Ischemia and stroke

Abstract

Ischemic stroke is a complex brain pathology caused by an interruption of blood supply to the brain. It is associated with neurological deficits (paralysis, memory disturbances, and thinking, language, and movement deficits), which reflect the localization and the size of the compromised brain area, and that are the manifestation of complex cellular events triggered by energy depletion. The major pathogenic events involved are excitotoxicity, peri-infarct neuronal depolarization, inflammation, oxidative stress, and apoptosis. Inflammation plays a prominent role, worsening the injury in the early phase and influencing post-stroke recovery in the late phase. Activated microglia are one of the most important cellular components of post-stroke inflammation, appearing from the first few hours after hypoxic-ischemic injury and persisting for days and weeks thereafter. Activation of microglia could be the major cause of delayed neuronal cell death: microglial harmful actions range from the release of reactive oxygen species (ROS) and nitric oxide (NO) to pro-inflammatory cytokines and matrix metalloproteinases (MMPs). In addition, microglia responses including phagocytosis of cell debris, remodeling of the extracellular matrix as well as the release of cytokines and trophic factors can improve the outcome of stroke. This knowledge opens a dynamic and possible time-dependent role of microglia in the brain response to ischemic injury. In this chapter, we will discuss the nature of the inflammatory response in the hypoxic-ischemic brain, the contribution of microglia to injury and to regenerative processes after stroke, and finally, how cerebral ischemia directly affect microglial functions and survival.