Abstracts

We have previously reported on a seizure-like syndrome (NIS-L) in adult rats treated with low doses of kainate agonists during postnatal development. NIS-L is characterized by reproducible behavioural sequelae reminiscent of a stage 2 seizure, that manifests on exposure to a novel environment, such as the Morris Water Maze (MWM). Analysis of hippocampal cytoarchitecture in 17 month old rats expressing NIS-L has revealed hippocampal changes that resemble those observed in conventional animal models of temporal lobe epilepsy (TLE), including mossy fiber sprouting (abnormal growth of dentate granule cell axons) in the inner molecular layer (IML) of the dentate gyrus and in the stratum oriens of area CA3. The purpose of the current study was to explore this abnormal axonal growth in younger animals and in greater detail. SD rats were injected daily with either saline (n=23) or subconvulsive doses of the kainate agonist domoic acid (n=25) from post-natal day 8-14. When the animals reached adulthood two-thirds of each treatment group where exposed to the MWM and the incidence of the NIS-L syndrome was recorded. Hippocampal anatomy was then analyzed using Timm[apos]s stain for mossy fiber sprouting (15 sections per animal). Sprouting was assessed using density analysis software in conjunction with a standard qualitative scale. Mossy fiber sprouting (MFS) was assessed in the IML of the dentate gyrus, as well as in the stratum oriens and stratum lucidum of area CA3. Separate analyses were conducted for the dorsal, mid and ventral portions of the hippocampus. Results indicated that drug treated animals displayed increased IML MFS in the mid (F= 9.457; p= .004) and ventral (F= 8.063; p= .007) but not the dorsal (F= 1.632; p= .208) portions of the hippocampus. A significant increase in Timm[apos]s staining in treated animals was also detected in the stratum lucidum of area CA3 in the middle portion of the hippocampus (F= 7.715; p-.008). No significant increase in Timm[apos]s staining was detected in the stratum oriens of area CA3. These results confirm previous findings that perinatal injections of very low doses of kainate agonists produces increases in MFS in the IML of the dentate gyrus. Treated animals also display increased Timm[apos]s staining in the stratum lucidum of area CA3. However, unlike previous results in aged animals, no increase in MFS in the stratum oriens of area CA3 was detected in young adult animals. We conclude that treated animals display patterns of seizure-like behaviour and MFS that closely mimic those seen in clinical cases of TLE. (Supported by Natural Sciences and Egineering Research Council of Canada Atlantic Innovation Fund (ACCBR) Prince Edward Island Health Research Program, UPEI.)