Memory Impairment Following Transient Global Cerebral Ischemia in Rats: Relationship to Neuropathology in the Hippocampus and Perirhinal Cortex

Memory Impairment Following Transient Global Cerebral Ischemia in Rats: Relationship to Neuropathology in the Hippocampus and Perirhinal Cortex Pavel Piterkin Memory impairments following global cerebral ischemia have traditionally been associated with damage to the hippocampus (HPC), but some ensuing impairments, such as object-recognition deficits, suggest the presence of extra-hippocampal neuropathology. In the present study, object-recognition memory, object-discrimination learning, and allocentric-spatial working-memory in rats were assessed following global cerebral ischemia (15 min; 4VO), or sham-ischemia. Ischemic rats were impaired on a delayedmatching-to-place (DMTP) water-maze task, and performed normally on a novel-objectpreference (NOP) test of object-recognition memory after a 15-min retention interval, but displayed deficits after a 24-hr interval. Ischemic rats learned object-discrimination problems at normal rates, and displayed normal 24-hr retention of the discriminations, suggesting that their object-memory impairment may have been specific to recognition. Upon completion of behavioral testing, the HPC and perirhinal cortex (PRh) were examined by visual quantification of Nissl-stained neurons, as well as immunohistochemical staining for glial-fibrillary acidic protein (GFAP). Ischemic rats displayed significant cell-loss and increased GFAP expression in both, the HPC and PRh. DMTP deficits were significantly correlated with the degree of cell loss and GFAP expression in the HPC. In addition, the degree of PRh cell loss significantly correlated with the degree of NOP deficits. These findings suggest that PRh damage may make a significant contribution to ischemia-induced impairment of object-recognition memory.