Pathophysiologic cascades in ischemic stroke

Abstract

Many advances have been achieved in terms of understanding the molecular and cellular mechanisms of ischemic stroke. But thus far, clinically effective neuroprotectants remain elusive. In this minireview, we summarize the basics of ischemic cascades after stroke, covering neuronal death mechanisms, white matter pathophysiology, and inflammation with an emphasis on microglia. Translating promising mechanistic knowledge into clinically meaningful stroke drugs is very challenging. An integrative approach that encompasses the multimodal and multicell signaling phenomenon of stroke will be required to move forward.

Fig. 1

Schematic showing the nonlinear and highly integrative aspects of stroke pathophysiology. Mechanisms can be manifested at multiple levels of phenomenology, ranging from molecular and cellular biology to whole animal physiology and pharmacology to individual human subjects and population responses. The influence of genetics and risk factors adds to this complexity. And ultimately, these multifactorial processes connect into spatial and temporal gradients of tissue injury and repair. Altogether, this matrix represents a series of hurdles that must be considered before translation can take place. Finding clinically effective therapeutics for stroke prevention, treatment, and recovery is challenging. Multitarget integrative solutions may be required.