title: Phenobarbital administration directed against kindled seizures delays functional recovery following brain insult.
abstract: Anti-convulsant drug administration or recurrent seizures can impact functional recovery following brain insult. The nature of that impact depends on a variety of factors, including timing of drug administration and drug mechanism of action, as well as seizure number, timing, and severity. The objective of this study was to determine the functional consequences of anti-convulsant administration directed against seizure activity in brain-damaged animals. To this end, phenobarbital was coupled with daily electrical kindling of the amygdala beginning 48 h after a unilateral anteromedial cortex lesion. Recovery from somatosensory deficits was assessed, as was regional atrophy and basic fibroblast growth factor (bFGF) expression. Animals receiving phenobarbital prior to daily kindling failed to recover within 2 months of testing. In contrast, animals receiving saline prior to kindling as well as phenobarbital-treated non-kindled animals recovered within 2 months after the lesion. Though the exact mechanisms underlying these behavioral phenomena remain uncertain, patterns of bFGF expression among the groups provide some insight. Taken together, results from the present study suggest that anti-convulsant drug administration directed against subclinical seizure activity can be more detrimental to functional recovery than seizures alone or anti-convulsant drug treatment after seizure activity has occurred.
authors.affiliation: Behavioral Neuroscience Program, Department of Psychology, Campus Box 345, The University of Colorado, Boulder, CO, USA.
authors.forename: S
authors.initials: S
authors.lastname: Montañez
authors.forename: A E
authors.initials: AE
authors.lastname: Kline
authors.forename: T A
authors.initials: TA
authors.lastname: Gasser
authors.forename: T D
authors.initials: TD
authors.lastname: Hernandez
mesh_terms: D000679:Amygdala / Q000503:physiopathology*; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001253:Astrocytes / Q000378:metabolism; D001925:Brain Damage, Chronic / Q000150:complications* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000293:injuries; D004334:Drug Administration Schedule; D004558:Electric Stimulation / Q000009:adverse effects; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D011292:Premedication; D011597:Psychomotor Performance; D051381:Rats; D011930:Reaction Time; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology
chemical_list: D000927:Anticonvulsants; D016222:Fibroblast Growth Factor 2; D010634:Phenobarbital