Long-term cognitive dysfunction following experimental subarachnoid hemorrhage: new perspectives.
Cognitive dysfunction is increasingly recognized as a significant long-term complication following subarachnoid hemorrhage (SAH), affecting up to 60% of survivors. We proposed to determine the incidence and explore potential mechanisms of cognitive dysfunction in a rat model. The effects of intracisternal blood, saline and sham injections were compared. At five weeks, Morris water maze escape latency (P=0.001) and swimming distance (P=0.001) were significantly different between groups, with increased latencies and distances recorded in the blood group in spite of increased swimming speed. The number of morphologically intact cortical (r=-0.75, P=0.0001) and hippocampal CA1 (r=-0.80, P<0.0001) neurons correlated with escape latency. In spite of only slight early reductions in proximal cerebral arterial diameters, pronounced and prolonged reductions in regional cerebral blood flow were observed in SAH rats, suggesting microvascular dysfunction. In concordance, cerebral microangiographic perfusion remained incomplete even after 2 weeks. 8-hydroxydeoxyguanosine immunohistochemistry also revealed microvascular as well as neuronal oxidative DNA damage. These results provide new insights into the pathogenesis of cognitive dysfunction in SAH. They reveal a surprisingly prolonged time course of diffuse cerebrovascular insufficiency, most likely due to reversible microvascular dysfunction. Similar to findings in experimental models of vascular dementia, the data indicate a potentially important role for prolonged cerebrovascular insufficiency, probably due to microvascular dysfunction, and selective cortical and subcortical neuronal loss in cognitive failure following SAH.
Takata
Ken
K
Department of Anesthesiology, Multidisciplinary Neuroprotection Laboratories, Duke University Medical Center, Durham, NC 27710, USA.
Sheng
Huaxin
H
Borel
Cecil O
CO
Laskowitz
Daniel T
DT
Warner
David S
DS
Lombard
Frederick W
FW
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000473:pathology*; D013995:Time