A study on blood-brain barrier ultrastructural changes induced by cerebral hypoperfusion of different stages.
OBJECTIVE
To evaluate the ultrastructural changes in the blood-brain barrier (BBB) induced by cerebral hypoperfusion of different stages, which may predispose the brain to the formation of vasogenic edema and hemorrhage under cerebral luxury perfusion.


METHODS
Twenty cerebral steal models with left neck arteriovenous fistula (AVF) were surgically created in Wistar's rats, leading to a noninfarctional reduction in the cerebral blood flow (CBF) by between 25 and 50%, resulting in cerebral hypoperfusion in the AVF side for 3 days (acute stage), 3 weeks (subacute stage) and 3 months (chronic stage), respectively. Another six sham-operated models were made in age-matched rats as control. The BBB ultrastructural changes were assessed by transmission electron microscopy. Ridit analysis was conducted to compare the positive ratio of ultrastructural changes among multiple groups.


RESULTS
Electron microscopy demonstrated no ultrastructural change at the acute stage, however, at the subacute stage, slight vacuolar degeneration was found in the astrocytic foot process layer encircling the capillaries; furthermore, at the chronic stage, the astrocytic foot processes expressed marked vacuolization associated with the adjacent astrocytic degeneration. Meanwhile, in both capillary endothelium and basal lamina layers, no abnormal ultrastructures similar to those in the astrocytic foot processes layer were identified. After cerebral luxury perfusion took place, BBB was disrupted where astrocytic foot processes vacuolization was most distinguished.


CONCLUSIONS
Astrocytes generate ultrastructural abnormality as a result of chronic cerebral hypoperfusion. Astrocytic foot process vacuolization, which constitutes the major ultrastructural change in the BBB, is the extension of the degeneration of astrocyte body. It is inferred that BBB is prone to structure weakness and function instability, which forms the morphological basis of cerebral luxury perfusion.
Wu
Jin-Song
JS
Department of Neurosurgery, Huashan Hospital, Shanghai Medical School, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, China. wjsongc@online.sh.cn
Chen
Xian-Cheng
XC
Chen
Hong
H
Shi
Yu-Quan
YQ
D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000648:ultrastructure; D001812:Blood-Brain Barrier / Q000473:pathology / Q000648:ultrastructure*; D002545:Brain Ischemia / Q000209:etiology* / Q000473:pathology*; D002908:Chronic Disease; D004195:Disease Models, Animal; D002538:Intracranial Arteriovenous Malformations / Q000150:complications* / Q000473:pathology; D046529:Microscopy, Electron, Transmission / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013997:Time Factors