Regional sensitivity to neuroinflammation: in vivo and in vitro studies.
Regional sensitivity to neuroinflammation: in vivo and in vitro studies.
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DOI：
10.1002/syn.20889
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发表时间：
2011-07
期刊：
影响因子：
2.3
通讯作者：
Biegon, Anat
中科院分区：
文献类型：
--
作者：
Liraz-Zaltsman, Sigal;Alexandrovich, Alexander G.;Trembovler, Victoria;Fishbein, Ianai;Yaka, Rami;Shohami, Esther;Biegon, Anat
关键词：
神经炎症涉及几种急性发作的神经病理学，例如脑膜炎、脑炎、中风和创伤性脑损伤以及神经退行性疾病。所有这些病理都与认知缺陷有关。使用纯神经炎症模型（在小鼠脑池内注射内毒素），我们测试的假设，参与认知的大脑区域是最容易受到炎症损伤，这种脆弱性是新皮层神经元的固有属性。在枕大池中注射内毒素（LPS）或生理盐水的小鼠（N=10/组）进行神经行为和认知测试，然后用[3 H] PK 11195（一种确定的小胶质细胞增生标志物）进行定量放射自显影评估局部神经炎症。平行地，将取自胚胎第19天大鼠胚胎或出生后第1天表达绿色荧光蛋白的小鼠的皮质和纹状体神经元的共培养物暴露于促炎细胞因子TNF α、谷氨酸或两种试剂的组合24小时。LPS处理的小鼠表现出显着的记忆缺陷和显着增加的特定PK 11195结合在皮质和海马区，但不是在纹状体。培养的皮质神经元显示出显着较低的存活率相对于纹状体神经元在响应TNF α，谷氨酸或两种药剂的组合。此外，TNF α发挥神经保护作用，而不是神经毒性作用的纹状体，但不是在皮层神经元。这些结果表明，皮质本质上比纹状体更敏感的神经炎症的有害影响，并可能提供一个解释的优势，认知功能障碍的神经病理与神经炎症的组成部分。
Neuroinflammation is involved in several acute-onset neuropathologies such as meningitis, encephalitis, stroke and traumatic brain injury as well as in neurodegenerative diseases. All of these patholologies are associated with cognitive deficits. Using a model of pure neuroinflammation (intracisternal injection of endotoxin in mice), we tested the hypothesis that brain regions involved in cognition are the most vulnerable to inflammatory insults, and this vulnerability is an inherent property of neocortical neurons. Mice (N=10/group) injected with endotoxin (LPS) or saline in the cisterna magna underwent neurobehavioral and cognitive testing followed by quantitative autoradiographic assessment of regional neuroinflammation with [3H]PK11195, an established marker of microgliosis. In parallel, co-cultures of cortical and striatal neurons taken from embryonic day 19 rat embryos or postnatal day 1 mice expressing green fluorescent protein were exposed for 24 h to the proinflammatory cytokine TNFalpha, glutamate or a combination of the two agents. LPS treated mice exhibited significant deficits in memory and significant increases in specific PK11195 binding in cortical and hippocampal regions, but not in striatum. Cultured neurons of cortical origin showed significantly lower survival rate relative to striatal neurons in response to TNFalpha, glutamate or a combination of the two agents. Furthermore, TNFalpha exerted neuroprotective rather than neurotoxic effects in the striatal but not in the cortical neurons. These results suggest that the cortex is inherently more sensitive than the striatum to the deleterious effects of neuroinflammation, and may offer an explanation for the preponderance of cognitive deficits in neuropathologies with a neuroinflammatory component.
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