power in the low frequency bands, especially in delta and beta in the OR and DG, compared with controls (Fig. 4A); a trend of increased gamma waves occurred in all layers observed.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationOmega-3 essential fatty acid improves neurological outcomes in models of epilepsy and is neuroprotective.
“Recent evidence suggests that omega-3 essential fatty acid improves neurological outcomes in models of epilepsy [14, 15] and is neuroprotective [12, 16, 17].”
Quote in the paperNot a substantial claim0 of 5 sources checked- cites [14] C Young, 2000, Docosahexaenoic acid inhibits synaptic transmission and epileptiform activity in the rat hippocampus, Synapse source
Not checked in the free run.
- cites [15] AE Musto, 2011, The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis, Epilepsia source
Not checked in the free run.
- cites [12] NG Bazan, 2011, Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases, Annu Rev Nutr source
Not checked in the free run.
- cites [16] NG Bazan, 2010, Rescue and repair during photoreceptor cell renewal mediated by docosahexaenoic acid-derived neuroprotectin D1, J Lipid Res source
Not checked in the free run.
- cites [17] L Belayev, 2009, Robust docosahexaenoic acid-mediated neuroprotection in a rat model of transient, focal cerebral ischemia, Stroke source
Not checked in the free run.
May combine two claims.
PremisecitationNPD1 promotes cell survival and homeostasis regulation during cellular damage.
“NPD1 promotes cell survival and homeostasis regulation during cellular damage [18].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] NG Bazan, 2012, Neuroinflammation
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNPD1 attenuates damage resulting from ischemia-reperfusion.
“The stereoselective mediator neuroprotectin D1 (NPD1; 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid) has been shown to attenuate damage resulting from ischemia-reperfusion [19].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] VL Marcheselli, 2003, Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression, J Biol Chem source
Not checked in the free run.
May combine two claims.
PremisecitationThere are no effective treatments or preventive/disease-modifying therapies for TLE or epileptogenesis.
“Aside from neurosurgical resection, which benefits only a small population of TLE patients [2], there are no other effective treatments or preventive strategies for TLE [3].”
- Also stated in: § Introduction · plain
“Unfortunately, there is no current effective treatment that prevents, or a disease-modifying therapy for epileptogenesis.”
Quote in the paperSubstantial claim0 of 2 sources checked- Also stated in: § Introduction · plain
Classified as probably not a substantial claim.
PremisecitationDHA-derived docosanoids mediate neuroprotective bioactivity.
“DHA-derived docosanoids mediate neuroprotective bioactivity [18].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] NG Bazan, 2012, Neuroinflammation
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationMost antiepileptic drugs act by inhibiting voltage-gated sodium or calcium channels or potentiating GABA-mediated synaptic transmission, resulting in a symptomatic approach.
“Although, there is an abundance of diverse antiepileptic drugs, most of them exert their actions by inhibition of the voltage-gated sodium or calcium channels or by potentiation of the GABA-mediated synaptic transmission [11], which results in a symptomatic approach in most cases; the goal of these drugs is to eliminate or at least reduce the number and/or severity of seizures.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] M Bialer, 2013, Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI), Epilepsy Res source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDHA is concentrated and avidly retained in phospholipids of synaptic and other neural membranes.
“Docosahexaenoic acid (DHA), an omega-3 essential fatty acid family member, is concentrated and avidly retained in phospholipids of synaptic and other neural membranes [12, 13].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [12] NG Bazan, 2011, Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer’s, and other neurodegenerative diseases, Annu Rev Nutr source
Not checked in the free run.
- cites [13] NG Bazan, 2011, Endogenous signaling by omega-3 docosahexaenoic acid-derived mediators sustains homeostatic synaptic and circuitry integrity, Mol Neurobiol source
Not checked in the free run.
May combine two claims.
PremisecitationSeizure progression severity and hippocampal hyperexcitability are attenuated upon intraventricular administration of NPD1.
