Stroke, Vol 25, 1847-1853, Copyright © 1994 by American Heart Association
Y Okada, BR Copeland, R Fitridge, JA Koziol and GJ del Zoppo
BACKGROUND AND PURPOSE: Ischemic cerebral injury is associated with
activation of the blood coagulation cascade. To elucidate the contribution
of fibrin formation to microvascular injury during focal cerebral ischemia
and reperfusion, we have studied the time course and the localization of
fibrin deposition in cerebral microvessels and the surrounding tissues
during ischemia/reperfusion in a well-described nonhuman primate model.
METHODS: Cerebral tissues from adolescent male baboons were examined after
2-hour middle cerebral artery occlusion (n = 3) and after 3 hours of middle
cerebral artery occlusion and 1-hour (n = 6), 4-hour (n = 3), and 24-hour
(n = 4) reperfusion; tissues from control primates (n = 3) also were
examined. Fibrin deposition was detected by immunohistochemical techniques
using the fibrin-specific monoclonal antibody MH-1. The number and size
distribution of microvessels associated with fibrin were quantified by
video-imaging microscopy. RESULTS: Fibrin was associated with microvessels
only in the ischemic zone where severe neuronal injury was documented, its
frequency increasing with the reperfusion period (F4,26 = 3.80, P <
.05). Extravascular fibrin deposition was significantly increased by 24-
hour reperfusion compared with the other subjects (P < .05). Preischemia
infusion of the anti-tissue factor monoclonal antibody TF9- 6B4 resulted in
significant reduction of intramicrovascular fibrin (P < .038 versus no
intervention) at 1-hour reperfusion but had no effect on extravascular
fibrin deposition. CONCLUSIONS: These results suggest that microvascular
fibrin deposition accumulates in a time-dependent manner during focal
cerebral ischemia/reperfusion and that exposure of focal cerebral
ischemia/reperfusion and that exposure of plasma to perivascular tissue
factor is partially responsible for occlusion formation. During ischemia
the large plasma protein fibrinogen extravasates and interacts with
parenchymal tissue factor, forming significant extravascular fibrin by 24
hours of reperfusion.
ARTICLES
Fibrin contributes to microvascular obstructions and parenchymal changes during early focal cerebral ischemia and reperfusion
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif. 92037.
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