Cited by 211Epilepsy research and treatmentNeuroscience and Neuropharmacology ResearchPharmacological Effects and Toxicity Studies

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Transient Inhibition of TrkB Kinase after Status Epilepticus Prevents Development of Temporal Lobe Epilepsy

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Liu, Gumei, Gu, Bin, He, Xiao-Ping, Joshi, Rasesh B., Wackerle, Harold D., Rodriguiz, Ramona Marie, Wetsel, William C., McNamara, James O.·2013·Neuron

DOI 10.1016/j.neuron.2013.04.027PMC PMC3744583

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Abstract

Temporal lobe epilepsy is the most common and often devastating form of human epilepsy. The molecular mechanism underlying the development of temporal lobe epilepsy remains largely unknown. Emerging evidence suggests that activation of the BDNF receptor TrkB promotes epileptogenesis caused by status epilepticus. We investigated a mouse model in which a brief episode of status epilepticus results in chronic recurrent seizures, anxiety-like behavior, and destruction of hippocampal neurons. We used a chemical-genetic approach to selectively inhibit activation of TrkB. We demonstrate that inhibition of TrkB commencing after status epilepticus and continued for 2 weeks prevents recurrent seizures, ameliorates anxiety-like behavior, and limits loss of hippocampal neurons when tested weeks to months later. That transient inhibition commencing after status epilepticus can prevent these long-lasting devastating consequences establishes TrkB signaling as an attractive target for developing preventive treatments of epilepsy in humans.

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Authors: Liu, G., Gu, B., He, X.-P., Joshi, R. B., Wackerle, H. D., Rodriguiz, R. M., Wetsel, W. C., & McNamara, J. O.
Affiliations: Duke Medical Center (US)
Duke University (US)
Corresponding author: McNamara, James O.
ORCID: Gu, Bin
Joshi, Rasesh B.
Rodriguiz, Ramona Marie
Wetsel, William C.
McNamara, James O.
Venue: Neuron
Publisher: Elsevier BV
Published: 2013-07
Volume: 79
Issue: 1
Pages: 31-38
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2013.04.027
PMC: PMC3744583
OpenAlex: W2078385314
Cited by: 210
References: 36
Citations by year: 2026: 8 · 2025: 3 · 2024: 12 · 2023: 7 · 2022: 6 · 2021: 16 · 2020: 18 · 2019: 29 · 2018: 15 · 2017: 26 · 2016: 26 · 2015: 15 · 2014: 24 · 2013: 5
FWCI: 16.53
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
Funders: National Institutes of Health
National Institute of General Medical Sciences (T32GM008441)
National Institute of Neurological Disorders and Stroke (NS56217, R01NS060728, R01NS056217, NS060728)
Topics: Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Keywords: temporal lobe epilepsy, status epilepticus, BDNF receptor, epileptogenesis, hippocampal neuronal loss, anxiety-like behavior, recurrent seizures, epilepsy prevention, mouse model
MeSH terms: Amygdala, Animals, Behavior, Animal, Disease Models, Animal, Electroencephalography, Epilepsy, Temporal Lobe, Hippocampus, Kainic Acid, Motor Activity, Neurons, Status Epilepticus, Signal Transduction, Receptor, trkB, Mice

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Transient Inhibition of TrkB Kinase after Status Epilepticus Prevents Development of Temporal Lobe Epilepsy

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