“Moreover, seizure progression severity and hippocampal hyperexcitability are attenuated upon intraventricular administration of NPD1 [15].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] AE Musto, 2011, The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis, Epilepsia source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHippocampal hyper-excitability is a paroxysmal and self-limited neuronal network phenomenon characterized by the hyper-synchrony of a large population of neurons.
“Hippocampal hyper-excitability represents a paroxysmal and self-limited neuronal network phenomenon characterized by the hyper-synchrony of a large population of neurons [51]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [51] S Osawa, 2013, Optogenetically induced seizure and the longitudinal hippocampal network dynamics, PLoS One source
Not checked in the free run.
May combine two claims.
Study design and conductown dataThe number of samples and their duration between vehicle and NPD1-treated animals were not statistically significant.
“The number of samples and their duration between vehicle and NPD1-treated animals were not statistically significance (p = 0.2; p = 0.3 respectively).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataDelta epochs were selected by an investigator blinded to treatment.
“Then delta epochs (5–6 seconds each) (Fig. 2A) from each local field potential were determined by periods of immobility, without artifacts or noise, selected by an investigator blinded to the treatment, and confirmed by reproduction of video recordings and by calculating the ratio of delta and theta frequency bands in the CA1 hippocampal region [27].”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationThe pilocarpine model of temporal lobe epilepsy in adult mice shows an onset of recurrent spontaneous seizures 7 days after status epilepticus that can continue for at least 7 weeks.
“The pilocarpine model of TLE in adult mice shows an onset of recurrent spontaneous seizures 7 days after SE that can continue for at least 7 weeks [27, 34, 35].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [27] J Csicsvari, 1998, Reliability and state dependence of pyramidal cell-interneuron synapses in the hippocampus: an ensemble approach in the behaving rat, Neuron source
Not checked in the free run.
- cites [34] J Seo, 2012, Early deficits in social behavior and cortical rhythms in pilocarpine-induced mouse model of temporal lobe epilepsy, Exp Neurol S0014–4886
Not checked in the free run.
- cites [35] H Shibley, 2002, Pilocarpine-induced status epilepticus results in mossy fiber sprouting and spontaneous seizures in C57BL/6 and CD-1 mice, Epilepsy Res source
Not checked in the free run.
May combine two claims.
PremisecitationAfter intra-ventricular administration of NPD1 during kindling epileptogenesis, NPD1 limits progression of seizure severity and hippocampal hyper-excitability, including abnormal patterns of the electrical seizures.
“After intra-ventricular administration of NPD1 during kindling epileptogenesis, we observed that NPD1 limits progression of seizure severity and hippocampal hyper-excitability, including abnormal patterns of the electrical seizures [15]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] AE Musto, 2011, The omega-3 fatty acid-derived neuroprotectin D1 limits hippocampal hyperexcitability and seizure susceptibility in kindling epileptogenesis, Epilepsia source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductcitationHistological verification of probe placement in the dorsal hippocampus was confirmed by histology.
“At the end of the experiment, histological verification of probe placement in the dorsal hippocampus was confirmed by histology [29] for anatomic-physiological correlation of different hippocampal layers [21].”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenEach group had an equal number of analyzed dendrites.
“Each group had an equal number of analyzed dendrites.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown dataStudies were performed according to National Institutes of Health and ARRIVE guidelines and IACUC approved protocols.
“Studies were performed according to National Institutes of Health and ARRIVE guidelines and in accordance with nationally accepted principles in the care and use of experimental animals. The Institutional Animal Care and Use Committee (IACUC) at the Louisiana State University Health Sciences Center (LSUHSC), New Orleans, approved the animal protocols used for this study.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAnimals were randomized to treatment groups.
“Then surviving animals (n = 45, 60%) were randomized and placed in individual cages until surgery and/or further treatment (Fig. 1A).”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationDendritic spines are a morphological signature of post-synaptic sites.
“dendritic spines are thought to be a morphological signature of post-synaptic sites [36]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] R Yuste, 2011, Dendritic spines and distributed circuits, Neuron source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataDendritic spine analysis was done by investigators blinded to experimental conditions.
