The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders

In the paper

“For example, high levels of brevican mRNA expression were detected in postmortem human cortex during early development until 8 years of age, and the expression levels were lower in the adult human brain (Gary et al., 2000).”

What the sources say

• Supported

  Figure 4 in Section 3.2 reports RNase protection analysis of RNA from normal human cortex. It states that BEHAB/brevican levels are high from birth through age 8, fall by age 20, and remain low throughout adulthood. (LLM, conf=0.94)

  cites Gary et al., 2000 source

In the paper

“Studies of postmortem human tissues also suggest developmental changes in lectican levels in human CNS.”

In the paper

“In contrast, the expression of beta isoform increased 2–3 fold from embryonic day (E) 14 until birth and then decreased in adulthood.”

In the paper

“In parallel, a number of these CNS diseases exhibit dysregulated expression of enzymes necessary for PNN cleavage and reorganization (Backstrom et al., 1996; Lorenzl et al., 2003; Rybakowski et al., 2009; Kim et al., 2009; Zhang et al., 2011; Yamamori et al., 2013; Liu et al., 2014; Rankin-Gee et al., 2015; Lepeta et al., 2017).”

What the sources say

• Not checked yetcites Backstrom et al., 1996 source
• Not checked yetcites Lorenzl et al., 2003 source
• Not checked yetcites Rybakowski et al., 2009 source

In the paper

“There is impaired development of PNNs and enhanced activity of its key regulator matrix metalloproteinase-9 (MMP-9) in Fragile X Syndrome, a common genetic cause of autism.”

In the paper

“Neurocan expression also increased between E14 and postnatal day (P) 3 and then decreased during early-late adolescence and into adulthood (Meyer-Puttlitz et al., 1996; Miller et al., 1996; Milev et al., 1998; Brückner et al., 2000).”

What the sources say

• Not checked yetcites Meyer-Puttlitz et al., 1996 source
• Not checked yetcites Miller et al., 1996 source
• Not checked yetcites Milev et al., 1998 source

In the paper

“MMP-9, a protease that cleaves ECM, is differentially regulated in a number of these disorders.”

In the paper

“Indeed, PNN abnormalities have been observed in post-mortem brain tissues of patients with schizophrenia and Alzheimer’s disease.”

In the paper

“A developmental upregulation of aggrecan and brevican, which peak in adulthood, was reported in rat brain (Milev et al., 1998; Brückner et al., 2000; Popp et al., 2003).”

What the sources say

• Not checked yetcites Milev et al., 1998 source
• Not checked yetcites Brückner et al., 2000 source
• Not checked yetcites Popp et al., 2003 source

In the paper

“The expression of alpha isoform was low during embryonic development, first and second postnatal weeks, and then increased steadily until around 3.5 months of age (Bignami et al., 1993b).”

What the sources say

• Not checked yetcites Bignami et al., 1993b

In the paper

“There is impaired development of PNNs and enhanced activity of its key regulator matrix metalloproteinase-9 (MMP-9) in Fragile X Syndrome, a common genetic cause of autism.”

In the paper

“A recent study by Murase and colleagues demonstrated that PV, PNN, and MMP-9 interactions are important for driving adult plasticity (Murase et al., 2017).”

What the sources say

• Not checked yetcites Murase et al., 2017 source

In the paper

“Astrocytes extend their processes into PNNs localized near the synapse (Brückner et al., 1993; Blümcke et al., 1995), suggesting a tetrapartite synaptic organization involving ECM, pre/post synaptic sites and astrocytes (Dityatev and Rusakov, 2011; Smith et al., 2015) whose synergistic functions remain unexplored.”

What the sources say

• Not checked yetcites Brückner et al., 1993 source
• Not checked yetcites Blümcke et al., 1995 source

In the paper

“Studies comparing PNNs detected with lectins or specific antibodies indicate substantial levels of molecular heterogeneity (Matthews et al., 2002; Irvine and Kwok, 2018), highlighting the need for better approaches which address PNN heterogeneity (Irvine and Kwok, 2018).”

