Abstract

Previous studies have shown that the GABA-A receptor subunit composition changes with development and with certain seizure states such as status epilepticus (SE). The current proposal tests the hypothesis that the slowly developing temporal lobe epilepsy (TLE) often seen after SE is due to changes in the subunit composition. To test this hypothesis, the PI uses the pilocarpine-induced SE model in developing rats. Outcome measures of the GABA-A receptor are patch-clamping for conductance and pharmacological response changes and single-cell RNA analysis of the recorded cell. Similar studies will also be done in epileptic and non-epileptic pediatric populations. Finally, the effect of GABA active drugs on GABA receptor development will be examined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS038595-05
Application #
6639567
Study Section
Special Emphasis Panel (ZRG1-BDCN-5 (01))
Program Officer
Fureman, Brandy E
Project Start
1999-04-01
Project End
2004-11-30
Budget Start
2003-04-01
Budget End
2004-11-30
Support Year
5
Fiscal Year
2003
Total Cost
$369,494
Indirect Cost

  Institution

Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Simonato, Michele; Brooks-Kayal, Amy R; Engel Jr, Jerome et al. (2014) The challenge and promise of anti-epileptic therapy development in animal models. Lancet Neurol 13:949-60
Scharfman, Helen E; Brooks-Kayal, Amy R (2014) Is plasticity of GABAergic mechanisms relevant to epileptogenesis? Adv Exp Med Biol 813:133-50
Pitkänen, Asla; Nehlig, Astrid; Brooks-Kayal, Amy R et al. (2013) Issues related to development of antiepileptogenic therapies. Epilepsia 54 Suppl 4:35-43
Brooks-Kayal, Amy R; Bath, Kevin G; Berg, Anne T et al. (2013) Issues related to symptomatic and disease-modifying treatments affecting cognitive and neuropsychiatric comorbidities of epilepsy. Epilepsia 54 Suppl 4:44-60
Chapman, Kevin E; Raol, Yogendra H; Brooks-Kayal, Amy (2012) Neonatal seizures: controversies and challenges in translating new therapies from the lab to the isolette. Eur J Neurosci 35:1857-65
Baram, Tallie Z; Jensen, Frances E; Brooks-Kayal, Amy (2011) Does acquired epileptogenesis in the immature brain require neuronal death. Epilepsy Curr 11:21-6
Gonzalez, Marco I; Brooks-Kayal, Amy (2011) Altered GABA(A) receptor expression during epileptogenesis. Neurosci Lett 497:218-22
Brooks-Kayal, Amy (2011) Molecular mechanisms of cognitive and behavioral comorbidities of epilepsy in children. Epilepsia 52 Suppl 1:13-20
Frye, Cheryl A; Rhodes, Madeline E; Raol, YogendraSinh H et al. (2006) Early postnatal stimulation alters pregnane neurosteroids in the hippocampus. Psychopharmacology (Berl) 186:343-50
Raol, Yogendrasinh H; Zhang, Guojun; Lund, Ingrid V et al. (2006) Increased GABA(A)-receptor alpha1-subunit expression in hippocampal dentate gyrus after early-life status epilepticus. Epilepsia 47:1665-73

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