Basic fibroblast growth factor is highly neuroprotective against seizure-induced long-term behavioural deficits.
Basic fibroblast growth factor has been reported to protect neurons of various structures from excitotoxic damage. To study the effects of basic fibroblast growth factor on seizure-induced brain damage we infused the growth factor into the lateral ventricles of 35-day-old rats receiving convulsant dosages of kainic acid. Artificial cerebrospinal fluid or basic fibroblast growth factor at dosages of 0.5 ng/h or 2.5 ng/h was infused into the lateral ventricle continuously for seven days starting two days before and continuing for five days after the animals had kainic acid-induced status epilepticus. At age 80 days the animals underwent behavioural testing using the water maze, open field, and handling tests and at age 95 days were tested for seizure threshold using flurothyl inhalation. Neither artificial cerebrospinal fluid or basic fibroblast growth factor modified the latency or duration of the acute seizures following kainic acid. However, rats infused with 2.5 ng/h, but not 0.5 ng/h of basic fibroblast growth factor, had fewer spontaneous recurrent seizures, a higher seizure threshold, better performance in the handling, open field and water maze test, and less cell loss in the hippocampus when compared to rats receiving artificial cerebrospinal fluid or 0.5 ng/h of basic fibroblast growth factor. These results show that basic fibroblast growth factor has a dose-related neuroprotective effect against seizure-induced long-term behavioural deficits when administered by osmotic pump prior to seizure onset. This neuroprotective effect is not related to an anticonvulsant effect.
Liu
Z
Z
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts, USA.
Holmes
G L
GL
D000375:Aging / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D003072:Cognition Disorders / Q000517:prevention & control / Q000523:psychology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005481:Flurothyl; D006234:Handling, Psychological; D007608:Kainic Acid / Q000633:toxicity; D007859:Learning Disabilities / Q000517:prevention & control / Q000523:psychology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012640:Seizures / Q000139:chemically induced / Q000523:psychology*; D013226:Status Epilepticus / Q000517:prevention & control / Q000523:psychology
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; D005481:Flurothyl; D007608:Kainic Acid