What the sources say

• Not checked yetcites Matthews et al., 2002 source
• Not checked yetcites Irvine and Kwok, 2018

In the paper

“In fact, PV and PNN colocalization is correlated with critical period closure and reduced synaptic plasticity, particularly in sensory cortices (Nowicka et al., 2009; Beurdeley et al., 2012).”

What the sources say

• Not checked yetcites Nowicka et al., 2009 source
• Not checked yetcites Beurdeley et al., 2012 source

In the paper

“Auditory hypersensitivity is common in humans with FXS as measured by increased sound evoked responses, reduced habituation and expansion of brain regions activated by auditory stimuli (Rojas et al., 2001; Castrén et al., 2003; Van der Molen et al., 2012; Ethridge et al., 2016).”

What the sources say

• Not checked yetcites Rojas et al., 2001 source
• Not checked yetcites Castrén et al., 2003 source
• Not checked yetcites Van der Molen et al., 2012 source

In the paper

“Interestingly, developing auditory cortex appears to exhibit fewer PNN and PV expressing cells than visual or somatosensory cortex, but in adult sensory cortices, a majority of PV cells express PNNs as seen with WFA staining.”

In the paper

“Otx2 expression coincides with both PV and PNN expression in the cortex during critical period plasticity (Sugiyama et al., 2008).”

What the sources say

• Not checked yetcites Sugiyama et al., 2008 source

In the paper

“In vivo electrophysiological studies demonstrate that neurons in adult Fmr1 KO mouse auditory cortex (1) are hyperexcitable, exhibiting increased responses per stimulus, (2) show more variable response latencies, and (3) display broader frequency tuning curves (Rotschafer and Razak, 2013).”

What the sources say

• Not checked yetcites Rotschafer and Razak, 2013

In the paper

“In vivo electrophysiological studies demonstrate that neurons in adult Fmr1 KO mouse auditory cortex (1) are hyperexcitable, exhibiting increased responses per stimulus, (2) show more variable response latencies, and (3) display broader frequency tuning curves (Rotschafer and Razak, 2013).”

What the sources say

• Not checked yetcites Rotschafer and Razak, 2013

In the paper

“Recent work using EEG/ERP recordings shows that mature Fmr1 KO mouse auditory cortex exhibits reduced habituation to repeated sound presentations (Lovelace et al., 2016).”

What the sources say

• Not checked yetcites Lovelace et al., 2016 source

In the paper

“When resting EEG is analyzed for spectral power distribution, Fmr1 KO mouse cortex shows increased gamma power.”

In the paper

“We found delayed PNN development and increased MMP-9 activity levels in the developing auditory cortex of Fmr1 KO mice (Wen et al., 2017), which may lead to impaired PV cell development and reduced inhibition.”

What the sources say

• Not checked yetcites Wen et al., 2017 source

In the paper

“Minocycline administration in Fmr1 KO mice prevents abnormal dendritic spine development in the hippocampus, improves anxiety-like behaviors (Bilousova et al., 2009; Dansie et al., 2013) and corrects ultrasonic vocalizations (Rotschafer et al., 2012).”

What the sources say

• Not checked yetcites Rotschafer et al., 2012 source

In the paper

“PNNs are necessary for the uptake of Otx2 by PV cells, which promotes PV cell maturation (Beurdeley et al., 2012).”

What the sources say

• Not checked yetcites Beurdeley et al., 2012 source

In the paper

“In situ hybridization and RT-PCR studies indicate that post-mortem brain tissues from schizophrenia patients exhibit reduced PV and/or GAD67 mRNA, particularly in prefrontal cortex (Akbarian et al., 1995; Volk et al., 2000; Hashimoto et al., 2003, 2008a,b; Mellios et al., 2009).”

What the sources say

• Not checked yetcites Akbarian et al., 1995 source
• Not checked yetcites Volk et al., 2000 source
• Not checked yetcites Hashimoto et al., 2003 source

In the paper

“Minocycline administration in Fmr1 KO mice prevents abnormal dendritic spine development in the hippocampus, improves anxiety-like behaviors (Bilousova et al., 2009; Dansie et al., 2013) and corrects ultrasonic vocalizations (Rotschafer et al., 2012).”

