GLOBAL-ISCHEMIA - HIPPOCAMPAL PATHOLOGY AND SPATIAL DEFICITS IN THE WATER MAZE

Spatial deficits were assessed in male Wistar rats which had undergone 4 vessel occlusion for 5, 10, 15 or 30 min. Relationships between the extent of brain damage, the duration of 4-vessel occlusion, and the b ehavioural impairment consequent upon ischaemia were investigated. Sta rting 13-18 days after occlusion, rats were trained to find a hidden p latform in a iMorris water maze. All ischaemic groups were impaired on some performance indices relative to controls, in both acquisition an d retention of the platform location. Increasing the duration of ischa emia increased behavioural deficits on some measures, but there was no clear-cut evidence that longer durations of ischaemia resulted in inc reased behavioural impairments. Histological assessment, at two corona l levels in hippocampus and four coronal levels in cortex and striatum , revealed CA1 cell loss in all ischaemic groups, which varied between 10-100% across the range of durations employed. CA1 cell loss increas ed as both a linear and quadratic function of increasing the duration of ischaemia. In rats subjected to 5-15 min ischaemia, cell loss was a lmost exclusively confined to the CA1 area. In rats subjected to 30 mi n ischaemia there was additional, variable damage in hippocampal areas CA2, 3 and 4, substantial cell loss in the striatum (50-70%) and some neuronal damage in the cortex (largely in layer III). However correla tions between CA1 cell loss in ischaemic rats and indices of spatial a bility were non-significant, despite avoiding bias in the analysis by ensuring that only those rats with submaximal CA1 cell loss estimates and behavioural impairments were included. Given the lack of correlati on between damage to the CA1 region and behaviour, it is suggested tha t CA1 cell loss may not be the only determinant of the water maze defi cits displayed by 4-vessel occlusion ischaemic rats.