ROLE OF ANGIOGENESIS IN PATIENTS WITH CEREBRAL ISCHEMIC STROKE

Background and Purpose Stroke is one of the most common causes of mort ality and morbidity in the Western world. It results from the occlusio n 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 imped ed the logical development of therapy. Methods Brains were obtained fr om 10 patients aged 46 to 85 years with survival times of 5 to 92 days after their stroke. Infarcted areas and representative control tissue s from the contralateral uninvolved brain hemisphere were collected. M icrovessel density was measured microscopically. A total of 6520 micro vessels were scored in 10 801 areas. The level of activation of the en dothelial cells was studied by immunohistochemistry using three monocl onal antibodies, viz, E-9, raised against activated endothelial cells; IG11, recognizing vascular cell adhesion molecule-1; and anti-prolife rating cell nuclear antigen. Angiogenic activity in tissue extracts wa s examined using an in vivo chicken chorioallantoic membrane assay. Re sults There was a statistically significant increase in the number of microvessels (Wilcoxon log-rank test; P less than or equal to.01) in 9 of 10 infarcted brain tissues when compared with their contralateral normal hemisphere. In these patients the higher blood vessel counts co rrelated with longer survival, as ascertained by Spearman's rho analys is (P<.02). The number of microvessels filled with blood cells was sig nificantly lower in the infarcted hemispheres (P<.01). In contrast, st atistically significant increased numbers of empty microvessels occurr ed in infarcted tissues compared with the contralateral hemisphere. Mo noclonal antibody E-9 reacted weakly with normal-brain vascular endoth elial cells; anti-proliferating cell nuclear antigen and IG11 were vir tually negative. All three antibodies strongly stained the blood vesse ls 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 an giogenesis that is more developed in the penumbra. Further experiments are needed to determine if this angiogenesis has beneficial effect.