Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain

Lalancette–Hébert, Mélanie; Gowing, Genevíève; Simard, Alain R.; Weng, Yuan Cheng; Križ, Jasna

doi:10.1523/jneurosci.5360-06.2007

Cited by 801 publications

(710 citation statements)

References 54 publications

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“…Faustino et al [63] also reported that microglia depletion enhances inflammation and injury in acute neonatal focal stroke. Selective ablation of proliferating microglia after focal ischemia in a transgenic mouse also demonstrated exacerbation of stroke injury with an altered inflammatory response [64]. A similar beneficial effect of microglia in stroke was reported in a study where there was a 60 % increase in infarct size by selective elimination of microglia, which the effect was reversed by repopulating the cells [65].…”

Section: Microgliasupporting

confidence: 60%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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Historically, the brain has been considered an immune-privileged organ separated from the peripheral immune system by the blood-brain barrier. However, immune responses do occur in the brain in neurological conditions in which the integrity of the blood-brain barrier is compromised, exposing the brain to peripheral antigens and endogenous danger signals. While most of the associated pathological processes occur in the central nervous system, it is now clear that peripheral immune cells, especially mononuclear phagocytes, that infiltrate into the injury site play a key role in modulating the progression of primary brain injury development. As inflammation is a necessary and critical component for the subsequent injury resolution process, understanding the contribution of mononuclear phagocytes on the regulation of inflammatory responses may provide novel approaches for potential therapies. Furthermore, predisposed comorbid conditions at the time of stroke cause the alteration of stroke-induced immune and inflammatory responses and subsequently influence stroke outcome. In this review, we summarize a role for microglia and monocytes/macrophages in acute ischemic stroke in the context of normal and metabolically compromised conditions.

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Section: Microgliasupporting

confidence: 60%

Microglia and Monocyte-Derived Macrophages in Stroke

2016

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“…36 Among the potential factors that might have prevented their use in inflammatory conditions is that broad suppression of microglia/ macrophages may deprive the brain of their normal phagocytic roles and cause the buildup of cellular debris. This notion is supported by observations that selective depletion of proliferative microglia exacerbate brain injuries 24,37 and, conversely, that injections of exogenous microglia into the brain ameliorate CNS injuries. 38,39 Many authors have concluded that acute inflammation serves several protective functions, 16 whereas chronic inflammation exacerbates injury.…”

Section: Discussionmentioning

confidence: 80%

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

Wang

Zhang

et al. 2013

J Cereb Blood Flow Metab

408

331

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Mononuclear phagocytes are a population of multi-phenotypic cells and have dual roles in brain destruction/reconstruction. The phenotype-specific roles of microglia/macrophages in traumatic brain injury (TBI) are, however, poorly characterized. In the present study, TBI was induced in mice by a controlled cortical impact (CCI) and animals were killed at 1 to 14 days post injury. Real-time polymerase chain reaction (RT-PCR) and immunofluorescence staining for M1 and M2 markers were performed to characterize phenotypic changes of microglia/macrophages in both gray and white matter. We found that the number of M1-like phagocytes increased in cortex, striatum and corpus callosum (CC) during the first week and remained elevated until at least 14 days after TBI. In contrast, M2-like microglia/macrophages peaked at 5 days, but decreased rapidly thereafter. Notably, the severity of white matter injury (WMI), manifested by immunohistochemical staining for neurofilament SMI-32, was strongly correlated with the number of M1-like phagocytes. In vitro experiments using a conditioned medium transfer system confirmed that M1 microglia-conditioned media exacerbated oxygen glucose deprivation-induced oligodendrocyte death. Our results indicate that microglia/macrophages respond dynamically to TBI, experiencing a transient M2 phenotype followed by a shift to the M1 phenotype. The M1 phenotypic shift may propel WMI progression and represents a rational target for TBI treatment.

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“…P2X7R knock-out studies in autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, have also shown a significant reduction in the protein levels of IL-1 and IL-6 with a concomitant decrease in lymphocytic apoptosis which, in turn, exacerbates the susceptibility to the disorder [79]. Similarly, a change in the pro-inflammatory profile by selective ablation of proliferating microglial cells exacerbates cell death and injury in the ischemic brain [80]. Thus, whereas interleukins levels are associated to inflammation, they are also important mediators in neuroprotection of the damaged tissues.…”

Section: Neuronal P2x7r In Spinal Cord Injurymentioning

confidence: 99%

Physiological and pathological functions of P2X7 receptor in the spinal cord

Cotrina

Nedergaard

2009

Purinergic Signalling

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ATP-mediated signaling has widespread actions in the nervous system from neurotransmission to regulation of proliferation. In addition, ATP is released during injury and associated to immune and inflammatory responses. Still, the potential of therapeutic intervention of purinergic signaling during pathological states is only now beginning to be explored because of the large number of purinergic receptors subtypes involved, the complex and often overlapping pharmacology and because ATP has effects on every major cell type present in the CNS. In this review, we will focus on a subclass of purinergic-ligand-gated ion channels, the P2X7 receptor, its pattern of expression and its function in the spinal cord where it is abundantly expressed. We will discuss the mechanisms for P2X7R actions and the potential that manipulating the P2X7R signaling pathway may have for therapeutic intervention in pathological events, specifically in the spinal cord.

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Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain

Cited by 801 publications

References 54 publications

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia and Monocyte-Derived Macrophages in Stroke

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

Physiological and pathological functions of P2X7 receptor in the spinal cord

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