title: The Role of Activated Microglia and Resident Macrophages in the Neurovascular Unit during Cerebral Ischemia: Is the Jury Still Out?
abstract: Paracrine signaling in the neurovascular unit (NVU) is aimed to adjust the supply of oxygen and nutrients to metabolic demands of the brain in a feed-forward manner. Cerebral ischemia (CI) severely disrupts this homeostatic mechanism and also causes activation of microglia and resident macrophages in the brain. Contradictory data exist on the time pattern of microglial activation and polarization during CI, on molecular mechanisms that trigger them and on effects of microglia-derived cytokines on brain cells. It appears that conditions that occur during transient ischemia or in the penumbra of focal ischemia in vivo or equivalent conditions in vitro trigger polarization of resting microglia/macrophages into the M2 phenotype, which mainly exerts anti-inflammatory and protective effects in the brain, while prolonged ischemia with abundant necrosis promotes microglial polarization into the M1 phenotype. During the later stages of recovery, microglia that polarized initially into the M2 phenotype can shift into the M1 phenotype. Thus, it appears that cells with both phenotypes are present in the affected area, but their relative amount changes in time and probably depends on the proximity to the ischemic core. It was assumed that cells with the M1 phenotype exert detrimental effects on neurons and contribute to the blood-brain barrier opening. Several M1 phenotype-specific cytokines exert protective effects on astrocytes, which could be important for reactive gliosis occurring after ischemia. Thus, whether or not suppression of microglial activity after CI is beneficial for neurological outcome still remains unclear and current evidence suggests that no simple answer could be given to this question.
authors: Department of Physiology, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait.
authors: Rawan
authors: R
authors: Barakat
authors: Zoran
authors: Z
authors: Redzic
mesh_terms: D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008262:Macrophage Activation / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism / Q000473:pathology*