Blood Flow, Energy Failure, and Vulnerability to Stroke

Abstract

In recent years, the study of mechanisms of ischemic neuronal injury has focused on the cascade of intracellular events triggered by ischemic conditions, emphasizing the role of glutamate receptor activation. The focus on intracellular mechanisms has led to an approach of identifying individual mechanisms of injury in simple systems and then examining their role in more intact systems. Rarely, however, are these mechanisms placed into their proper context as events that occur during reduced blood flow, interacting with cellular energy status. Simple models of ischemic injury based on one or two of these basic mechanisms do not reflect what is known about the dynamics of blood flow and metabolism in ischemia. For example, it has been suggested that at the point of energy failure, there is massive release of glutamate into the extracellular space, triggering a cascade that resembles glutamate toxicity. Although glutamate receptors certainly play an important role in mediating ischemic neuronal injury, blockade of glutamate receptors has no effect in some models. In other models, glutamate toxicity can be observed in the absence of massive glutamate release. Thus, whereas glutamate receptors are often critical mediators of ischemic neuronal injury, energy failure and reperfusion are fundamental factors as well.