Abstracts

Rational We are interested in identifying mechanisms by which repeated exposure to brief seizures can protect neurons from apoptotic and excitotoxic damage. Growth factors such as basic fibroblast growth factor (bFGF) have been shown to protect neurons against excitotoxic damage, and previous evidence indicates that mRNA for these factors is transiently increased by brief non-injurious seizures. To determine whether this change in mRNA impacts on bFGF protein levels, we have examined the levels of bFGF protein in several forebrain regions at various time points following acute or chronic exposure to electroshock seizures (ECS). Methods ECS treatment consisted of either 1 day (acute) or 7 days (chronic) of daily brief limbic seizures induced via corneal electrodes using a Wahlquist apparatus (200 msec, 30 mA). Controls were handled in the same way without passing current. Protein expression was measured with Western blotting from purified tissue extracts from olfactory bulb, hippocampus, frontal cortex and enthorinal cortex taken at 8, 20, 48, and 72 hrs after the last seizure. Results In the chronic ECS treated groups, elevation of bFGF protein was most pronounced in the frontal and entorhinal cortex; these increases were significant as compared with control animals and animals exposed to acute ECS. These increases were maximal at 20 hrs, and remained significantly elevated for as long as 72 hrs. Smaller increases were seen in the hippocampus, and no increases were detected in the olfactory bulb. Discussion The increases in bFGF immunoreactivity after chronic ECS are positively correlated with increases in mRNA across the various brain regions. The increases in bFGF protein follow the increase in mRNA by 12 hr and outlast it by more than 48 hr. Furthermore, chronic ECS, which has been shown to be neuroprotective against damage from status epilepticus, induced significantly more bFGF immunoreactivity than did acute ECS, which is not neuroprotective. These results support the possibility that an induction of bFGF may contribute to the neuroprotective effect of repeated brief seizure exposure.