Remote ischemic postconditioning: harnessing endogenous protection in a murine model of vascular cognitive impairment.
Remote ischemic postconditioning: harnessing endogenous protection in a murine model of vascular cognitive impairment.
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DOI：
10.1007/s12975-014-0374-6
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发表时间：
2015-02
影响因子：
6.9
通讯作者：
Hess, David C.
中科院分区：
文献类型：
--
作者：
Khan, Mohammad Badruzzaman;Hoda, Md Nasrul;Vaibhav, Kumar;Giri, Shailendra;Wang, Philip;Waller, Jennifer L.;Ergul, Adviye;Dhandapani, Krishnan M.;Fagan, Susan C.;Hess, David C.
关键词：
我们以前曾报道过急性卒中时肢体缺血性条件反射（RLIC; PERconditioning）可产生神经保护作用，这可能是由于脑血流量（CBF）增加。血管性认知障碍（VCI）是一个日益严重的威胁，公共卫生没有任何已知的治疗。双侧颈总动脉狭窄（BCAS）小鼠模型被认为是最有效的VCI模型。我们假设RLIC（后处理; RIPostC）将在慢性脑灌注不足（CCH）期间增加CBF，并预防BCAS模型中的认知障碍。在C57/B6雄性小鼠中使用定制的微弹簧圈进行BCAS以建立CCH。在BCAS手术后一周，用RIPostC疗法每天一次治疗小鼠，持续2周。采用激光散斑对比成像仪测定不同时间点的脑血流。在BCAS后4周进行认知测试，并收获脑组织用于生物化学。BCAS导致慢性灌注不足，导致认知功能受损，如通过新物体识别（NOR）测试的。组织学检查显示，BCAS引发炎症反应，并导致频繁的空泡化和细胞死亡。BCAS还增加淀粉样β蛋白（Aβ）的产生和积累，导致白色物质（WM）和髓鞘碱性蛋白（MBP）的丢失。RIPostC治疗显示，即使在停止治疗一周后，CBF也出现了急性增加和持续改善。RIPostC可改善认知功能，抑制炎症反应，防止细胞死亡，减少Aβ的生成和蓄积，保护WM的完整性。RIPostC在BCAS模型中是有效的，可能是一种有吸引力的低成本常规治疗老年VCI患者的方法。RIPostC改善CBF和减轻组织损伤的机制需要在未来进行研究。本文的在线版本（doi：10.1007/s12975-014-0374-6）包含补充材料，可供授权用户使用。
We previously reported that remote limb ischemic conditioning (RLIC; PERconditioning) during acute stroke confers neuroprotection, possibly due to increased cerebral blood flow (CBF). Vascular cognitive impairment (VCI) is a growing threat to public health without any known treatment. The bilateral common carotid artery stenosis (BCAS) mouse model is regarded as the most valid model for VCI. We hypothesized that RLIC (postconditioning; RIPostC) will augment CBF during chronic cerebral hypoperfusion (CCH) and prevent cognitive impairment in the BCAS model. BCAS using customized microcoil was performed in C57/B6 male mice to establish CCH. A week after the BCAS surgery, mice were treated with RIPostC-therapy once daily for 2 weeks. CBF was measured with laser speckle contrast imager at different time points. Cognitive testing was performed at 4-week post-BCAS, and brain tissue was harvested for biochemistry. BCAS led to chronic hypoperfusion resulting into impaired cognitive function as tested by novel object recognition (NOR). Histological examinations revealed that BCAS triggered inflammatory responses and caused frequent vacuolization and cell death. BCAS also increased the generation and accumulation of amyloid beta protein (Aβ), resulting into the loss of white matter (WM) and myelin basic protein (MBP). RIPostC-therapy showed both acute increase as well as sustained improvement in CBF even after the cessation of therapy for a week. RIPostC improved cognitive function, inhibited inflammatory responses, prevented the cell death, reduced the generation and accumulation of Aβ, and protected WM integrity. RIPostC is effective in the BCAS model and could be an attractive low-cost conventional therapy for aged individuals with VCI. The mechanisms by which RIPostC improves CBF and attenuates tissue damage need to be investigated in the future. The online version of this article (doi:10.1007/s12975-014-0374-6) contains supplementary material, which is available to authorized users.
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