“Analysis of the number of dendritic spines was done using Image J software (National Institute of Health) by investigators blinded to the experimental conditions.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationBDNF, NGF, NT3 and other neurotrophins are NPD1-synthesis agonists.
“since BDNF, NGF, NT3 and other neurotrophins are NPD1-synthesis agonists”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [57] PK Mukherjee, 2007, Neurotrophins enhance retinal pigment epithelial cell survival through neuroprotectin D1 signaling, Proc Natl Acad Sci USA source
Not checked in the free run.
May combine two claims.
PremisecitationNPD1 modulates neuroinflammatory signaling and reduces oxidative stress-induced apoptosis by modulating pro-inflammatory gene expression and the Bcl-2 family of proteins.
“NPD1 modulates neuroinflammatory signaling and reduces oxidative stress-induced apoptosis by modulating pro-inflammatory gene expression and the Bcl-2 family of proteins [18, 56].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [18] NG Bazan, 2012, Neuroinflammation
Not checked in the free run.
- cites [56] NG Bazan, 2012, Lipid mediators: Eicosanoids, docosanoids and platelet-activating factor
Not checked in the free run.
May combine two claims.
Interpretationown dataHippocampal hyper-excitability could be initiated by bursts of pathological high-frequency oscillations and modulated by NPD1, resulting in decreased MEA.
“that could be initiated by bursts of pHFO and modulated by NPD1 resulting in decreased MEA (Fig. 5).”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningNPD1 administration could initiate or strengthen endogenous neuroprotective signaling in dendritic spines and limit their damage.
“Therefore, NPD1 administration could also initiate or strengthen endogenous neuroprotective signaling in dendritic spines and limit their damage.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEpileptiform activity during initiation of epileptic discharges in the neocortex suggests enhanced postsynaptic activity.
“Epileptiform activity during initiation of epileptic discharges in the neocortex [52] suggests enhanced postsynaptic activity [53].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [52] AB Chatt, 1982, The laminar sensitivity of cat striate cortex to penicillin induced epileptogenesis, Brain Res source
Not checked in the free run.
- cites [53] R Galvez, 2006, Vibrissa-signaled eyeblink conditioning induces somatosensory cortical plasticity, J Neurosci source
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationLocal field potentials represent post-synaptic potential activities from synchronized neurons.
“Because LFPs represent post-synaptic potential activities from synchronized neurons [21]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] G Buzsáki, 2003, Hippocampal network patterns of activity in the mouse, Neuroscience source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationcitationDendritic spine rearrangement could result from seizure-induced dendritic spine loss.
“Moreover, dendritic spine rearrangement could result from seizure-induced dendritic spine loss [55].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [55] MP Mattson, 1999, “Apoptotic” biochemical cascades in synaptic compartments: roles in adaptive plasticity and neurodegenerative disorders, J Neurosci Res source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone givenSeizure quantification was performed by an investigator blinded to treatment.
“Then the number of spontaneous motor seizures (stage 3 or and 4), according to the Racine’s score [25], and their durations were quantified each day (5–6 hours) by an investigator blinded to the treatment, and then the total number of those seizures was summarized for each animal.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDendritic swelling and beading are hallmarks of dendritic injury.
“dendritic swelling and beading, both of which are hallmarks of dendritic injury [38]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [38] X Gao, 2011, Moderate traumatic brain injury causes acute dendritic and synaptic degeneration in the hippocampal dentate gyrus, PLoS One source
Not checked in the free run.
May combine two claims.
Interpretationown dataNPD1 provides effective neuroprotection that down-regulates epileptogenesis and rescues vulnerable cellular and sub-cellular structures after status epilepticus.
“our studies here show that NPD1 provides effective neuroprotection that down-regulates epileptogenesis and rescues vulnerable cellular and sub-cellular structures after SE.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationNPD1 could downregulate cyclooxygenase-2 expression during epileptogenesis and limit neuroinflammatory-mediated damage.
“In addition, it could downregulate cyclooxgenase-2 expression during epileptogenesis [58] and limit neuroinflammatory-mediated damage [19, 56].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [58] B Tu, 2003, Hippocampal kindling epileptogenesis upregulates neuronal cyclooxygenase-2 expression in neocortex, Exp Neurol
Not checked in the free run.
