HIPPOCAMPAL KINDLING PROTECTS SEVERAL STRUCTURES FROM THE NEURONAL DAMAGE RESULTING FROM KAINIC ACID-INDUCED STATUS EPILEPTICUS

In an attempt to study the effects of piriform cortex damage on kindle d seizure propagation, we administered kainic acid (12 mg/kg; i.p.) to rats previously kindled from the dorsal hippocampus. Unexpectedly, th e ensuing status epilepticus (SE) in the kindled rats did not result i n the piriform cortex damage normally observed in naive rats. As a res ult of this surprising finding, a more comprehensive investigation was undertaken to compare dorsal hippocampal kindled and control rats on their electrographic and behavioral SE development and subsequent brai n damage. The SE induction profile and the pattern of brain damage obs erved in our control rats was similar to previous reports [Neuroscienc e, 14 (1985) 375-403; Brain Res., 218 (1981) 299-318]. By contrast, al though fewer kindled rats than controls responded to the initial dose of kainic acid with electrographic and behavioral seizures, those many kindled rats that did respond, showed a pattern of SE induction that was different from controls. Kindled rats manifested fewer 'wet dog sh akes', more generalized convulsions and a faster development of severe limbic status (SLS) than controls. In addition, without pharmacologic al intervention, the SLS continued longer in kindled rats than in cont rols. Histological examination revealed brain damage in kindled rats t hat was markedly different from controls. Unlike controls, kindled rat s had no damage in the piriform cortex or substantia nigra reticulata and minimal hippocampal damage, yet showed midline thalamic and anteri or olfactory nuclei damage similar to controls. These differences were observed from 1 to 28 days after kindling. Although the mechanism(s) of this kindling-based neuroprotection is not known, its discovery sho uld add importantly to our understanding of epilepsy-induced alteratio ns of subsequent neuronal function.