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

Neurochemical Research
Md Saidur RahmanYong Liu

Abstract

The activation of microglia in response to intracerebral hemorrhagic stroke is one of the principal components of the progression of this disease. It results in the formation of pro-inflammatory cytokines that lead to neuronal death, a structural deterioration that, in turn interferes with functional recovery. Metabotropic glutamate receptor 5 (mGluR5) is highly expressed in reactive microglia and is involved in the pathological processes of brain disorders, but its role in intracerebral hemorrhage (ICH) remains unknown. We hypothesized that mGluR5 regulates microglial activation and ICH maintenance. In this study, collagenase-induced ICH mice received a single intraperitoneal injection of the mGluR5 antagonist-, MTEP, or vehicle 2 h after injury. We found that acute ICH upregulated mGluR5 and microglial activation. mGluR5 was highly localized in reactive microglia in the peri-hematomal cortex and striatum on days 3 and 7 post-ICH. The MTEP-mediated pharmacological inhibition of mGluR5 in vivo resulted in the substantial attenuation of acute microglial activation and IL-6, and TNF-α release. We also showed that the blockade of mGluR5 markedly reduced cell apoptosis, and neurodegeneration and markedly elevated neuroprotection. F...Continue Reading

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Methods Mentioned

BETA
fluorescence microscopy
ELISA
protein assay
X-ray

Software Mentioned

ImageJ
GraphPad Prism
SigmaStat
Systat
SPSS

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