Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury.
Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury.
复制标题
延迟的MGLUR5激活限制了创伤性脑损伤后神经炎症和神经退行性的限制。
DOI：
10.1186/1742-2094-9-43
复制
发表时间：
2012-02-28
影响因子：
9.3
通讯作者：
Faden AI
中科院分区：
文献类型：
--
作者：
Byrnes KR;Loane DJ;Stoica BA;Zhang J;Faden AI
创伤性脑损伤会启动生化过程，导致继发性神经变性。影像研究表明，创伤性脑损伤后的组织丢失可能会持续数月或数年，并与慢性小胶质细胞激活有关。最近我们发现，在体外，(RS)-2-氯-5-羟基苯甘氨酸(CHPG)激活代谢型谷氨酸受体5(MGluR5)可减少小胶质细胞的激活和相关促炎因子的释放，这一作用部分是通过抑制还原的NADPH氧化酶来实现的。在这里，我们研究了延迟给予CHPG是否减少了小鼠实验性创伤性脑损伤后的慢性神经炎症和相关的神经变性。C57BL/6小鼠在控制性皮质冲击性脑损伤后1个月，随机分为3组，分别给予单次脑室内注射CHPG、赋形剂或CHPG加选择性mGluR5拮抗剂3-((2-甲基-4-噻唑基)乙炔)吡啶。在接下来的三个月中评估病变体积、白质束完整性和神经恢复情况。脑创伤后1个月，大脑皮质和海马区反应性小胶质细胞表达mGluR5。延迟的CHPG治疗减少了表达NADPH氧化酶亚单位的反应性小胶质细胞的表达；减少了海马神经元的丢失；通过重复T2加权磁共振成像(在1个月、2个月和3个月)和脑白质丢失(根据高场体外扩散张量成像)在4个月时测量了有限的病变进展；与其他治疗组相比，显著改善了运动和认知的恢复。明显延迟的CHPG单剂量治疗显著改善了实验性创伤性脑损伤后的功能恢复并限制了损伤的进展，这可能部分是通过对调节神经炎症的mGluR5受体的作用而实现的。
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. 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. 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. 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.
登录
查看更多内容
影响因子：
2.2
作者：
Gentleman, SM;Leclercq, PD;Nicoll, JAR
通讯作者：
Nicoll, JAR
DOI：
10.1006/jmrb.1994.1037
发表时间：
1994-03-01
期刊：
JOURNAL OF MAGNETIC RESONANCE SERIES B
影响因子：
--
作者：
BASSER, PJ;MATTIELLO, J;LEBIHAN, D
通讯作者：
LEBIHAN, D
DOI：
10.1016/j.nurt.2008.10.038
发表时间：
2009-01
期刊：
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
影响因子：
--
作者：
Byrnes KR;Loane DJ;Faden AI
通讯作者：
Faden AI
影响因子：
3.3
作者：
Aggarwal, Manisha;Mori, Susumu;Shimogori, Tomomi;Blackshaw, Seth;Zhang, Jiangyang
通讯作者：
Zhang, Jiangyang
影响因子：
16.8
作者：
Gao HM;Hong JS
通讯作者：
Hong JS