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 delineated. The pathological and behavioral changes induced by a chronic noninfarctional reduction in cerebral blood flow of 25 to 50% maintained for 6 months were assessed.


METHODS
In each of 18 male Sprague-Dawley rats, an arteriovenous fistula was created in the neck via an anastomosis 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 animals were examined using light and electron microscopic techniques, as well as via a battery of behavioral tests (motor, open field, and T-maze).


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 demonstrated neurons with increased lipofuscin pigment and central nucleoli and astrocytes with more numerous cytosolic mitochondria. Motor performance testing revealed no gross motor deficits, although open-field assessment demonstrated increased exploratory behavior in rats with fistulas. Finally, T-maze testing results suggested that errors in working memory were more common in rats undergoing chronic cerebral hypoperfusion (P < 0.05).


CONCLUSIONS
These findings suggest that chronic reductions in cerebral blood flow of a magnitude previously thought to be harmless to neurons (i.e., reduced by 25-50%) do alter neuronal structure and affect whole animal behavior. Such a scenario may be responsible for a symptomatology secondary to arteriovenous steal and severe carotid stenoses. The mechanisms are still unknown.
Sekhon
L H
LH
Department of Surgery, University of Sydney, Australia.
Morgan
M K
MK
Spence
I
I
Weber
N C
NC
D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D002908:Chronic Disease; D005106:Exploratory Behavior / Q000502:physiology; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D011939:Mental Recall / Q000502:physiology; D008854:Microscopy, Electron; D009048:Motor Skills / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley