Summary:The behavioral and neurochemical changes in the chronic phase of permanent occlusion of the right middle cerebral artery (MCA) in rats were investigated. One month after MCA occlusion, 23 rats were unable to solve a radial eight-arm maze task during an entire I-month period, whereas seven rats were able to solve this task. Three months after occlusion, 19 MCA-oc cluded rats failed to solve the task successfully again for at least I month (the cognitively impaired rats), whereas II MCA-occluded rats were able to solve it (the cogni tively unimpaired rats). The rats that underwent behav ioral testing were examined for any changes in the ace tylcholine (ACh) levels in the hippocampus using HPLC with electrochemical detection or the formation of long term potentiation (L TP) in the population spike of the hippocampal CAl field. The immunohistochemical distriPermanent unilateral middle cerebral artery (MCA) occlusion in rats is widely used as a model of focal cerebral ischemia. In the acute phase, this model selectively causes infarction in the ipsilateral cerebral cortex and caudate nucleus-putamen com plex (Tamura et aI., 1981 a; lizuka et aI., 1989). Af ter the infarction in the territory of the MCA, �2 weeks after MCA occlusion, progressive shrinkage occurs in the ipsilateral thalamus (Fujie et aI., 1990) Received March 31, 1994; final revision received October 14, 1995; accepted February 27, 1995. Address correspondence and reprint requests to Dr. Michihiro Fujiwara, Department of Physiology and Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-01, Japan.Abbreviations used: MeA, middle cerebral artery; LTP, long term potentiation; MAP2, microtubule-associated protein 2; GFAP, glial fibrillary acidic protein.
1012bution of either the microtubule-associated protein 2 (MAP2) or glial fibrillary acidic protein (GF AP) in the hippocampus of the cognitively impaired rats was also studied. In the cognitively impaired rats, neither the sup pression of the induction of L TP, nor the degradation of MAP2, nor the increase in the GFAP immunoreactivity was observed in the hippocampus. The levels of ACh in the hippocampus did not change significantly among the cognitively impaired, unimpaired, and the sham-operated rats. These results suggest that MCA occlusion is capable of producing long-term spatial cognitive disturbance in rats without any evidence of neurobiological damage in the hippocampus. Key Words: Focal cerebral ischemia Memory-Long-term potentiation-Microtubule-asso ciated protein 2-Glial fibrillary acidic protein.