The cerebral microcirculation in ischemia and hypoxemia. The Arisztid G. B. Kovách Memorial Lecture.

Abstract

The cerebral capillary circulation exhibits heterogenous perfusion and undergoes characteristic changes in the distribution of RBC flow in response to systemic physiological stimuli. Hypoxemia, hypercapnia and hypotension increase the homogeneity of capillary perfusion, which is thought to preserve or enhance transcapillary exchange. Redistribution of capillary RBC flow between nutritive capillaries and preferential channels may contribute to this response. Selective changes in capillary flow may be brought about by non-smooth muscle-based contractile or blood-borne mechanisms. Isovolemic hemodilution anemia increases RBC velocity and supply rate with no decrease in capillary hematocrit. The effect of cerebral ischemia on microvascular patency depends on the severity and time course of the insult and whether the injury is global or focal. Capillary plugging is not observed following transient forebrain ischemia in the rat cerebral cortex but may contribute to tissue injury prior to reperfusion and during prolonged and severe ischemia. In the future, a better understanding of the functional architecture of the cerebral capillary network and its significance in the adaptation to altered circulatory conditions will continue to be an important goal of research. More work will have to be done to (i) substantiate the postulated physiological regulation of cerebral capillary flow, (ii) determine the cellular mechanism of integration of flow-dependent and neuronal activity-dependent signals, and (iii) identify the principal mediators, their cellular sources and molecular targets. The final answer to these questions will in a large part depend on our ability to directly, i.e. microscopically, visualize microvascular, neuronal and molecular phenomena as they occur in the brain in a spatially and temporally distributed manner.