Neuroinflammation after acute ischemic stroke: a volcano hard to contain

Abstract

Many endogenous, exogenous and systemic factors individually can lead to occlusive vessel pathology affecting the neuroendovascular unit compromising cerebral blood flow. The brain ischemia thus created irrespective of the pathology has similar endpoint and involves blood vessels, astrocytes, neurons and surrounding microglia triggering the whole spectrum of neuroinflammation which is an important component in the ischemic cascade. The resultant series of neuroinflammatory reactions cause depolarization of neuronal cells and activation of pro-inflammatory cellular agents and subsequently cell death. Neuroinflammation can be an effect and (or) cause of acute energy failure, excitotoxicity, ionic imbalance, channel dysfunctions, and oxidative free radicals in the central nervous system. Non-restoration of the blood flow within the threshold period can result in an extensive brain damage from activation of deadly latent proteases like matrix metalloprotease, and immediate early genes destroying the neuronal microenvironment and blood brain barrier. It is paradoxical that both deoxygenation and reoxygenation can contribute significantly to the stroke neuroinflammatory injury. The cascade of cerebral injury also involves activation of microglia and astrocytes leading to release of chemical mediators like cytokines, oxygen free radicals, neurotoxic and neurotropic factors further contributing to the damage. Neutrophil activation and binding to endothelial surface using adhesion molecules and their subsequent transmigration to the ischemic core will enhance the injury. Monocyte and macrophage will also play a role in brain injury by its release of cytokine and transformation into phagocytes. Strategy to target various players of neuroinflammation to halt or minimize the cerebral damage concentrate on inhibiting intracellular adhesion molecules (ICAMs), vascular cell adhesion molecules (VCAMs), neutrophils, microglia, major histocompatibility complex (MHC), cytokine, chemokine and free radical scavenger system. Different strategies to suppress inflammation secondary to ischemia have shown promise in experimental environment but have failed to demonstrate successful clinical translation and further studies are underway. However, this knowledge of neuroinflammation becomes crucial in developing novel therapies for neuroprotection and broadening the field of therapeutic options for cerebral ischemia which is currently limited. In this brief review we try to address diverse mechanisms involving neuroinflammation in relation to ischemic stroke.

doi:10.3969/j.issn.1672-6731.2013.11.011