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Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury
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نویسنده
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byrnes k.r. ,loane d.j. ,stoica b.a. ,zhang j. ,faden a.i.
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منبع
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journal of neuroinflammation - 2012 - دوره : 9 - شماره : 0
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چکیده
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Background: traumatic brain injury initiates biochemical processes that lead to secondary neurodegeneration. imaging studies suggest that tissue loss may continue for months or years after traumatic brain injury in association with chronic microglial activation. recently we found that metabotropic glutamate receptor 5 (mglur5) activation by (rs)-2-chloro-5-hydroxyphenylglycine (chpg) decreases microglial activation and release of associated pro-inflammatory factors in vitro,which is mediated in part through inhibition of reduced nicotinamide adenine dinucleotide phosphate (nadph) oxidase. here we examined whether delayed chpg administration reduces chronic neuroinflammation and associated neurodegeneration after experimental traumatic brain injury in mice.methods: one month after controlled cortical impact traumatic brain injury,c57bl/6 mice were randomly assigned to treatment with single dose intracerebroventricular chpg,vehicle or chpg plus a selective mglur5 antagonist,3-((2-methyl-4-thiazolyl)ethynyl)pyridine. lesion volume,white matter tract integrity and neurological recovery were assessed over the following three months.results: traumatic brain injury resulted in mglur5 expression in reactive microglia of the cortex and hippocampus at one month post-injury. delayed chpg treatment reduced expression of reactive microglia expressing nadph oxidase subunits; decreased hippocampal neuronal loss; limited lesion progression,as measured by repeated t2-weighted magnetic resonance imaging (at one,two and three months) and white matter loss,as measured by high field ex vivo diffusion tensor imaging at four months; and significantly improved motor and cognitive recovery in comparison to the other treatment groups.conclusion: markedly delayed,single dose treatment with chpg significantly improves functional recovery and limits lesion progression after experimental traumatic brain injury,likely in part through actions at mglur5 receptors that modulate neuroinflammation. © 2012 byrnes et al; licensee biomed central ltd.
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کلیدواژه
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Delayed treatment; Metabotropic glutamate receptor 5; Microglia; Neuroprotection; Traumatic brain injury
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آدرس
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department of neuroscience,georgetown university medical center,washington,dc,united states,department of anatomy,physiology and genetics,uniformed services university of the health sciences,bethesda,md, United States, department of neuroscience,georgetown university medical center,washington,dc,united states,department of anesthesiology and center for shock,trauma and anesthesiology research (star),national study center for trauma and ems,university of maryland school of medicine,baltimore,md, United States, department of neuroscience,georgetown university medical center,washington,dc,united states,department of anesthesiology and center for shock,trauma and anesthesiology research (star),national study center for trauma and ems,university of maryland school of medicine,baltimore,md, United States, department of radiology,johns hopkins university,baltimore,md, United States, department of neuroscience,georgetown university medical center,washington,dc,united states,department of anesthesiology and center for shock,trauma and anesthesiology research (star),national study center for trauma and ems,university of maryland school of medicine,baltimore,md, United States
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Authors
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