- cites [19] VL Marcheselli, 2003, Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression, J Biol Chem source
Not checked in the free run.
- cites [56] NG Bazan, 2012, Lipid mediators: Eicosanoids, docosanoids and platelet-activating factor
Not checked in the free run.
The paper relies on this without support.
NPD1 administered intraperitoneally at 570 μg/kg for five consecutive days reaches the hippocampus and engages neuroprotective signaling.
“NPD1 and vehicle solutions were prepared according to previous protocols [30], and then NPD1 (570 μg/kg) or vehicle was administered i.p. once a day for five consecutive days 24 hours after termination of SE.”
The paper relies on this without support.
Dendritic spine number measured by Golgi staining is a valid proxy for synaptic integrity and network function.
“Then the number of dendritic spines (irrespective of their morphological characteristics that emerged perpendicular from the dendritic shaft) for each segment of the dendrite (10 μm) was quantified according to established procedures using Image J software (National Institute of Health) [31].”
The paper relies on this without support.
The vehicle solution is inert and does not affect hippocampal networks or seizures.
“NPD1 (570 μg/kg) or vehicle was administered intraperitoneally daily for five consecutive days 24 hours after termination of SE.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NPD1 rescues neuronal network disruptions, and this bioactivity may help identify critical events in the onset of pathological circuit impairments including epileptogenesis.
“Thus, NPD1 rescues neuronal networks disruptions and this bioactivity may help contribute to identifying critical events in the onset of pathological circuit impairments including epileptogenesis (Bazan et al., 2011b; Musto et al., 2015, 2016).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Musto et al., 2015
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Survival percentage does not match the reported mouse counts
MinorThe methods report 52 mice receiving pilocarpine and 45 surviving. That is 86.5%, not 60%.
Reported 60 · recomputed 86.538462
“Then surviving animals (n = 45, 60%) were randomized”
Cites
Modification of seizure activity by electrical stimulation: II. Motor seizure
Racine, R. J. (1972) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(72)90177-0 · Cited by 7,141 · see citing works
Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations
Klausberger, T., & Somogyi, P. (2008) · Science · doi:10.1126/science.1149381 · Cited by 2,050 · see citing works
Early Surgical Therapy for Drug-Resistant Temporal Lobe Epilepsy
Engel, J. (2012) · JAMA · doi:10.1001/jama.2012.220 · Cited by 1,237 · see citing works
Marcheselli, V. L., Hong, S., Lukiw, W. J., Tian, X. H., Gronert, K., Musto, A., Hardy, M., Gimenez, J. M., Chiang, N., Serhan, C. N., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305841200 · Cited by 802 · see citing works
Self-citationReliability and State Dependence of Pyramidal Cell–Interneuron Synapses in the Hippocampus
Csicsvari, J., Hirase, H., Czurko, A., & Buzsáki, G. (1998) · Neuron · doi:10.1016/s0896-6273(00)80525-5 · Cited by 606 · see citing works
Hippocampal network patterns of activity in the mouse
Buzsáki, G., Buhl, D. L., Harris, K. D., Csicsvari, J., Czéh, B., & Morozov, A. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00669-3 · Cited by 486 · see citing works
Bazan, N. G., Molina, M. F., & Gordon, W. C. (2011) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.012809.104635 · Cited by 441 · see citing works
Self-citationLocally synchronized synaptic inputs
Takahashi, N., Kitamura, K., Matsuo, N., Mayford, M., Kano, M., Matsuki, N., & Ikegaya, Y. (2012) · Science · doi:10.1126/science.1210362 · Cited by 352 · see citing works
