Minocycline promotes axonal regeneration through suppression of RGMa in rat MCAO/reperfusion model
Minocycline promotes axonal regeneration through suppression of RGMa in rat MCAO/reperfusion model
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DOI：
10.1002/syn.21629
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发表时间：
2013-04-01
期刊：
影响因子：
2.3
通讯作者：
Qin, Xinyue
中科院分区：
文献类型：
--
作者：
Tao, Tao;Xu, Guanghui;Qin, Xinyue
米诺环素最近已被牵连在局灶性脑缺血再灌注（I/R）的保护作用，但对神经行为异常的保护作用仍然是矛盾的。在本研究中，我们探讨米诺环素是否改善轴突再生和神经功能的恢复，通过抑制排斥导向分子A（RGMa）的表达局灶性脑缺血再灌注后。将雄性SD大鼠右侧大脑中动脉（MCAO）闭塞2 h，再灌注后立即静脉注射米诺环素3 mg/kg，每日2次，共14 d。在预期时间点进行阶梯试验和改良神经系统严重程度评分（mNSS）以评价功能结局，并通过伊文思蓝染料外渗（EB）评估血脑屏障（BBB）通透性。MCAO后2周采用免疫组化和Western blot方法检测缺血区皮质RGMa的表达。神经丝蛋白200（NF-200）免疫组织化学染色用于评估轴突损伤。与I/R组相比，尾静脉注射米诺环素3 mg/kg显著减少EB外渗，升高mNSS，改善前肢运动功能（P < 0.05）。米诺环素治疗组轴突再生较I/R组明显增强（P < 0.05）。此外，米诺环素显着降低RGMa蛋白的表达MCAO后2周，如通过免疫染色和Western印迹评估。我们的研究表明，早期米诺环素治疗促进大鼠MCAO后神经功能恢复和轴突再生，这可能是通过下调RGMa表达介导的。Synapse，2013年。(c)2012 Wiley Periodicals，Inc.
Minocycline has been recently implicated in protection against focal cerebral ischemia reperfusion (I/R), but the protective effects on neurobehavioral abnormalities remains contradictory. In the present study, we investigate whether minocycline improves axonal regeneration and neurological function recovery by inhibiting the expression of the repulsive guidance molecular A (RGMa) after focal cerebral ischemia reperfusion. Male Sprague-Dawley (SD) rats were subjected to occlusion of the right middle cerebral artery (MCAO) for 2 h and 3 mg kg1 minocycline was injected intravenously immediately after reperfusion twice a day for 14 days. The staircase test and modified neurological severity score (mNSS) were performed to evaluate functional outcome and blood-brain barrier (BBB) permeability was assessed by Evan's blue dye extravasation (EB) at the expected time point. The expression of RGMa in ischemic cortex was measured by immunohistochemical staining and Western blot 2 weeks after MCAO. Neurofilament protein 200 (NF-200) immunohistochemical staining was used to assess axonal damage. Treatment with minocycline at a dose of 3 mg kg1 via the caudal vein significantly reduced the extravasation of EB, elevated mNSS and improved forelimb motor function as assessed by the staircase test when compared to the I/R group (P < 0.05). Moreover, axonal regrowth was enhanced in the minocycline treatment group when compared to the I/R group (P < 0.05). In addition, minocycline significantly reduced the expression of RGMa protein 2 weeks after MCAO as assessed by both immunostaining and Western blot. Our studies suggest that early minocycline treatment promotes neurological functional recovery and axonal regeneration in rats after MCAO, which might be mediated by down-regulating RGMa expression. Synapse, 2013. (c) 2012 Wiley Periodicals, Inc.