Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice
Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice
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DOI：
10.1038/jcbfm.2009.257
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发表时间：
2010-04-01
影响因子：
6.3
通讯作者：
Fujiwara, Michihiro
中科院分区：
文献类型：
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作者：
Hayakawa, Kazuhide;Nakano, Takafumi;Fujiwara, Michihiro
神经胶质瘢痕形成传统上被认为是有害的中风后。但现在新的研究表明，反应性星形胶质细胞也可能有助于神经血管重塑。在这里，我们评估了在中风恢复的小鼠模型中反应性星形胶质细胞的代谢抑制的作用和机制。中风发作后5天，星形胶质细胞代谢抑制与氟柠檬酸（FC，1 nmol）。从1天到14天，对反应性星形胶质细胞标志物（胶质细胞酸性蛋白（GFAP），HMGB 1），神经血管重塑标志物（CD 31，突触素，PSD 95）和行为结果（神经评分，旋转棒潜伏期）进行定量。正如预期的那样，局灶性脑缺血在小鼠中诱导了显著的神经功能缺损。但在中风发作后的14天内，随着小鼠自发恢复，观察到神经评分和旋转棒疲劳的稳定改善。脑缺血后1 ~ 14天，梗死周围皮质共表达GFAP和HMGB 1的反应性星形胶质细胞增加，同时神经血管重塑标志物CD 31、突触素和PSD 95也增加。与仅中风对照组相比，FC治疗的小鼠表现出HMGB 1阳性反应性星形胶质细胞和神经血管重塑的显著减少，以及相应的行为恢复恶化。我们的研究结果表明，在梗死周围皮层的反应性星形胶质细胞可能会促进神经血管重塑，这些胶质细胞的反应可能有助于中风后的功能恢复。Journal of Cerebral Blood Flow & Metabolism（2010）30，871-882; doi：10.1038/jcbfm.2009.257; 2009年12月9日在线发表
Glial scarring is traditionally thought to be detrimental after stroke. But emerging studies now suggest that reactive astrocytes may also contribute to neurovascular remodeling. Here, we assessed the effects and mechanisms of metabolic inhibition of reactive astrocytes in a mouse model of stroke recovery. Five days after stroke onset, astrocytes were metabolically inhibited with fluorocitrate (FC, 1 nmol). Markers of reactive astrocytes (glial fibrillary acidic protein (GFAP), HMGB1), markers of neurovascular remodeling (CD31, synaptophysin, PSD95), and behavioral outcomes (neuroscore, rotarod latency) were quantified from 1 to 14 days. As expected, focal cerebral ischemia induced significant neurological deficits in mice. But over the course of 14 days after stroke onset, a steady improvement in neuroscore and rotarod latencies were observed as the mice spontaneously recovered. Reactive astrocytes coexpressing GFAP and HMGB1 increased in peri-infarct cortex from 1 to 14 days after cerebral ischemia in parallel with an increase in the neurovascular remodeling markers CD31, synaptophysin, and PSD95. Compared with stroke-only controls, FC-treated mice demonstrated a significant decrease in HMGB1-positive reactive astrocytes and neurovascular remodeling, as well as a corresponding worsening of behavioral recovery. Our results suggest that reactive astrocytes in peri-infarct cortex may promote neurovascular remodeling, and these glial responses may aid functional recovery after stroke. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 871-882; doi:10.1038/jcbfm.2009.257; published online 9 December 2009