Modular Propagation of Epileptiform Activity: Evidence for an Inhibitory Veto in Neocortex
Trevelyan, A. J., Sussillo, D., Watson, B. O., & Yuste, R. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.2787-06.2006 · Cited by 344 · see citing works
Microseizures and the spatiotemporal scales of human partial epilepsy
Stead, M., Bower, M. R., Brinkmann, B. H., Lee, K. H., Marsh, W. R., Meyer, F. B., Litt, B., Gompel, J. J. V., & Worrell, G. A. (2010) · Brain · doi:10.1093/brain/awq190 · Cited by 311 · see citing works
Dendritic spines and distributed circuits
Yuste, R. (2011) · Neuron · doi:10.1016/j.neuron.2011.07.024 · Cited by 298 · see citing works
Progress report on new antiepileptic drugs: a summary of the Eleventh Eilat Conference (EILAT XI)
Bialer, M., Johannessen, S. I., Levy, R. H., Perucca, E., Tomson, T., & White, H. S. (2013) · Epilepsy Research · doi:10.1016/j.eplepsyres.2012.10.001 · Cited by 243 · see citing works
Gao, X., Deng, P., Xu, Z. C., & Chen, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024566 · Cited by 218 · see citing works
Dinocourt, C., Petanjek, Z., Freund, T. F., Ben‐Ari, Y., & Esclapez, M. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10622 · Cited by 208 · see citing works
Shibley, H., & Smith, B. N. (2002) · Epilepsy Research · doi:10.1016/s0920-1211(02)00012-8 · Cited by 201 · see citing works
Barros, C. S., Calabrese, B., Chamero, P., Roberts, A. J., Korzus, E., Lloyd, K., Stowers, L., Mayford, M., Halpain, S., & Müller, U. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900355106 · Cited by 197 · see citing works
André, V., Marescaux, C., Nehlig, A., & Fritschy, J. (2001) · Hippocampus · doi:10.1002/hipo.1060 · Cited by 192 · see citing works
Neurotrophins enhance retinal pigment epithelial cell survival through neuroprotectin D1 signaling
Mukherjee, P. K., Marcheselli, V. L., Barreiro, S., Hu, J., Bok, D., & Bazan, N. G. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705949104 · Cited by 170 · see citing works
Self-citationBelayev, L., Khoutorova, L., Atkins, K. D., & Bazan, N. G. (2009) · Stroke · doi:10.1161/strokeaha.109.555979 · Cited by 170 · see citing works
Self-citationJiang, J., Quan, Y., Ganesh, T., Pouliot, W. A., Dudek, F. E., & Dingledine, R. J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218498110 · Cited by 167 · see citing works
Microphysiology of Epileptiform Activity in Human Neocortex
Schevon, C. A., Ng, S. K., Cappell, J., Goodman, R. R., McKhann, G. M., Waziri, A. E., Branner, A., Sosunov, A. A., Schroeder, C. E., & Emerson, R. G. (2008) · Journal of Clinical Neurophysiology · doi:10.1097/wnp.0b013e31818e8010 · Cited by 162 · see citing works
Muldoon, S. F., Soltész, I., & Cossart, R. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216958110 · Cited by 162 · see citing works
Bazan, N. G., Calandria, J. M., & Serhan, C. N. (2010) · Journal of Lipid Research · doi:10.1194/jlr.r001131 · Cited by 140 · see citing works
Bragin, A., Benassi, S. K., Kheiri, F., & Engel, J. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2010.02896.x · Cited by 135 · see citing works
Nrf2 defense pathway: Experimental evidence for its protective role in epilepsy
Mazzuferi, M., Kumar, G., van Eyll, J. M., Danis, B., Foerch, P., & Kaminski, R. M. (2013) · Annals of Neurology · doi:10.1002/ana.23940 · Cited by 132 · see citing works
Timofeev, I., Grenier, F., & Steriade, M. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00300-7 · Cited by 125 · see citing works
Bazan, N. G., Musto, A. E., & Knott, E. J. (2011) · Molecular Neurobiology · doi:10.1007/s12035-011-8200-6 · Cited by 125 · see citing works
Self-citationNeuronal circuits in epilepsy: do they matter?