What the sources say

• Not checked yetcites Bilousova et al., 2009 source
• Not checked yetcites Dansie et al., 2013 source

In the paper

“The somatosensory cortex of adult FXS mice exhibit delayed PV cell maturation (Nomura et al., 2017).”

What the sources say

• Not checked yetcites Nomura et al., 2017 source

In the paper

“In developing mice, PV interneurons receive reduced excitatory drive from neighboring pyramidal cells in layer 4 of somatosensory cortex (Gibson et al., 2008).”

What the sources say

• Not checked yetcites Gibson et al., 2008 source

In the paper

“Reduction of MMP-9 levels with minocycline in humans with FXS (Dziembowska et al., 2013) contributes to reversal of several FXS phenotypes, including behavioral deficits and enhanced auditory electrocortical activity in adults and/or adolescents with FXS (Paribello et al., 2010; Leigh et al., 2013; Schneider et al., 2013).”

What the sources say

• Not checked yetcites Dziembowska et al., 2013 source
• Not checked yetcites Paribello et al., 2010 source
• Not checked yetcites Leigh et al., 2013 source

In the paper

“Minocycline administration in Fmr1 KO mice prevents abnormal dendritic spine development in the hippocampus, improves anxiety-like behaviors (Bilousova et al., 2009; Dansie et al., 2013) and corrects ultrasonic vocalizations (Rotschafer et al., 2012).”

What the sources say

• Not checked yetcites Bilousova et al., 2009 source
• Not checked yetcites Dansie et al., 2013 source

In the paper

“In vivo electrophysiological studies demonstrate that neurons in adult Fmr1 KO mouse auditory cortex (1) are hyperexcitable, exhibiting increased responses per stimulus, (2) show more variable response latencies, and (3) display broader frequency tuning curves (Rotschafer and Razak, 2013).”

What the sources say

• Not checked yetcites Rotschafer and Razak, 2013

In the paper

“We found delayed PNN development and increased MMP-9 activity levels in the developing auditory cortex of Fmr1 KO mice (Wen et al., 2017), which may lead to impaired PV cell development and reduced inhibition.”

What the sources say

• Not checked yetcites Wen et al., 2017 source

In the paper

“Analysis of post-mortem human brain tissues demonstrated reduced PV cell density and immunoreactivity at epileptic foci in the hippocampus and neocortex (Sloviter et al., 1991; Ferrer et al., 1994; Andrioli et al., 2007).”

What the sources say

• Not checked yetcites Sloviter et al., 1991 source
• Not checked yetcites Ferrer et al., 1994 source
• Not checked yetcites Andrioli et al., 2007 source

In the paper

“For example, network oscillatory activity that was increased by drug-induced changes in dopaminergic signaling in mouse prefrontal cortex was further enhanced following chABC-mediated degradation of PNNs (Steullet et al., 2014).”

What the sources say

• Not checked yetcites Steullet et al., 2014 source

In the paper

“In addition, brevican conditional knockdown in PV-expressing cells demonstrated that changes in the expression of specific lecticans alter synaptic input and firing frequency in PV cells (Favuzzi et al., 2017).”

What the sources say

• Not checked yetcites Favuzzi et al., 2017 source

In the paper

“Specifically, in vitro studies conducted in human neuroblastoma SH-SY5Y cells indicate that chondroitin sulfate application prior to exposure to oxidative-stress inducing agents, such as hydrogen peroxide, can prevent cell death and attenuate the production of reactive oxygen species.”

In the paper

“Genetic analysis of single nucleotide polymorphisms in schizophrenia patients demonstrates mutations in the gene encoding GCL, an enzyme that is important for the production of the cellular antioxidant GSH (Tosic et al., 2006).”

What the sources say

• Not checked yetcites Tosic et al., 2006 source

In the paper

“Reduced PV and GAD67 protein levels are also seen in both prefrontal and temporal cortex of post-mortem brain tissues (Beasley and Reynolds, 1997; Curley et al., 2011; Glausier et al., 2014).”

What the sources say

• Not checked yetcites Beasley and Reynolds, 1997 source
• Not checked yetcites Curley et al., 2011 source
• Not checked yetcites Glausier et al., 2014 source

In the paper

“A mouse model of schizophrenia also exhibits reduced PNN levels in prefrontal cortex (Cabungcal et al., 2014).”

