REDUCED CYTOCHROME-OXIDASE AND MEMORY DYSFUNCTION AFTER CHRONIC BRAINISCHEMIA IN AGED RATS

The effects of chronic cerebrovascular ischemia on memory function and cytochrome oxidase (GO) activity were investigated. Cerebrovascular i nsufficiency was induced by permanent bilateral carotid artery ligatio n (2-VO) in 19 month old rats. Sham surgery in no-vessel occlusion (no -VO) rats were used for controls. Memory function was tested 1 week pr ior to surgery and then weekly for 21 days using the Morris water maze . Regional brain activity of CO was measured 4 weeks after surgery by quantitative histochemistry. Histologic examination of brain slices wa s used to evaluate any neuropathology present. Results showed that 2-V O rats were significantly impaired in the water maze task at each test ing period with respect to no-VO controls. In addition, CO activity in 2-VO rats was markedly reduced only in the dorsal CA1 region of the h ippocampus and in the posterior parietal cortex. These brain regions a re involved in visuo-spatial memory mechanisms. Analysis of other brai n regions in 2-VO rats did not reveal further CO activity changes. The re were no damaged or loss of neurons in 2-VO or no-VO groups in any r egion examined, including CA1 and posterior parietal cortex. The CA1 r egion however, is known to undergo neuronal loss 25 weeks after chroni c 2-VO suggesting that this vascular insult can induce a slowly-evolvi ng cascade consisting of neuronal damage, atrophy and death. The prese nt findings indicate that reduced CO activity in CA1 and posterior par ietal regions can predict neural damage and atrophy prior to structura l perikaryal pathology following chronic brain ischemia. In addition, the data shows that neuronal energy metabolic deficiency may initiate visuo-spatial memory impairment in this aging rat model. (C) 1997 Else vier Science Ireland Ltd.