Bertram, E. H. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2012.01.028 · Cited by 112 · see citing works
Tu, B., & Bazan, N. G. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(02)00019-5 · Cited by 108 · see citing works
Self-citationDifferential vulnerability of interneurons in the epileptic hippocampus
Marx, M., Haas, C. A., & Häussler, U. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00167 · Cited by 104 · see citing works
Grabenstatter, H., Angel, Y. C. D., Carlsen, J., Wempe, M., White, A. M., Cogswell, M., Russek, S., & Brooks-Kayal, A. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.09.003 · Cited by 104 · see citing works
Large-scale Recording of Neurons by Movable Silicon Probes in Behaving Rodents
Vandecasteele, M., M., S., Royer, S., Belluscio, M., Berényi, A., Diba, K., Fujisawa, S., Grosmark, A., Mao, D., Mizuseki, K., et al. (2012) · Journal of Visualized Experiments · doi:10.3791/3568 · Cited by 99 · see citing works
Sloviter, R. S., & Bumanglag, A. V. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.01.022 · Cited by 97 · see citing works
Optogenetically induced seizure and the longitudinal hippocampal network dynamics
Osawa, S.-I., Iwasaki, M., Hosaka, R., Matsuzaka, Y., Tomita, H., Ishizuka, T., Sugano, E., Okumura, E., Yawo, H., Nakasato, N., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060928 · Cited by 96 · see citing works
Emerging Concepts in the Pathogenesis of Epilepsy and Epileptogenesis
Dichter, M. A. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.10 · Cited by 91 · see citing works
Musto, A. E., Gjorstrup, P., & Bazan, N. G. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03081.x · Cited by 71 · see citing works
Vibrissa-signaled eyeblink conditioning induces somatosensory cortical plasticity
Galvez, R., Weiss, C., Weible, A. P., & Disterhoft, J. F. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.5582-05.2006 · Cited by 66 · see citing works
Update on the surgical treatment of epilepsy
Jette, N., & Wiebe, S. (2013) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32835ef345 · Cited by 56 · see citing works
Human clinical trails in antiepileptogenesis
Mani, R., Pollard, J., & Dichter, M. A. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.03.010 · Cited by 51 · see citing works
Network mechanisms for fast ripple activity in epileptic tissue
Köhling, R., & Staley, K. J. (2011) · Epilepsy Research · doi:10.1016/j.eplepsyres.2011.03.006 · Cited by 50 · see citing works
A cellular mechanism for dendritic spine loss in the pilocarpine model of status epilepticus
Kurz, J. E., Moore, B. J., Henderson, S. C., Campbell, J. N., & Churn, S. B. (2008) · Epilepsia · doi:10.1111/j.1528-1167.2008.01616.x · Cited by 48 · cited 1× · see citing works
“Because LFPs represent post-synaptic potential activities from synchronized neurons [21], and since dendritic spines are thought to be a morphological signature of post-synaptic sites [36] and a key target for neuronal network assemblies damaged during epilepsy [37], we asked whether MEAs were associated with hippocam…”
BackgroundChen, J., Larionov, S., Pitsch, J., Hoerold, N., Ullmann, C., Elger, C. E., Schramm, J., & Becker, A. J. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.11.008 · Cited by 48 · see citing works
McAuliffe, J. J., Bronson, S. L., Hester, M. S., Murphy, B. L., Dahlquist‐Topalá, R., Richards, D. A., & Danzer, S. C. (2011) · Hippocampus · doi:10.1002/hipo.20726 · Cited by 47 · see citing works
The laminar sensitivity of cat striate cortex to penicillin induced epileptogenesis
Chatt, A. B., & Ebersole, J. S. (1982) · Brain Research · doi:10.1016/0006-8993(82)91084-8 · Cited by 45 · see citing works
Neuroprotectin D1 attenuates laser-induced choroidal neovascularization in mouse.