What the sources say

• Not checked yetcites Cabungcal et al., 2014 source

In the paper

“During development, GCL KO mice had fewer PNN-expressing PV cells in anterior cingulate cortex, and the injection of a dopamine reuptake inhibitor to promote more oxidative stress via buildup of reactive oxygen species contributed to increased 8-oxo-dG signal and PV cell loss.”

In the paper

“Various clinical trials have been conducted using minocycline alone or as an adjunct to risperidone in patients with schizophrenia and have demonstrated overall improvement in negative symptoms and executive functioning (Miyaoka et al., 2008; Levkovitz et al., 2010; Khodaie-Ardakani et al., 2014).”

What the sources say

• Not checked yetcites Miyaoka et al., 2008 source
• Not checked yetcites Levkovitz et al., 2010 source
• Not checked yetcites Khodaie-Ardakani et al., 2014 source

In the paper

“Increased gamma-band power was observed in baseline EEG recordings from humans with schizophrenia (Gandal et al., 2012).”

What the sources say

• Not checked yetcites Gandal et al., 2012 source

In the paper

“A functional polymorphism of the MMP-9 gene was discovered in human schizophrenia patients (Rybakowski et al., 2009; Lepeta et al., 2017).”

What the sources say

• Not checked yetcites Rybakowski et al., 2009 source
• Not checked yetcites Lepeta et al., 2017 source

In the paper

“Additionally, Yamamori et al. (2013) showed elevated MMP-9 levels in the plasma of schizophrenic patients.”

What the sources say

• Not checked yetcites Yamamori et al. (2013) source

In the paper

“Indeed, several studies indicate that schizophrenia is associated with the loss of PNNs.”

In the paper

“During development, GCL KO mice had fewer PNN-expressing PV cells in anterior cingulate cortex, and the injection of a dopamine reuptake inhibitor to promote more oxidative stress via buildup of reactive oxygen species contributed to increased 8-oxo-dG signal and PV cell loss.”

In the paper

“In this model, schizophrenia-like abnormalities are reported in the adult mouse prefrontal cortex as a result of neonatal lesion of ventral hippocampus.”

In the paper

“Genomic sequencing data indicate that a number of mutations in the Scn1a gene contribute to a spectrum of different epileptic disorders affecting children, including de novo (Claes et al., 2001; Fujiwara et al., 2003) as well as missense, frame-shift, and nonsense mutations (Fujiwara et al., 2003).”

What the sources say

• Not checked yetcites Claes et al., 2001 source
• Not checked yetcites Fujiwara et al., 2003 source

In the paper

“For example, PV KO mice are more likely to experience status epilepticus compared to controls following increased doses of pentylenetetrazol (PTZ), a GABAA receptor blocker (Schwaller et al., 2004).”

What the sources say

• Not checked yetcites Schwaller et al., 2004 source

In the paper

“In the forebrain, PNNs are often found on PV expressing GABAergic neurons (Table 1).”

What the sources say

• Not checked yetcites Table 1

In the paper

“This complex of hyaluronan with ECM proteins forms the basis for PNN structure.”

In the paper

“Recently, increasing evidence suggests that PNNs are altered in various neurodevelopmental and neurodegenerative disorders associated with changes in brain activity (De Luca and Papa, 2016; Sorg et al., 2016; Härtig et al., 2016).”

What the sources say

• Not checked yetcites De Luca and Papa, 2016
• Not checked yetcites Sorg et al., 2016 source
• Not checked yetcites Härtig et al., 2016 source

In the paper

“Converging evidence indicates that PV cells and PNN are impaired in a variety of neurological disorders.”

In the paper

“Hyaluronan binds to other ECM molecules via N-terminal hyaluronan binding domains, including lecticans and link proteins such as cartilage link protein, Ctrl1, and brain-derived link proteins Bral1 and Bral2 (Frischknecht and Seidenbecher, 2008).”

