Inflammation and inflammatory cell recruitment in acute cerebrovascular diseases

Abstract

Inflammation seems to play a major role in the pathogenesis of ischemic stroke as well as in other forms of brain damage. Ischemic brain injury induces a strong inflammatory response that begins in the microcirculation and involves several cell types and molecules, leading to neuronal death. The immune system is actively involved in the pathogenesis of acute brain damage through a set of events that include leukocyte and monocyte infiltration into the brain, activation of resident cells, including microglia, astrocytes and endothelial cells, and the elevated production of several inflammatory molecules, such as cytokines, that together play a complex role in the pathophysiology of ischemic brain damage, as illustrated in animal models and stroke patients. These immune cells are activated and recruited in damaged tissues at different times. Immunity and inflammation are thus key elements in the pathogenic processes of acute cerebral ischemia, and therefore the use of anti-inflammatory therapeutic strategies to antagonize inflammatory mechanisms triggered by cerebral ischemia may improve the outcome of stroke. Several drugs have been produced to counteract inflammation. However, while they have proven effective in animal models of stroke they have not been successful in clinical trials because of unacceptable side-effects. Although several aspects of the inflammatory cerebral response to ischemia are still unclear and many questions have not been answered yet, it is clear that inflammation plays an important role and represents an integral part of the complex pathogenic mechanisms that characterize stroke, and therefore the study of inflammatory responses to post-ischemia and the development of agents able to counteract it represent the future of treating ischemic stroke. In this primer we will reexamine some aspects of involvment of inflammatory cells in cerebrovascular disease.