Microglial Responses after Ischemic Stroke and Intracerebral Hemorrhage

Abstract

Stroke is a leading cause of death worldwide. Ischemic stroke is caused by blockage of blood vessels in the brain leading to tissue death, while intracerebral hemorrhage (ICH) occurs when a blood vessel ruptures, exposing the brain to blood components. Both are associated with glial toxicity and neuroinflammation. Microglia, as the resident immune cells of the central nervous system (CNS), continually sample the environment for signs of injury and infection. Under homeostatic conditions, they have a ramified morphology and phagocytose debris. After stroke, microglia become activated, obtain an amoeboid morphology, and release inflammatory cytokines (the M1 phenotype). However, microglia can also be alternatively activated, performing crucial roles in limiting inflammation and phagocytosing tissue debris (the M2 phenotype). In rodent models, microglial activation occurs very early after stroke and ICH; however, their specific roles in injury and repair remain unclear. This review summarizes the literature on microglial responses after ischemic stroke and ICH, highlighting the mediators of microglial activation and potential therapeutic targets for each condition.

Lack of chronic neuroinflammation in the absence of focal hemorrhage in a rat model of low-energy blast-induced TBI

“…Microglia are activated by thrombin through MAPK signaling pathways via the proteinase-activated receptor-1 (PAR-1) [16,39]. Microglia can also be activated through Toll-like receptors (TLRs) and the receptor for advanced glycosylation endproducts via danger-associated molecular signals (ATP, neurotransmitters, nucleic acids, heat shock proteins, and high-mobility group box 1 proteins) released by necrotic cells [10,40,52]. Microglial activation leads to increased production of TNF-α and IL-1β, which induces neuronal apoptosis [57].…”

Dominant role of microglial and macrophage innate immune responses in human ischemic infarcts

“…Furthermore, molecules involved in controlling iron homeostasis were highly up-regulated, which may in part reflect the age related iron accumulation in the normal human brain and its liberation in lesions of a diseased brain (21). On the contrary, antigens which are associated with anti-inflammatory activation of macrophages, such as CD163 and CD206, peaked at later lesion stages (late resorption stage), which is in part different in timing as described before in experimental models (26,55). In peripheral blood, the ratio between pro-and anti-inflammatory macrophages may predict clinical course and prognosis in human stroke patients (57).…”

A20 Ameliorates Intracerebral Hemorrhage–Induced Inflammatory Injury by Regulating TRAF6 Polyubiquitination

“…Previous studies have indicated that inflammation plays a key role in ICH-induced secondary injury and that microglia activation, peripheral inflammatory cell infiltration, and the release of proinflammatory factors all participate in the pathogenesis of inflammation (4,5). Most previous studies have focused on the role of inflammatory factors.…”

Immunopathogenetic Aspects of Ischemic Stroke

“…Медицинская Иммунология ных медиаторов -интерлейкина-10, (IL-10), трансформирующего фактора роста β (TGF-β), IL-4, IL-13, а также инсулиноподобного фактора роста-1 (IGF-1) и различных нейротрофических факторов [119]. При очаговой церебральной ише-мии микроглия в раннем периоде экспрессирует М2-фенотип, однако впоследствии подвергнутые ишемии нейроны проградиентно индуцируют поляризацию микроглии в М1-клетки, усилива-ющие гибель нейронов [46].…”

“…Следует отметить, что активация микроглии достигает пика на 2-3 сутки и персистирует не-сколько недель [25,119]. В эти сроки (хрониче-ская фаза ишемического инсульта) включаются восстановительные механизмы, направленные на ограничение воспаления и стимуляцию ак-сонального ремоделирования нервной ткани, требующие участия М2-микроглии [29].…”