10 - Inflammation and Immune Response

Abstract

Ischemic stroke triggers an inflammatory response that progresses for days to weeks and involves both tissue resident and peripheral immune cells. There is evidence that the acute inflammatory response contributes to the progression of ischemic brain injury, that ultimately exacerbates neurologic deficits. On the other hand, recent research points at a more multifaceted role of immune cells in brain ischemia, where immune cells participate in repair processes during the subacute and chronic stages. In addition, the interaction of the ischemic brain and the immune system is bidirectional, and while the peripheral immune system supplies immune cells that participate in the local inflammatory response, neural and humoral factors generated by the ischemic brain signal to the peripheral immune system leading to an acute systemic inflammatory response followed by immunosuppression and increased risk for nosocomial infections. Understanding these processes and the nature of immune cells involved during deleterious and reparatory phases of postischemic inflammation will be necessary to devise effective therapeutic strategies for human stroke. In this chapter, we review the features of postischemic inflammation, focusing on recent advances and insights on the potential molecular and cellular mechanisms by which such inflammation influences stroke pathophysiology. Furthermore, we examine the role of bidirectional signaling between the ischemic brain and the peripheral immune system in determining stroke outcome. Finally, we analyze the potential therapeutic implications of modulators of specific inflammatory targets from the perspective of near-future translational approaches.