Global ischaemia: hippocampal pathology and spatial deficits in the water maze

Abstract

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 behavioural impairment consequent upon ischaemia were investigated. Starting 13-18 days after occlusion, rats were trained to find a hidden platform in a Morris water maze. All ischaemic groups were impaired on some performance indices relative to controls, in both acquisition and retention of the platform location. Increasing the duration of ischaemia increased behavioural deficits on some measures, but there was no clear-cut evidence that longer durations of ischaemia resulted in increased behavioural impairments. Histological assessment, at two coronal 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 increased as both a linear and quadratic function of increasing the duration of ischaemia. In rats subjected to 5-15 min ischaemia, cell loss was almost exclusively confined to the CA1 area. In rats subjected to 30 min 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 correlations between CA1 cell loss in ischaemic rats and indices of spatial ability 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 correlation between damage to the CA1 region and behaviour, it is suggested that CA1 cell loss may not be the only determinant of the water maze deficits displayed by 4-vessel occlusion ischaemic rats.