Department of Emergency, Shanxi Provincial People's Hospital, Taiyuan 030001, China.
Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Histology and Embryology, School of Basic Medical Sciences, Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100069, China.
Biomed Pharmacother. 2024 Oct;179:117337. doi: 10.1016/j.biopha.2024.117337. Epub 2024 Aug 27.
Increased blood-brain barrier (BBB) permeability can lead to cerebral vasogenic edema and hemorrhagic transformation (HT) after reperfusion with tissue plasminogen activator (tPA), the only United States Food and Drug Administration (FDA)-approved treatment for acute ischemia stroke (AIS). The therapeutic benefits of tPA after AIS are partially outweighed by a more than a six-fold increase in the risk of symptomatic intracerebral hemorrhage. Therefore, strategies to protect the integrity of BBB are urgently needed to reduce HT and vasogenic edema after tPA thrombolysis or endovascular thrombectomy. Interestingly, an NIH study showed that smokers treated with tPA had a significantly lower prevalence of brain hemorrhage than nonsmokers, suggesting that cigarette smoking may protect patients treated with tPA from the side effects of cerebral hemorrhage. Importantly, we recently showed that treatment with nicotine reduces AIS-induced BBB damage and that modulating α7nAChR by modulation could reduce ischemia/reperfusion-induced BBB damage, suggesting that α7nAChR could be a potential target to reduce BBB after AIS. In this review, we first provide an overview of stroke and the impact of α7nAChR activation on BBB damage. Next, we discuss the features and mechanism of BBB destruction after AIS. We then discuss the effect of nicotine effect on BBB integrity as well as the mechanism underlying those effects. Finally, we discuss the side effects and potential strategies for modulating α7nAChR to reduce AIS-induced BBB damage.
血脑屏障（BBB）通透性增加可导致组织型纤溶酶原激活剂（tPA）再灌注后发生血管源性脑水肿和出血性转化（HT），tPA 是唯一获得美国食品和药物管理局（FDA）批准用于治疗急性缺血性脑卒中（AIS）的药物。尽管 tPA 治疗 AIS 具有一定的益处，但与 HT 和血管源性脑水肿相关的风险增加了六倍以上。因此，迫切需要保护 BBB 的完整性，以减少 tPA 溶栓或血管内取栓后 HT 和血管源性脑水肿的发生。有趣的是，一项 NIH 研究表明，接受 tPA 治疗的吸烟者发生脑出血的比例明显低于不吸烟者，这表明吸烟可能使接受 tPA 治疗的患者免受脑出血的副作用影响。重要的是，我们最近发现，尼古丁治疗可减轻 AIS 引起的 BBB 损伤，而通过调节α7nAChR 可减少缺血/再灌注引起的 BBB 损伤，这表明α7nAChR 可能是减少 AIS 后 BBB 损伤的潜在靶点。在这篇综述中，我们首先概述了脑卒中以及α7nAChR 激活对 BBB 损伤的影响。接下来，我们讨论了 AIS 后 BBB 破坏的特征和机制。然后，我们讨论了尼古丁对 BBB 完整性的影响及其作用机制。最后，我们讨论了调节α7nAChR 以减少 AIS 引起的 BBB 损伤的副作用和潜在策略。
