Abstracts

The goal of this study was to modify the pilocarpine model to allow an examination of the effects of extrahippocampal but not hippocampal degeneration. To this end, pilocarpine-induced status epilepticus was induced, and then status was abbreviated by anesthesia. We hypothesized that anesthesia would reduce the typical pattern of hippocampal degeneration that follows pilocarpine-induced status epilepticus, but not necessarily block damage in other vulnerable areas of the brain. Adult male Sprague-Dawley rats ([sim]200g) were pretreated with atropine methylbromide (1mg/kg i.p.) and 30[apos] later with pilocarpine hydrochloride (380mg/kg i.p.). Status epilepticus was truncated at different times and with different anesthetics (pentobarbital, phenobarbital, ketamine) systematically. Animals were sacrificed 1 day, 3 days, 1 wk, or 1 month after status. Fluorojade, silver degeneration, or immunocytochemistry (NeuN, neuropeptide Y) was conducted on 50 [mu]m sections after 4% paraformaldehyde transcardial perfusion. Only pentobarbital protected the hippocampus consistently (n=11/13 rats; 20mg/kg i.p. within 10[apos] of the onset of status and 10mg/kg i.p. 50[apos] later), and only if anesthesia began [lt]70[apos] after status onset (or, if anesthesia began between 70[apos] and 120[apos], head bobbing stopped by 20[apos]). Animals not reaching these critieria had hippocampal damage (n=11/11). Protected hippocampi showed no fluorojade or silver degeneration of principal cells. But extrahippocampal damage occurred, and had a specific pattern, including entorhinal cortex (mostly medial layers III [amp] V/VI), lateral amygdala, perirhinal cortex (mostly deep horizontal cells), anterior dorsal midline thalamus, piriform and endopiriform nuclei (mostly deep layers), and basal hypothalamus. A few subicular pyramidal cells were degenerated in dorsal sections of 5/11 rats with protected hippocampi. In the 2 exceptional rats (anesthetized as above, but hippocampal damage occurred), hippocampal damage was restricted to dorsal CA1and subicular neurons. At 1 month, animals that reached criteria for anesthesia demonstrated degeneration in the same areas as animals killed at 1 or 3 days, but there was more terminal degeneration within these regions; hippocampal pyramidal cells remained protected. The hippocampus can be preserved after systemic pilocarpine if status is limited, yet specific extrahippocampal sites sustain damage even after these minimal periods of status. Results at 1 month indicate a possible progression of damage within extrahippocampal areas, but the results may also be explained by protracted neuronal death. Regardless, the hippocampus remained protected at 1 month, suggesting that this method can be used to produce an animal model of extrahippocampal damage. (Supported by NS 16109.)