Cocaine-and amphetamine-regulated transcript modulates peripheral immunity and protects against brain injury in experimental stroke
Cocaine-and amphetamine-regulated transcript modulates peripheral immunity and protects against brain injury in experimental stroke
复制标题
可卡因和安非他明调节的转录物调节外周免疫并防止实验性中风中的脑损伤
DOI：
10.1016/j.bbi.2010.09.017
复制
发表时间：
2011-02-01
影响因子：
15.1
通讯作者：
Xu, Yun
中科院分区：
文献类型：
--
作者：
Chang, Leilei;Chen, Yanting;Xu, Yun
缺血性卒中可诱导外周免疫系统的立即激活和随后的抑制，这可能导致更差的结果。可卡因和安非他明调节转录物（CART）肽已被报道在各种细胞和动物实验模型中分别具有神经保护和免疫调节作用。本研究探讨了CART在实验性脑卒中中的作用及其免疫调节机制。在雄性C57 BL/6小鼠中进行120分钟的大脑中动脉闭塞（MCAO），有或没有CART治疗或假手术，外周免疫指标和血清儿茶酚（CA）进行了分析。CART在24 h降低MCAO小鼠血中CD 4（+）/CD 8（+）比值和促炎细胞因子的表达，而在96 h上调MCAO小鼠脾中CD 4（+）/CD 8（+）比值和增强抗炎细胞因子的表达。此外，与对照小鼠相比，CART处理的小鼠在6和24 h时血清CA升高，而在96 h时血清CA和血液调节性T（Treg）细胞水平降低。同时测定小鼠脑细胞因子表达、脑梗死体积和神经功能缺损。CART减少了卒中后梗死体积，改善了神经功能，减少了受损大脑中炎症因子的表达。研究结果表明，CART在调节脑卒中后免疫反应中起重要作用，并在实验性脑卒中中发挥神经保护作用。研究结果还表明，CART在中风中的保护作用的可能机制是交感神经系统（SNS）通路的调节，因为CA，Treg细胞和白细胞介素（IL）-10是SNS的主要调节剂。(C)2010年爱思唯尔公司All rights reserved.
Ischemic stroke can induce immediate activation and later inhibition of the peripheral immune system which may contribute to a worse outcome. Cocaine-and amphetamine-regulated transcript (CART) peptides have been reported to have neuroprotective and immunomodulatory effects in various cell and animal experimental models, respectively. In this study, CART's role in experimental stroke and the relevant immune-regulating mechanisms was investigated. In male C57BL/6 mice subjected to 120 min of middle cerebral artery occlusion (MCAO), with or without CART treatment or sham operation, peripheral immune parameters and serum catecholamins (CAs) were analyzed. CART reduced blood CD4(+)/CD8(+) ratio and pro-inflammatory cytokine expression in MCAO mice at 24 h, while upregulated spleen CD4(+)/CD8(+) ratio and enhanced anti-inflammatory cytokines expressions in MCAO mice at 96 h. In addition, in comparison to control mice, CART-treated mice demonstrated elevated serum CAs at 6 and 24 h, whereas reduced serum levels of CAs and blood regulatory T (Treg) cells at 96 h. The cytokine expression, infarct volume and neurological deficits in mouse brain were also measured. CART reduced post-stroke infarct volume and improved neurological functions, with reduced expression of inflammatory factors in the injured brain. Findings indicate that CART plays an important role in modulating post-stroke immune response and exerts a neuroprotective effect in experimental stroke. Findings also suggest that the possible mechanism of CARTs protective action in stroke is the regulation of the sympathetic nervous system (SNS) pathway since CAs, Treg cells and interleukin (IL)-10 are the major modulators of SNS. (C) 2010 Elsevier Inc. All rights reserved.