Stroke, Vol 25, 1794-1798, Copyright © 1994 by American Heart Association
J Krupinski, J Kaluza, P Kumar, S Kumar and JM Wang
BACKGROUND AND PURPOSE: Stroke is one of the most common causes of
mortality and morbidity in the Western world. It results from the occlusion
of a cerebral artery followed by severe disturbances in blood supply
through microvessels to brain tissue. Despite an extensive literature its
pathophysiology is poorly understood, and this has severely impeded the
logical development of therapy. METHODS: Brains were obtained from 10
patients aged 46 to 85 years with survival times of 5 to 92 days after
their stroke. Infarcted areas and representative control tissues from the
contralateral uninvolved brain hemisphere were collected. Microvessel
density was measured microscopically. A total of 6520 microvessels were
scored in 10,801 areas. The level of activation of the endothelial cells
was studied by immunohistochemistry using three monoclonal antibodies, viz,
E-9, raised against activated endothelial cells; IG11, recognizing vascular
cell adhesion molecule-1; and anti-proliferating cell nuclear antigen.
Angiogenic activity in tissue extracts was examined using an in vivo
chicken chorioallantoic membrane assay. RESULTS: There was a statistically
significant increase in the number of microvessels (Wilcoxon log-rank test;
P < or = .01) in 9 of 10 infarcted brain tissues when compared with
their contralateral normal hemisphere. In these patients the higher blood
vessel counts correlated with longer survival, as ascertained by Spearman's
p analysis (P < .02). The number of microvessels filled with blood cells
was significantly lower in the infarcted hemispheres (P < .01). In
contrast, statistically significant increased numbers of empty microvessels
occurred in infarcted tissues compared with the contralateral hemisphere.
Monoclonal antibody E-9 reacted weakly with normal-brain vascular
endothelial cells; anti-proliferating cell nuclear antigen and IG11 were
virtually negative. All three antibodies strongly stained the blood vessels
of stroke tissues. The stroke tissues contained angiogenic activity, as
shown by the induction of new blood vessels in a chorioallantoic membrane
assay. CONCLUSIONS: We have shown that stroke causes active angiogenesis
that is more developed in the penumbra. Further experiments are needed to
determine if this angiogenesis has beneficial effect.
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Role of angiogenesis in patients with cerebral ischemic stroke
Department of Neuropathology, Jagiellonian University, Krakow, Poland.
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