Attenuation of Acute Intracerebral Hemorrhage-Induced Microglial Activation and Neuronal Death Mediated by the Blockade of Metabotropic Glutamate Receptor 5 In Vivo

Rahman, Saidur; Yang, Jianbo; Luan, Yan; Qiu, Zhengguo; Zhang, Jianshui; Lü, Haixia; Chen, Xinlin; Liu, Yong

doi:10.1007/s11064-020-03006-1

Cited by 11 publications

(4 citation statements)

References 62 publications

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“…Glutamate receptors (mGluRs) are also considered as microglial-related targets in brain ischemia. It is known that blockage or ablation of mGluR5 reduces acute microglial activation and promotes neuroprotection and neurofunctional recovery [ 49 , 50 ]. On the other hand, purinergic receptors, like P2X4R, P2X7R, and P2Y6R, have been related to neuroprotection mediated by microglia after brain ischemia owing to their anti-inflammatory effects [ 51 , 52 ].…”

Section: Microgliamentioning

confidence: 99%

Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

Hernández

Villa-González

Martín

et al. 2021

Cells

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Ischemic stroke is the second cause of mortality and the first cause of long-term disability constituting a serious socioeconomic burden worldwide. Approved treatments include thrombectomy and rtPA intravenous administration, which, despite their efficacy in some cases, are not suitable for a great proportion of patients. Glial cell-related therapies are progressively overcoming inefficient neuron-centered approaches in the preclinical phase. Exploiting the ability of microglia to naturally switch between detrimental and protective phenotypes represents a promising therapeutic treatment, in a similar way to what happens with astrocytes. However, the duality present in many of the roles of these cells upon ischemia poses a notorious difficulty in disentangling the precise pathways to target. Still, promoting M2/A2 microglia/astrocyte protective phenotypes and inhibiting M1/A1 neurotoxic profiles is globally rendering promising results in different in vivo models of stroke. On the other hand, described oligodendrogenesis after brain ischemia seems to be strictly beneficial, although these cells are the less studied players in the stroke paradigm and negative effects could be described for oligodendrocytes in the next years. Here, we review recent advances in understanding the precise role of mentioned glial cell types in the main pathological events of ischemic stroke, including inflammation, blood brain barrier integrity, excitotoxicity, reactive oxygen species management, metabolic support, and neurogenesis, among others, with a special attention to tested therapeutic approaches.

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Section: Microgliamentioning

confidence: 99%

Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

Hernández

Villa-González

Martín

et al. 2021

Cells

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“…In the current study, we found rCCL17-mediated Tregs recruitment into peri-hematoma regions alleviated the early brain injury by promoting the M2 polarization of microglial/macrophages after ICH. In the early stages of ICH, microglia is the rst innate immune response cell among non-neuronal cells 7,35 .…”

Section: Discussionmentioning

confidence: 99%

Recruitment of regulatory T cells with rCCL17 promotes M2 microglia/macrophage polarization through TGFβ/TGFβR/Smad2/3 pathway in a mouse model of intracerebral hemorrhage

Deng

Jin

Liu

et al. 2023

Experimental Neurology

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“…Early studies showed that both mGlu5 receptor agonists and antagonists reduced infarct size in a rat intraluminal filament model of transient MCA occlusion (37), whereas pharmacological activation of mGlu5 receptors was not protective in the endothelin-1 rat model of focal ischemia (38). More recent findings showed that selective pharmacological blockade of mGlu5 receptors reduced microglial activation and neuronal death induced by acute intracerebral hemorrhage (39). The mGlu4 receptors are also potential drug targets for neuroprotection in ischemic stroke as shown by the evidence that mGlu4 receptor activation reduced infarct size in ischemic mice and rats, whereas brain damage was amplified in mGlu4 −/− mice (40).…”

Section: Discussionmentioning

confidence: 99%

Genetic Deletion of mGlu3 Metabotropic Glutamate Receptors Amplifies Ischemic Brain Damage and Associated Neuroinflammation in Mice

et al. 2021

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Backgroud: Type-3 metabotropic glutamate (mGlu3) receptors are found in both neurons and glial cells and regulate synaptic transmission, astrocyte function, and microglial reactivity. Here we show that the genetic deletion of mGlu3 receptors amplifies ischemic brain damage and associated neuroinflammation in adult mice. An increased infarct size was observed in mGlu3−/− mice of both CD1 and C57Black strains 24 h following a permanent occlusion of the middle cerebral artery (MCA) as compared to their respective wild-type (mGlu3+/+ mice) counterparts. Increases in the expression of selected pro-inflammatory genes including those encoding interleukin-1β, type-2 cycloxygenase, tumor necrosis factor-α, CD86, and interleukin-6 were more prominent in the peri-infarct region of mGlu3−/− mice. In contrast, the expression of two genes associated with the anti-inflammatory phenotype of microglia (those encoding the mannose-1-phosphate receptor and the α-subunit of interleukin-4 receptor) and the gene encoding the neuroprotective factor, glial cell line-derived neurotrophic factor, was enhanced in the peri-infarct region of wild-type mice, but not mGlu3−/− mice, following MCA occlusion. In C57Black mice, the genetic deletion of mGlu3 receptors worsened the defect in the paw placement test as assessed in the contralateral forepaw at short times (4 h) following MCA occlusion. These findings suggest that mGlu3 receptors are protective against ischemic brain damage and support the way to the use of selective mGlu3 receptor agonists or positive allosteric modulators in experimental animal models of ischemic stroke.

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Attenuation of Acute Intracerebral Hemorrhage-Induced Microglial Activation and Neuronal Death Mediated by the Blockade of Metabotropic Glutamate Receptor 5 In Vivo

Cited by 11 publications

References 62 publications

Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

Glial Cells as Therapeutic Approaches in Brain Ischemia-Reperfusion Injury

Recruitment of regulatory T cells with rCCL17 promotes M2 microglia/macrophage polarization through TGFβ/TGFβR/Smad2/3 pathway in a mouse model of intracerebral hemorrhage

Genetic Deletion of mGlu3 Metabotropic Glutamate Receptors Amplifies Ischemic Brain Damage and Associated Neuroinflammation in Mice

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