Vascular aspects and hemodynamic consequences of central nervous system injury.

We document here microvascular alterations occurring in models of mild, moderate, and severe cerebral ischemic injury. The relationship of the vascular abnormalities to the generation of hemodynamic alterations was also evaluated. Following periods of severe incomplete ischemia, scanning electron microscopic analysis of cerebral microvessels revealed the widespread production of cerebral endothelial microvilli. These microvilli increased in frequency as the ischemic insult was prolonged and remained prominent during periods of recirculation. Although these luminal projections would not be expected to inhibit reperfusion completely, they might increase microvascular resistance, leading to moderate hemodynamic impediments extending into the post-ischemic period. Similar periods of complete ischemia resulted in more severe microvascular alterations. Light and electron microscopic studies revealed a high frequency of compressed capillary lumina with vascular stasis. These compressed vessels were consistently surrounded by swollen astrocytic foot processes. When recirculation was instituted for 1 hr following 1 hr of complete ischemia, regions of non-perfusion were detected autoradiographically within brain regions destined to undergo ischemic infarction. Finally, in an attempt to determine the consequences of a primary microvascular insult on brain structure and function, the endothelial layer of microvessels in the cerebral cortex was injured using a noninvasive photochemical method. Endothelial damage led to platelet aggregation in both pial and intraparenchymal vessels. Occlusive thrombi were frequently detected with perivascular edema associated with vascular compression and severe focal ischemia. Ultrastructural blood-brain barrier studies using the horseradish peroxidase tracer demonstrated that protein leakage at the site of primary vascular injury resulted in tracer material in brain regions remote from the pathological lesion. The widespread leakage of protein tracer was associated with decreased blood flow in remote brain regions at several postirradiation periods. These data emphasize the importance of injury-induced microvascular dysfunction in the generation of brain lesions and hemodynamic abnormalities.