PMID- 24801281
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20211021
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 92
IP  - 10
DP  - 2014 Oct
TI  - Acute administration of the small-molecule p75(NTR) ligand does not prevent 
      hippocampal neuron loss or development of spontaneous seizures after 
      pilocarpine-induced status epilepticus.
PG  - 1307-18
LID - 10.1002/jnr.23402 [doi]
AB  - Neurotrophins, such as brain-derived neurotrophic factor (BDNF), are initially 
      expressed in a precursor form (e.g., pro-BDNF) and cleaved to form mature BDNF 
      (mBDNF). After pilocarpine-induced status epilepticus (SE), increases in 
      neurotrophins regulate a wide variety of cell-signaling pathways, including 
      prosurvival and cell-death machinery in a receptor-specific manner. Pro-BDNF 
      preferentially binds to the p75 neurotrophin receptor (p75(NTR) ), whereas mBDNF 
      is the major ligand of the tropomyosin-related kinase receptor. To elucidate a 
      potential role for p75(NTR) in acute stages of epileptogenesis, rats were 
      injected prior to and at onset of SE with LM11A-31, a small-molecule ligand that 
      binds to p75(NTR) to promote survival signaling and inhibit neuronal cell death. 
      Modulation of early p75(NTR) signaling and its effects on electrographic SE, 
      SE-induced neurodegeneration, and subsequent spontaneous seizures were examined 
      after LM11A-31 administration. Despite an established neuroprotective effect of 
      LM11A-31 in several animal models of neurodegenerative disorders (e.g., 
      Alzheimer's disease, traumatic brain injury, and spinal cord injury), high-dose 
      LM11A-31 administration prior to and at onset of SE did not reduce the intensity 
      of electrographic SE, prevent SE-induced neuronal cell injury, or inhibit the 
      progression of epileptogenesis. Further studies are required to understand the 
      role of p75(NTR) activation during epileptogenesis and in seizure-induced cell 
      injury in the hippocampus, among other potential cellular pathologies 
      contributing to the onset of spontaneous seizures. Additional studies utilizing 
      more prolonged treatment with LM11A-31 are required to reach a definite 
      conclusion on its potential neuroprotective role in epilepsy.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Grabenstatter, H L
AU  - Grabenstatter HL
AD  - Department of Pediatrics, Division of Neurology, and Translational Epilepsy 
      Research Program, University of Colorado School of Medicine, Aurora, Colorado.
FAU - Carlsen, J
AU  - Carlsen J
FAU - Raol, Y H
AU  - Raol YH
FAU - Yang, T
AU  - Yang T
FAU - Hund, D
AU  - Hund D
FAU - Cruz Del Angel, Y
AU  - Cruz Del Angel Y
FAU - White, A M
AU  - White AM
FAU - Gonzalez, M I
AU  - Gonzalez MI
FAU - Longo, F M
AU  - Longo FM
FAU - Russek, S J
AU  - Russek SJ
FAU - Brooks-Kayal, A R
AU  - Brooks-Kayal AR
LA  - eng
GR  - R01 NS051710/NS/NINDS NIH HHS/United States
GR  - UL1 TR001082/TR/NCATS NIH HHS/United States
GR  - R01NS051710/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140507
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Anticonvulsants)
RN  - 0 (Fluoresceins)
RN  - 0 (LM11A-31)
RN  - 0 (Morpholines)
RN  - 0 (Muscarinic Agonists)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (fluoro jade)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - 04Y7590D77 (Isoleucine)
RN  - 136958-07-1 (Ngfr protein, rat)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Anticonvulsants/blood/*therapeutic use
MH  - Brain Waves/drug effects
MH  - Disease Models, Animal
MH  - Electroencephalography
MH  - Fluoresceins
MH  - Isoleucine/*analogs & derivatives/blood/therapeutic use
MH  - Morpholines/blood/*therapeutic use
MH  - Muscarinic Agonists/toxicity
MH  - Nerve Tissue Proteins
MH  - Pilocarpine/toxicity
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Growth Factor
MH  - Receptors, Nerve Growth Factor/chemistry/*metabolism
MH  - Spectrum Analysis
MH  - Status Epilepticus/chemically induced/*drug therapy
MH  - Time Factors
PMC - PMC4134742
MID - NIHMS590179
OTO - NOTNLM
OT  - LM11A-31 p75NTR
OT  - neurotrophin
OT  - pilocarpine
OT  - seizure
OT  - status epilepticus
EDAT- 2014/05/08 06:00
MHDA- 2015/05/12 06:00
PMCR- 2015/10/01
CRDT- 2014/05/08 06:00
PHST- 2013/12/27 00:00 [received]
PHST- 2014/03/24 00:00 [revised]
PHST- 2014/03/31 00:00 [accepted]
PHST- 2014/05/08 06:00 [entrez]
PHST- 2014/05/08 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
PHST- 2015/10/01 00:00 [pmc-release]
AID - 10.1002/jnr.23402 [doi]
PST - ppublish
SO  - J Neurosci Res. 2014 Oct;92(10):1307-18. doi: 10.1002/jnr.23402. Epub 2014 May 7.