PMID- 19187292
OWN - NLM
STAT- MEDLINE
DCOM- 20090305
LR  - 20220309
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 50 Suppl 2
IP  - Suppl 2
DP  - 2009 Feb
TI  - Epilepsy following cortical injury: cellular and molecular mechanisms as targets 
      for potential prophylaxis.
PG  - 30-40
LID - 10.1111/j.1528-1167.2008.02008.x [doi]
AB  - The sequelae of traumatic brain injury, including posttraumatic epilepsy, 
      represent a major societal problem. Significant resources are required to develop 
      a better understanding of the underlying pathophysiologic mechanisms as targets 
      for potential prophylactic therapies. Posttraumatic epilepsy undoubtedly involves 
      numerous pathogenic factors that develop more or less in parallel. We have 
      highlighted two potential "prime movers": disinhibition and development of new 
      functional excitatory connectivity, which occur in a number of animal models and 
      some forms of epilepsy in humans. Previous experiments have shown that 
      tetrodotoxin (TTX) applied to injured cortex during a critical period early after 
      lesion placement can prevent epileptogenesis in the partial cortical ("undercut") 
      model of posttraumatic epilepsy. Here we show that such treatment markedly 
      attenuates histologic indices of axonal and terminal sprouting and presumably 
      associated aberrant excitatory connectivity. A second finding in the undercut 
      model is a decrease in spontaneous inhibitory events. Current experiments show 
      that this is accompanied by regressive alterations in fast-spiking 
      gamma-aminobutyric acid (GABA)ergic interneurons, including shrinkage of 
      dendrites, marked decreases in axonal length, structural changes in inhibitory 
      boutons, and loss of inhibitory synapses on pyramidal cells. Other data support 
      the hypothesis that these anatomic abnormalities may result from loss of trophic 
      support normally provided to interneurons by brain-derived neurotrophic factor 
      (BDNF). Approaches that prevent these two pathophysiologic mechanisms may offer 
      avenues for prophylaxis for posttraumatic epilepsy. However, major issues such as 
      the role of these processes in functional recovery from injury and the timing of 
      the critical period(s) for application of potential therapies in humans need to 
      be resolved.
FAU - Prince, David A
AU  - Prince DA
AD  - Department of Neurology and Neurological Sciences, Stanford University School of 
      Medicine, Stanford, California 94305, USA. daprince@stanford.edu
FAU - Parada, Isabel
AU  - Parada I
FAU - Scalise, Karina
AU  - Scalise K
FAU - Graber, Kevin
AU  - Graber K
FAU - Jin, Xiaoming
AU  - Jin X
FAU - Shen, Fran
AU  - Shen F
LA  - eng
GR  - NS12151/NS/NINDS NIH HHS/United States
GR  - T32 HD007430/HD/NICHD NIH HHS/United States
GR  - R01 NS039579/NS/NINDS NIH HHS/United States
GR  - R01 NS039579-08/NS/NINDS NIH HHS/United States
GR  - NS02167/NS/NINDS NIH HHS/United States
GR  - P50 NS012151/NS/NINDS NIH HHS/United States
GR  - R56 NS039579/NS/NINDS NIH HHS/United States
GR  - P01 NS012151-330020/NS/NINDS NIH HHS/United States
GR  - P01 NS012151/NS/NINDS NIH HHS/United States
GR  - K99 NS057940-02/NS/NINDS NIH HHS/United States
GR  - K99 NS057940/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 4368-28-9 (Tetrodotoxin)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/pharmacology
MH  - Brain Injuries/*complications/pathology/physiopathology
MH  - Cerebral Cortex/*injuries/pathology/physiopathology
MH  - Disease Models, Animal
MH  - Epilepsy, Post-Traumatic/pathology/*physiopathology/prevention & control
MH  - Humans
MH  - Interneurons/drug effects/pathology/physiology
MH  - Nerve Net/drug effects/pathology/physiopathology
MH  - Nerve Regeneration/drug effects/physiology
MH  - Neural Inhibition/drug effects/physiology
MH  - Neuronal Plasticity/drug effects/physiology
MH  - Pyramidal Cells/drug effects/pathology/physiology
MH  - Tetrodotoxin/pharmacology
MH  - gamma-Aminobutyric Acid/metabolism
PMC - PMC2710960
MID - NIHMS97640
COIS- Disclosure: The authors declare no conflicts of interest.
EDAT- 2009/02/24 09:00
MHDA- 2009/03/06 09:00
PMCR- 2010/02/01
CRDT- 2009/02/04 09:00
PHST- 2009/02/04 09:00 [entrez]
PHST- 2009/02/24 09:00 [pubmed]
PHST- 2009/03/06 09:00 [medline]
PHST- 2010/02/01 00:00 [pmc-release]
AID - EPI2008 [pii]
AID - 10.1111/j.1528-1167.2008.02008.x [doi]
PST - ppublish
SO  - Epilepsia. 2009 Feb;50 Suppl 2(Suppl 2):30-40. doi: 
      10.1111/j.1528-1167.2008.02008.x.