Delayed postconditioning protects against focal ischemic brain injury in rats.
Delayed postconditioning protects against focal ischemic brain injury in rats.
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DOI：
10.1371/journal.pone.0003851
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发表时间：
2008
期刊：
影响因子：
3.7
通讯作者：
Zhao, Heng
中科院分区：
文献类型：
--
作者：
Ren, Chuancheng;Gao, Xuwen;Niu, Gang;Yan, Zhimin;Chen, Xiaoyuan;Zhao, Heng
我们和其他人已经报道了快速缺血后处理，中断中风后早期再灌注，减少大鼠梗死。然而，其极短的治疗时间窗，从再灌注后几秒钟到几分钟，可能会阻碍其临床转化。因此，在这项研究中，我们探讨了延迟后处理，这是再灌注后几个小时进行，提供保护，防止中风。局灶性缺血产生的30分钟闭塞双侧颈总动脉（CCA）结合永久闭塞大脑中动脉（MCA）;延迟后处理进行重复，短暂的闭塞和释放的双边CCA，或单独的同侧CCA。结果，在中风后3小时和6小时进行的延迟后处理有力地减少了梗死面积，从6小时开始进行的6个周期的15分钟闭塞/15分钟释放同侧CCA的延迟后处理实现了最强的保护。我们发现，这种延迟的后处理通过减少梗死和改善行为测试的结果提供了长达两个月的长期保护;它还减弱了2-[18 F]-氟-2-脱氧-D-葡萄糖（FDG）摄取的减少，从而改善了代谢，并减少了水肿和血脑屏障渗漏。组织型纤溶酶原激活剂（tPA）的应用可使缺血性脑卒中患者获得再灌注，但tPA的副作用可加重缺血性脑损伤。因此，我们测试是否延迟后处理抵消t-PA的加重作用。结果表明，延迟后处理减轻了t-PA对梗死的加重作用。延迟后处理减轻了脑缺血后的缺血性损伤，为脑卒中的治疗及其保护机制开辟了新的研究途径。
We and others have reported that rapid ischemic postconditioning, interrupting early reperfusion after stroke, reduces infarction in rats. However, its extremely short therapeutic time windows, from a few seconds to minutes after reperfusion, may hinder its clinical translation. Thus, in this study we explored if delayed postconditioning, which is conducted a few hours after reperfusion, offers protection against stroke. Focal ischemia was generated by 30 min occlusion of bilateral common carotid artery (CCA) combined with permanent occlusion of middle cerebral artery (MCA); delayed postconditioning was performed by repetitive, brief occlusion and release of the bilateral CCAs, or of the ipsilateral CCA alone. As a result, delayed postconditioning performed at 3h and 6h after stroke robustly reduced infarct size, with the strongest protection achieved by delayed postconditioning with 6 cycles of 15 min occlusion/15 min release of the ipsilateral CCA executed from 6h. We found that this delayed postconditioning provided long-term protection for up to two months by reducing infarction and improving outcomes of the behavioral tests; it also attenuated reduction in 2-[18F]-fluoro-2-deoxy-D-glucose (FDG)-uptake therefore improving metabolism, and reduced edema and blood brain barrier leakage. Reperfusion in ischemic stroke patients is usually achieved by tissue plasminogen activator (tPA) application, however, t-PA's side effect may worsen ischemic injury. Thus, we tested whether delayed postconditioning counteracts the exacerbating effect of t-PA. The results showed that delayed postconditioning mitigated the worsening effect of t-PA on infarction. Delayed postconditioning reduced ischemic injury after focal ischemia, which opens a new research avenue for stroke therapy and its underlying protective mechanisms.
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影响因子：
4
作者：
Burda, Jozef;Danielisova, Viera;Burda, Rastislav
通讯作者：
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影响因子：
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