Evaluation of the Effectiveness of Post-Stroke Metformin Treatment Using Permanent Middle Cerebral Artery Occlusion in Rats.
Evaluation of the Effectiveness of Post-Stroke Metformin Treatment Using Permanent Middle Cerebral Artery Occlusion in Rats.
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DOI：
10.3390/ph14040312
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发表时间：
2021-04-01
期刊：
影响因子：
--
通讯作者：
Rastenyte D
中科院分区：
文献类型：
--
作者：
Zemgulyte G;Tanaka S;Hide I;Sakai N;Pampuscenko K;Borutaite V;Rastenyte D
中风是全球第二大死亡原因。缺血性卒中的治疗选择有限，开发新的治疗药物或联合治疗势在必行。越来越多的证据表明，二甲双胍治疗，由于其抗炎作用，对缺血/再灌注诱导的脑损伤发挥神经保护作用。实验评估通常在脑短暂缺血随后长期再灌注的模型中进行。本研究的目的是评估二甲双胍治疗对大鼠永久性大脑中动脉闭塞（pMCAO）无再灌注后的神经保护作用。使用Longa量表评估神经功能缺损，该量表提供了pMCAO后身体运动的分级量表。用氯化三苯基四氮唑染色测量梗死面积和脑水肿面积。通过免疫组织化学染色评价脑切片中神经元和总的和活化的小胶质细胞的数量以及白细胞介素10（IL-10）的产生。我们的研究结果表明，二甲双胍治疗改善神经系统状态，并减少梗死面积后120小时的pMCAO。在pMCAO 48小时后，二甲双胍还可防止缺血性皮质中的神经元损失，但不能防止纹状体中的神经元损失。此外，卒中后二甲双胍治疗显著降低了48 h时总的和活化的小胶质细胞数量。二甲双胍的抗炎作用与pMCAO后48小时IL-10产生增加相关。本研究的结果表明，中风后二甲双胍治疗在pMCAO模型中发挥抗炎和神经保护作用。
Stroke is the second leading cause of death worldwide. Treatment options for ischemic stroke are limited, and the development of new therapeutic agents or combined therapies is imperative. Growing evidence suggests that metformin treatment, due to its anti-inflammatory action, exerts a neuroprotective effect against ischemia/reperfusion-induced brain damage. Experimental assessment has typically been performed in models of cerebral transient ischemia followed by long-term reperfusion. The aim of this study was to evaluate the neuroprotective effect of metformin treatment after permanent middle cerebral artery occlusion (pMCAO) without reperfusion in rats. Neurological deficits were assessed using the Longa scale, which offers a graded scale on body movement following pMCAO. Both infarct size and brain oedema area were measured by staining with 2,3,5-triphenyltetrazolium chloride. The number of neurons and total and activated microglia, as well as interleukin 10 (IL-10) production, in brain sections were evaluated by immunohistochemical staining. Our results show that metformin treatment improves the neurological state and reduces infarct size after 120 h of pMCAO. Metformin also prevents neuronal loss in the ischemic cortex but not in the striatum after 48 h of pMCAO. Moreover, post-stroke treatment with metformin significantly decreases the number of total and activated microglia at 48 h. The anti-inflammatory effect of metformin is associated with increased IL-10 production at 48 h after pMCAO. The results of the present study suggest that post-stroke treatment with metformin exerts anti-inflammatory and neuroprotective effects in a pMCAO model.
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DOI：
10.2147/dddt.s56071
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Fluri F;Schuhmann MK;Kleinschnitz C
通讯作者：
Kleinschnitz C
DOI：
10.1038/jcbfm.2009.255
发表时间：
2010-03
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
通讯作者：
--
影响因子：
158.5
作者：
Hacke, Werner;Kaste, Markku;Toni, Danilo
通讯作者：
Toni, Danilo
DOI：
10.1016/j.jstrokecerebrovasdis.2015.10.016
发表时间：
2016-02-01
影响因子：
2.5
作者：
Mima, Yohei;Kuwashiro, Takahiro;Okada, Yasushi
通讯作者：
Okada, Yasushi
影响因子：
4.3
作者：
Kuts, Ruslan;Frank, Dmitry;Boyko, Matthew
通讯作者：
Boyko, Matthew