What the sources say

• Not checked yetcites Frischknecht and Seidenbecher, 2008

In the paper

“PNN development and maintenance is necessary for a number of processes within the CNS, including regulation of GABAergic cell function, protection of neurons from oxidative stress, and closure of developmental critical period plasticity windows.”

In the paper

“Developmental regulation of ECM proteins, which make up PNNs, may underlie PNN formation, composition, and function (Köppe et al., 1997).”

What the sources say

• Not checked yetcites Köppe et al., 1997 source

In the paper

“These developmental changes in lectican expression levels suggest that the PNNs themselves may also be developmentally regulated, underlying maturation of circuit function (Köppe et al., 1997).”

What the sources say

• Not checked yetcites Köppe et al., 1997 source

In the paper

“Since then, PNNs have been implicated in a wide range of functions including neuroprotection, regulation of neural activity and experience-dependent plasticity.”

In the paper

“PNN development and maintenance is necessary for a number of processes within the CNS, including regulation of GABAergic cell function, protection of neurons from oxidative stress, and closure of developmental critical period plasticity windows.”

In the paper

“PNN development and maintenance is necessary for a number of processes within the CNS, including regulation of GABAergic cell function, protection of neurons from oxidative stress, and closure of developmental critical period plasticity windows.”

In the paper

“These auditory processing deficits may drive social, cognitive and language delays and deficits in FXS (Rotschafer and Razak, 2014; Sinclair et al., 2017a,b).”

What the sources say

• Not checked yetcites Rotschafer and Razak, 2014
• Not checked yetcites Sinclair et al., 2017a,b

In the paper

“As aggrecan has been previously identified as an MMP-9 target (Mercuri et al., 2000; Madsen et al., 2010; Rankin-Gee et al., 2015), aggrecan-rich PNNs may be unstable in the presence of MMP-9, leading to abnormal development and neural excitability (Murase et al., 2017; Wen et al., 2017).”

What the sources say

• Not checked yetcites Mercuri et al., 2000 source
• Not checked yetcites Madsen et al., 2010 source
• Not checked yetcites Rankin-Gee et al., 2015 source

In the paper

“PNNs may regulate PV cell functions (Hensch, 2005; Cabungcal et al., 2013; Bernard and Prochiantz, 2016), as PNN reorganization is shown to result in abnormal CNS development and altered neural excitability (Pizzorusso et al., 2002; Dityatev et al., 2007; Liu et al., 2013; Balmer, 2016; Lensjø et al., 2017).”

What the sources say

• Not checked yetcites Hensch, 2005 source
• Not checked yetcites Cabungcal et al., 2013 source
• Not checked yetcites Bernard and Prochiantz, 2016

In the paper

“Conversely, abnormal interactions may lead to neurological disorders.”

In the paper

“Cortical PV cells contribute to synchronous oscillatory activity (Cardin et al., 2009; Sohal et al., 2009; Uhlhaas et al., 2009), particularly in the gamma range (∼30–100 Hz).”

What the sources say

• Not checked yetcites Cardin et al., 2009 source
• Not checked yetcites Sohal et al., 2009 source
• Not checked yetcites Uhlhaas et al., 2009 source

In the paper

“High levels of MMP-9 contribute to proteolytic cleavage of ECM, creating an extracellular environment that is permissive for synaptic plasticity.”

In the paper

“Other cell types, including putative excitatory neurons also contain PNNs but they are less numerous compared to GABAergic-PNN expressing cells (Wegner et al., 2003).”

What the sources say

• Not checked yetcites Wegner et al., 2003 source

In the paper

“These findings suggest a link between PNNs, MMP-9 activity and PV activity that shapes normal brain development.”

In the paper

“Network excitability in FXS may also result from impaired synaptic scaling at PV cells due to PNN dysfunction.”

In the paper

“In addition to regulating cortical development, MMP-9 cleavage of PNNs may drive changes in PV expression and/or PV cell functions seen in FXS.”

In the paper

“There is evidence for a role of PNNs in mediating synaptic scaling via neuronal activity-regulated pentraxin, also known as Narp.”

In the paper

“Narp can interact with the N-terminal domain of AMPA receptors localized extracellularly and facilitate AMPA receptor clustering at both the pre- and post-synaptic cell in response to stimulation (O’Brien et al., 1999).”

