The biphasic function of microglia in ischemic stroke

Ma, Yuanyuan; Wang, Jixian; Wang, Yongting; Yang, Guo‐Yuan

doi:10.1016/j.pneurobio.2016.01.005

Cited by 573 publications

(563 citation statements)

References 374 publications

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“…Although very dense material can invoke a foreign body response in the brain that leads to an encapsulation of material by fibrotic scarring [44], injections of hydrogels typically exhibit a reduced microglia and astrocytes response compared to just needle track damage [43]. Although microglia and astrocytes are abundantly present in the peri-cavity tissue [45], more neurons and oligodendrocytes invaded the ECM hydrogels than astrocytes within 24 h of injection. The reciprocity in interaction between hydrogel and host brain is essential to determine the host tissue response and guide cell invasion or induce further scarring and a foreign body response [46].…”

Section: Discussionmentioning

confidence: 99%

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

et al. 2016

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Brain tissue loss following stroke is irreversible with current treatment modalities. The use of an acellular extracellular matrix (ECM), formulated to produce a hydrogel in situ within the cavity formed by a stroke, was investigated as a method to replace necrotic debris and promote the infiltration of host brain cells. Based on magnetic resonance imaging measurements of lesion location and volume, different concentrations of ECM (0, 1, 2, 3, 4, 8 mg/mL) were injected at a volume equal to that of the cavity (14 days post-stroke). Retention of ECM within the cavity occurred at concentrations >3 mg/mL. A significant cell infiltration into the ECM material in the lesion cavity occurred with an average of ~36,000 cells in the 8 mg/mL concentration within 24 h. An infiltration of cells with distances of >1500 μm into the ECM hydrogel was observed, but the majority of cells were at the tissue/hydrogel boundary. Cells were typically of a microglia, macrophage, or neural and oligodendrocyte progenitor phenotype. At the 8 mg/mL concentration ~60% of infiltrating cells were brain-derived phenotypes and 30% being infiltrating peripheral macrophages, polarizing toward an M2-like anti-inflammatory phenotype. These results suggest that an 8 mg/mL ECM concentration promotes a significant acute endogenous repair response that could potentially be exploited to treat stroke.

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Section: Discussionmentioning

confidence: 99%

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

et al. 2016

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“…In later stages, these inflammatory cells function to remove debris and clear injured myocardium of dead cells and facilitate healing. Microglia are the brain’s resident macrophages and like cardiac macrophages and hepatic Kupffer cells exhibit a biphasic polarization during reperfusion, first contributing to tissue injury and then facilitating repair (524a). Similar divergent roles for macrophages have been reported in organ transplantation (679a).…”

Section: Cell Types Involved In Postischemic Inflammationmentioning

confidence: 99%

Ischemia/Reperfusion

Kalogeris

Baines

Krenz

et al. 2016

Comprehensive Physiology

626

565

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Ischemic disorders, such as myocardial infarction, stroke, and peripheral vascular disease, are the most common causes of debilitating disease and death in westernized cultures. The extent of tissue injury relates directly to the extent of blood flow reduction and to the length of the ischemic period, which influence the levels to which cellular ATP and intracellular pH are reduced. By impairing ATPase-dependent ion transport, ischemia causes intracellular and mitochondrial calcium levels to increase (calcium overload). Cell volume regulatory mechanisms are also disrupted by the lack of ATP, which can induce lysis of organelle and plasma membranes. Reperfusion, although required to salvage oxygen-starved tissues, produces paradoxical tissue responses that fuel the production of reactive oxygen species (oxygen paradox), sequestration of proinflammatory immunocytes in ischemic tissues, endoplasmic reticulum stress, and development of postischemic capillary no-reflow, which amplify tissue injury. These pathologic events culminate in opening of mitochondrial permeability transition pores as a common end-effector of ischemia/reperfusion (I/R)-induced cell lysis and death. Emerging concepts include the influence of the intestinal microbiome, fetal programming, epigenetic changes, and microparticles in the pathogenesis of I/R. The overall goal of this review is to describe these and other mechanisms that contribute to I/R injury. Because so many different deleterious events participate in I/R, it is clear that therapeutic approaches will be effective only when multiple pathologic processes are targeted. In addition, the translational significance of I/R research will be enhanced by much wider use of animal models that incorporate the complicating effects of risk factors for cardiovascular disease.

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“…They secrete cytokines, chemokines and adhesion molecules. These inflammatory factors increase BBB permeability, further elevate endothelial adhesion molecule expression and recruit the peripheral immune cells into the injury site (Hu et al, 2014; Ma et al, 2016). Inflammation-induced BBB dysfunction is one of the key mechanisms underlying acute brain damage after ischemic stroke.…”

Section: Vulnerability Of Aged Nvu To Ischemic Strokementioning

confidence: 99%

Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect

Cai

Zhang

et al. 2017

Ageing Research Reviews

229

184

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Current understanding on the mechanisms of brain injury and neurodegeneration highlights an appreciation of multicellular interactions within the neurovascular unit (NVU), which include the evolution of blood-brain barrier (BBB) damage, neuronal cell death or degeneration, glial reaction, and immune cell infiltration. Aging is an important factor that influences the integrity of the NVU. The age-related physiological or pathological changes in the cellular components of the NVU have been shown to increase the vulnerability of the NVU to ischemia/reperfusion injury or neurodegeneration, and to result in deteriorated brain damage. This review describes the impacts of aging on each NVU component and discusses the mechanisms by which aging increases NVU sensitivity to stroke and neurodegenerative diseases. Prophylactic or therapeutic perspectives that may delay or diminish aging and thus prevent the incidence of these neurological disorders will also be reviewed.

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The biphasic function of microglia in ischemic stroke

Cited by 573 publications

References 374 publications

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

ECM hydrogel for the treatment of stroke: Characterization of the host cell infiltrate

Ischemia/Reperfusion

Dysfunction of the neurovascular unit in ischemic stroke and neurodegenerative diseases: An aging effect

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