Sheets, K. G., Zhou, Y., Ertel, M. K., Knott, E. J., Regan, C. E., Elison, J. R., Gordon, W. C., Gjorstrup, P., & Bazan, N. G. (2010) · PubMed Central · Cited by 40 · see citing works
Self-citationMolecular biomarkers of epileptogenesis
Pitkänen, A., & Lukasiuk, K. (2011) · Biomarkers in Medicine · doi:10.2217/bmm.11.67 · Cited by 40 · see citing works
Different phases of afterdischarge during rapid kindling procedure in mice
Musto, A. E., Samii, M. S., & Hayes, J. F. (2009) · Epilepsy Research · doi:10.1016/j.eplepsyres.2009.02.020 · Cited by 35 · see citing works
Self-citationRusan, Z. M., Kingsford, O. A., & Tanouye, M. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101117 · Cited by 32 · see citing works
Large-scale Recording of Neurons by Movable Silicon Probes in Behaving Rodents
Vandecasteele, M., M., S., Royer, S., et al. (2012) · Journal of Visualized Experiments · doi:10.3791/3568-v · Cited by 32 · see citing works
Soussi, R., Boulland, J., Bassot, E., Bras, H., Coulon, P., Chaudhry, F. A., Storm‐Mathisen, J., Ferhat, L., & Esclapez, M. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0800-2 · Cited by 31 · see citing works
Seo, J., Jung, S., Lee, S., Yang, H. J., Kim, B. S., Choi, J., Bang, M., Shin, H., & Jeon, D. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2012.11.024 · Cited by 29 · see citing works
Danzer, E., Finkel, R., Gerdes, M., Schwartz, E. M. S., Rintoul, N., Adzick, N., & Johnson, M. (2010) · Neuropediatrics · doi:10.1055/s-0030-1263164 · Cited by 25 · see citing works
Dudek, F. E., & Staley, K. J. (2011) · Epilepsy Research · doi:10.1016/j.eplepsyres.2011.10.017 · Cited by 20 · see citing works
Helgager, J., Liu, G., & McNamara, J. O. (2013) · Journal of Comparative Neurology · doi:10.1002/cne.23225 · Cited by 17 · see citing works
Combined process automation for large-scale EEG analysis
Sfondouris, J. L., Quebedeaux, T. M., Holdgraf, C., et al. (2011) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2011.10.017 · Cited by 12 · see citing works
Bazan, N. G., Stark, D. T., & Petasis, N. A. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-374947-5.00036-5 · Cited by 5 · see citing works
Self-citationAndré, V., Marescaux, C., Nehlig, A., et al. (2001) · Hippocampus · doi:10.1002/hipo.1060.abs · Cited by 4 · see citing works
Mattson, M. (1999) · doi:10.1002/(sici)1097-4547(19991001)58:1
Andersen (2000) · doi:10.1002/1098-2396(200008)37:2
Flagged first, then by citations
Research works printed but not linked: 1
- B Tu, 2003, Hippocampal kindling epileptogenesis upregulates neuronal cyclooxygenase-2 expression in neocortex, Exp Neurol, 179, 167
Cited by
Sorted by citations
Bazan, N. G. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.09.003 · Cited by 148 · see citing works
Self-citation
- Authors
- Musto, A. E., Walker, C. P., Petasis, N. A., & Bazan, N. G.
- Affiliations
- Louisiana State University Health Sciences Center New Orleans (US)
- University of Southern California (US)
- Corresponding author
- Musto, Alberto E.
- Bazan, Nicolas G.
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2015-01-24
- Volume
- 10
- Issue
- 1
- Pages
- e0116543
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4305283
- OpenAlex
- W2062037597
- Semantic Scholar
- da7a0c3cd66abab6f67d936108477b952f30a3c0
- Cited by
- 39
- References
- 59
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 7 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 2
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (GM-103340)
- National Institute of General Medical Sciences (GM-103340, P30GM103340)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Keywords
- neuroprotectin D1, epileptogenesis, limbic epilepsy, temporal lobe epilepsy, status epilepticus, pilocarpine, dendritic spines, docosahexaenoic acid, lipid mediators, spontaneous seizures
- MeSH terms
- Animals, Docosahexaenoic Acids, Epilepsy, Temporal Lobe, Hippocampus, Limbic System, Male, Mice, Inbred C57BL, Nerve Net, Pilocarpine, Status Epilepticus, Dendritic Spines, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
