Offsetting the impact of smoking and e-cigarette vaping on the cerebrovascular system and stroke injury: Is Metformin a viable countermeasure?
Offsetting the impact of smoking and e-cigarette vaping on the cerebrovascular system and stroke injury: Is Metformin a viable countermeasure?
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DOI：
10.1016/j.redox.2017.06.006
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发表时间：
2017-10
期刊：
影响因子：
11.4
通讯作者：
Cucullo L
中科院分区：
文献类型：
--
作者：
Kaisar MA;Villalba H;Prasad S;Liles T;Sifat AE;Sajja RK;Abbruscato TJ;Cucullo L
最近发表的体外和体内研究结果强烈表明，烟草烟雾（TS）导致的BBB损伤和卒中风险增加与2型糖尿病（2DM）非常相似，并且在很大程度上响应于常见的关键调节剂，如氧化应激（OS），炎症和由核因子红细胞2相关因子（Nrf 2）调节的内源性抗氧化反应系统（ARE）的改变。临床前研究还表明，尼古丁（电子烟中使用的主要电子烟液成分）也会导致OS、脑缺血加重和继发性脑损伤。在本文中，我们提供的证据表明，与TS类似，长期电子烟（e-Cig）vaping可能是血脑屏障（BBB）完整性丧失和血管炎症的前兆，也是中风发作和缺血后脑损伤恶化的促进因素。此外，最近的报道表明，在缺血性损伤之前和之后的Metalloy（MF）治疗降低了应激并抑制了炎症反应。我们小组最近发表的数据显示，MF促进了由Nrf 2激活介导的对抗机制的激活，这大大降低了TS在脑和脑血管水平的毒性，并保护了BBB的完整性。在这项研究中，我们提供了额外的体内证据，表明MF可以有效降低中风的氧化和炎症风险，并减轻TS和电子烟vaping促进的缺血后脑损伤。我们的数据还表明，在戒烟后中风风险水平重新正常化所需的时间窗内，MF给药可以作为预防性护理延长，因此该方向的进一步研究是值得的。慢性香烟和电子烟暴露下调血栓调节蛋白和Nrf 2。慢性CS和电子烟暴露使经历tMCAO的小鼠的中风结果恶化。二甲双胍改善CS和e-Cig暴露小鼠经历tMCAO的中风结果。MF的保护作用与Nrf 2水平的重正化相关。
Recently published in vitro and in vivo findings strongly suggest that BBB impairment and increased risk for stroke by tobacco smoke (TS) closely resemble that of type-2 diabetes (2DM) and develop largely in response to common key modulators such oxidative stress (OS), inflammation and alterations of the endogenous antioxidative response system (ARE) regulated by the nuclear factor erythroid 2-related factor (Nrf2). Preclinical studies have also shown that nicotine (the principal e-liquid's ingredient used in e-cigarettes) can also cause OS, exacerbation of cerebral ischemia and secondary brain injury. Herein we provide evidence that likewise to TS, chronic e-Cigarette (e-Cig) vaping can be prodromal to the loss of blood-brain barrier (BBB) integrity and vascular inflammation as well as act as a promoting factor for the onset of stroke and worsening of post-ischemic brain injury. In addition, recent reports have shown that Metformin (MF) treatment before and after ischemic injury reduces stress and inhibits inflammatory responses. Recent published data by our group revealead that MF promotes the activation of counteractive mechanisms mediated by the activation of Nrf2 which drastically reduce TS toxicity at the brain and cerebrovascular levels and protect BBB integrity. In this study we provide additional in vivo evidence showing that MF can effectively reduce the oxidative and inflammatory risk for stroke and attenuate post-ischemic brain injury promoted by TS and e-Cig vaping. Our data also suggest that MF administration could be extended as prophylactic care during the time window required for the renormalization of the risk levels of stroke following smoking cessation thus further studies in that direction are warrated. Chronic cigarette and e-cigarette exposure downregulate throbomodulin and Nrf2. Chronic CS and e-Cig exposure worsen stroke outcome in mice undergoing tMCAO. Metformin ameliorate stroke outcomes in CS and e-Cig exposed mice undergoing tMCAO. MF protective effect correlates with renormalization of Nrf2 levels.