What the sources say

• Not checked yetcites O’Brien et al., 1999 source

In the paper

“These data suggest that PNNs may drive PV cell maturation by directing transcription or translation of specific genes necessary for PV cell function.”

In the paper

“In FXS, delayed PNN expression around PV cells during development may contribute to abnormal PV cell maturation.”

In the paper

“These phenotypes in the mouse model are remarkably similar to those seen in humans with FXS (Castrén et al., 2003; Ethridge et al., 2016; Wang et al., 2017).”

What the sources say

• Not checked yetcites Castrén et al., 2003 source
• Not checked yetcites Ethridge et al., 2016 source
• Not checked yetcites Wang et al., 2017 source

In the paper

“PV cell maturation is characterized by gradual increases in signaling, including faster firing rates and IPSC kinetics (Lazarus and Huang, 2011).”

What the sources say

• Not checked yetcites Lazarus and Huang, 2011

In the paper

“These findings suggest that MMP-9-mediated cleavage of PNNs during development may underlie sensory hypersensitivity in FXS.”

In the paper

“Recent studies have hinted at the potential role of MMP-9 in the manifestation of schizophrenia phenotypes.”

In the paper

“The molecular mechanisms underlying seizure onset include impaired PV cell functions.”

In the paper

“As chABC removes GAG side chains from CSPGs (Bradbury et al., 2002), these results suggest that the neuroprotective effects of PNNs may be attributed to the CS-side chains of CSPGs.”

What the sources say

• Not checked yetcites Bradbury et al., 2002 source

In the paper

“PV cells are particularly susceptible to oxidative stress given their fast cellular metabolism and increased mitochondrial function (Hasenstaub et al., 2010; Kann et al., 2014; Inan et al., 2016).”

What the sources say

• Not checked yetcites Hasenstaub et al., 2010 source
• Not checked yetcites Kann et al., 2014 source
• Not checked yetcites Inan et al., 2016 source

In the paper

“These findings lend support to the idea that PNN composition plays an important role in regulating PV cell function.”

In the paper

“The effects of dysregulated dopamine signaling on prefrontal cortex oscillatory activity, which are suggested to drive schizophrenia phenotypes, can be also regulated by PNNs.”

In the paper

“As PNNs regulate GABAergic cell function and oxidative stress levels, cortical abnormalities observed in schizophrenia may be attributed to PNN dysfunction (reviewed in Berretta, 2012; Berretta et al., 2015).”

What the sources say

• Not checked yetcites Berretta, 2012 source
• Not checked yetcites Berretta et al., 2015 source

In the paper

“Cortical gamma band oscillations have been attributed to GABAergic cell activity, in particular PV interneurons (Sohal et al., 2009).”

What the sources say

• Not checked yetcites Sohal et al., 2009 source

In the paper

“These data suggest altered PV cell function in schizophrenia, but why these cells are susceptible is unclear.”

In the paper

“These results indicate that cells without PNNs are more susceptible to cell death (Morawski et al., 2004).”

What the sources say

• Not checked yetcites Morawski et al., 2004 source

In the paper

“Recent studies demonstrate that reduced PV cell spike output may contribute to seizures in mice with genetic knock-in of mutated human Scn1a, which results in subtle changes in Nav1.1 functionality (Ogiwara et al., 2007; Hedrich et al., 2014).”

What the sources say

• Not checked yetcites Ogiwara et al., 2007 source
• Not checked yetcites Hedrich et al., 2014 source

In the paper

“Post-mortem brains of AD patients exhibit reduced expression of PNNs, particularly in the hippocampus (Baig et al., 2005; Lendvai et al., 2013).”

What the sources say

• Not checked yetcites Baig et al., 2005 source
• Not checked yetcites Lendvai et al., 2013 source

In the paper

“The neuroprotective abilities of PNNs may stem from their ability to act as a barrier for oxidative stress-inducing molecules, such as metal ions.”

In the paper

“the CSPGs present in PNNs appear to inhibit axonal growth (Kwok et al., 2011).”

What the sources say

• Not checked yetcites Kwok et al., 2011 source

In the paper

“More cells died when pretreated with chABC (Miyata et al., 2007).”

