Allopurinol protects against ischemic insults in a mouse model of cortical microinfarction

Allopurinol protects against ischemic insults in a mouse model of cortical microinfarction
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别嘌呤醇可预防皮质微梗塞小鼠模型的缺血性损伤

DOI:
10.1016/j.brainres.2015.07.010
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发表时间:
2015-10
期刊:
影响因子:
2.9
通讯作者:
Pei Zhong
Pei Zhong
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Qun;Lan Yue;He Xiao-fei;Luo Chuan-ming;Wang Qin-mei;Liang Feng-yin;Xu Guang-qing;Pei Zhong

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微梗死在认知能力下降和痴呆患者中很常见。别嘌呤醇(ALLO)是一种黄嘌呤氧化酶(XO)抑制剂,已发现可减少血管系统中的促炎分子和氧化应激。我们在此研究了别嘌呤醇预处理对皮质微梗死的影响。C57 BL/6 J小鼠经受由双光子激光照射诱导的永久性单穿透性小动脉闭塞。采用免疫组化法检测缺血脑梗死体积、胶质细胞活化和亚硝化应激。ALLO预处理可使梗死体积减少42%,并显著减少缺血脑中的小胶质细胞浸润、星形胶质细胞增殖和亚硝化应激。这些数据表明,ALLO可能通过抑制亚硝化应激和衰减小胶质细胞浸润以及星形胶质细胞再活化来防止微梗死。
Microinfarcts are common in patients with cognitive decline and dementia. Allopurinol (ALLO), a xanthine oxidase (XO) enzyme inhibitor, has been found to reduce proinflammatory molecules and oxidative stress in the vasculature. We here examined the effect of pre-treatment with allopurinol on the cortical microinfarction. C57BL/6J mice were subjected to a permanent single penetrating arteriole occlusion induced by two-photon laser irradiation. Infarction volume, the activation of glial cells and nitrosative stress in the ischemic brain was assessed using immunohistochemistry. Pre-treatment with ALLO achieved 42% reduction of infarct volume and significantly reduced microglia infiltration, astrocyte proliferation and nitrosative stress in the ischemic brain. These data indicate that ALLO protects against microinfarcts possibly through inhibition of nitrosative stress and attenuation of microglia infiltration as well as astrocytes reactivation.
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