Proepileptic influence of a focal vascular lesion affecting entorhinal cortex-CA3 connections after status epilepticus.

In limbic seizures, neuronal excitation is conveyed from the entorhinalcortex directly to CA1 and subicular regions. This phenomenonis associated with a reduced ability of CA3 to respond toentorhinal cortex inputs. Here, we describe a lesion that destroys theperforant path in CA3 after status epilepticus (SE) induced bypilocarpine injection in 8-week-old rats. Using magnetic resonanceimaging, immunohistochemical, and ultrastructural analyses, wedetermined that this lesion develops after 30 minutes of SE and ischaracterized by microhemorrhages and ischemia. After a longerperiod of SE, the lesion invariably involves the upper blade ofthe dentate gyrus. Adult rats treated with subcutaneous diazepam(20 mg kgj1 for 3 days) did not develop the dentate gyrus lesionand had less frequent spontaneous recurrent seizures (p G 0.01).Young (3-week-old) rats rarely (20%) developed the CA3 lesion,and their spontaneous seizures were delayed (p G 0.01). To investigatethe role of the damaged CA3 in seizure activity, wereinduced SE in adult and young epileptic rats. Using FosB/$FosBmarkers, we found induction of FosB/$FosB immunopositivity inCA3 neurons of young but not in adult rats. These experimentsindicate that SE can produce a focal lesion in the perforant path thatmay affect the roles of the hippocampus in epileptic rats.