What the sources say

• Not checked yetcites Miyata et al., 2007 source

In the paper

“cortical cells expressing PNNs exhibited accumulation of iron in post-fixed brain tissues obtained from both AD and normally aged controls (Reinart et al., 2003).”

What the sources say

• Not checked yetcites Reinart et al., 2003 source

In the paper

“but also contributed to expanded receptive fields of uninjured primary afferents (Bradbury et al., 2002; Massey et al., 2006).”

What the sources say

• Not checked yetcites Bradbury et al., 2002 source
• Not checked yetcites Massey et al., 2006 source

In the paper

“Recent work has reported changes in PNN integrity in epilepsy.”

In the paper

“this decrease in inhibitory cell function may underlie epilepsy-like activity following stroke (Hobohm et al., 2005; Xie et al., 2014).”

What the sources say

• Not checked yetcites Hobohm et al., 2005 source
• Not checked yetcites Xie et al., 2014 source

In the paper

“in cortical areas surrounding the infarct and outside of the glial scar, WFA-expressing PNNs are completely degraded by day 7”

What the sources say

• Not checked yetcites Hobohm et al., 2005 source

In the paper

“Neurons that exhibit buildup of tau protein and neurofibrillary tangles are more likely to lack PNNs (Brückner et al., 1999; Morawski et al., 2010).”

What the sources say

• Not checked yetcites Brückner et al., 1999 source
• Not checked yetcites Morawski et al., 2010 source

In the paper

“MMP-9 may be responsible for this ECM reorganization”

What the sources say

• Not checked yetcites Zhang et al., 2011 source
• Not checked yetcites Chaturvedi and Kaczmarek, 2014
• Not checked yetcites Liu et al., 2014 source

In the paper

“a number of studies have demonstrated increased MMP-9 levels following CNS injury and stroke in humans as well as animal models (Zhang et al., 2011; Chaturvedi and Kaczmarek, 2014; Liu et al., 2014).”

What the sources say

• Not checked yetcites Zhang et al., 2011 source
• Not checked yetcites Chaturvedi and Kaczmarek, 2014
• Not checked yetcites Liu et al., 2014 source

In the paper

“Accumulation of lipofuscin, a byproduct of iron-catalyzed oxidative stress, was also observed in cells without PNN (Morawski et al., 2004).”

What the sources say

• Not checked yetcites Morawski et al., 2004 source

In the paper

“RT-PCR analysis of the affected tissue indicated upregulation of neurocan, which peaked on the third day following middle cerebral artery occlusion”

What the sources say

• Not checked yetcites Carmichael et al., 2005 source

In the paper

“focal cortical stroke in rats contributes to upregulation of a number of CSPG-encoding genes particularly near the infarct and glial scar.”

What the sources say

• Not checked yetcites Carmichael et al., 2005 source

In the paper

“CSPG degradation via application of chABC promoted regeneration of dorsal column axons after injury.”

What the sources say

• Not checked yetcites Bradbury et al., 2002 source
• Not checked yetcites Massey et al., 2006 source

In the paper

“When sensory axons were transplanted into adult rats with dorsal column lesions, neurons were able to sprout and extend their processes to additional denervated areas, but failed to penetrate the original lesion sites”

What the sources say

• Not checked yetcites Davies et al., 1999 source
• Not checked yetcites Kaas et al., 2008 source

In the paper

“In rat spinal cord injury models, increased concentrations of CSPGs and PNN expression were found at injury sites and surrounding secondary dorsal column relay neurons (Massey et al., 2008).”

What the sources say

• Not checked yetcites Massey et al., 2008 source

In the paper

“Similar degradation of WFA-expressing PNNs in the neocortex has also been observed following thromboembolic middle cerebral artery occlusion in rats, permanent middle artery occlusion in mice, and focal cerebral ischemia in sheep (Härtig et al., 2017).”

What the sources say

• Not checked yetcites Härtig et al., 2017 source

In the paper

“as well as versican and brevican, both of which peaked by day 28 (Carmichael et al., 2005).”

What the sources say

• Not checked yetcites Carmichael et al., 2005 source