CHRONIC CEREBRAL HYPOPERFUSION - PATHOLOGICAL AND BEHAVIORAL CONSEQUENCES

OBJECTIVE: Although the effects of acute ischemic insults to the brain are well known, the effects related to chronic ischemia are poorly de lineated. The pathological and behavioral changes induced by a chronic noninfarctional reduction in cerebral blood flow of 25 to 50% maintai ned for 6 months were assessed. METHODS: In each of 18 male Sprague-Da wley rats, an arteriovenous fistula was created in the neck via an ana stomosis between the right external jugular vein and the right common carotid artery to induce cerebral hypoperfusion. Nineteen age-matched animals comprised a control group. Six months after surgery, the anima ls were examined using light and electron microscopic techniques, as w ell as via a battery of behavioral tests (motor, open field, and T-maz e). RESULTS: Examination of the hippocampus by using light microscopy revealed disorganization of the CA1 sector with an increased number of astrocytes. Transmission electron microscopy of the CA1 region demons trated neurons with increased lipofuscin pigment and central nucleoli and astrocytes with more numerous cytosolic mitochondria. Motor perfor mance testing revealed no gross motor deficits, although open-field as sessment demonstrated increased exploratory behavior in rats with fist ulas. Finally, T-maze testing results suggested that errors in working memory were more common in rats undergoing chronic cerebral hypoperfu sion (P < 0.05). CONCLUSIONS: These findings suggest that chronic redu ctions in cerebral blood flow of a magnitude previously thought to be harmless to neurons (i.e., reduced by 25-50%) do alter neuronal struct ure and affect whole animal behavior. Such a scenario may be responsib le for a symptomatology secondary to arteriovenous steal and severe ca rotid stenoses. The mechanisms are still unknown.