Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, No. 222 South Tianshui Road, Lanzhou, Gansu Province, 730000, China.
J Neuroimmune Pharmacol. 2024 Aug 14;19(1):43. doi: 10.1007/s11481-024-10146-6.
Recent studies have demonstrated the interaction between gut microbiota and brain on ischemic stroke, but the roles of gut microbiota in the pathophysiology of ischemic stroke remain largely unclear. In this study, we detected a significant increase of intestinal Akkermansia muciniphila (AKK) following ischemic stroke by a rose bengal photothrombosis model. To investigate the function and mechanism of AKK on ischemic stroke, we performed the AKK administration prior to stroke surgery. The results showed that mice treated with AKK gained significantly higher body weight and behaved better than those in PBS group at 3 days after ischemic stroke. Consistently, AKK administration remarkably decreased the infarct volumes as well as the density of degenerating neurons and apoptotic cells after ischemic stroke. Notably, AKK is a potential therapeutic target in immune-related disorders connected to the microbiota, and inflammation is crucially involved in the pathophysiological process of ischemic stroke. For the determination of underlying mechanisms of this protective effect, we investigated whether there are associations between AKK and neuroinflammation following ischemic stroke. The results suggested that AKK administration significantly reduced the activation of astrocytes and microglia but up-regulated multiple anti-inflammatory factors following ischemic stroke. Therefore, our study highlighted the beneficial roles of intestinal AKK on ischemic stroke and provided a new perspective for the treatment of ischemic stroke.
最近的研究表明，肠道微生物群与脑在缺血性卒中之间存在相互作用，但肠道微生物群在缺血性卒中病理生理学中的作用在很大程度上仍不清楚。在这项研究中，我们通过玫瑰红血卟啉光血栓形成模型发现，缺血性卒中后肠道阿克曼氏菌（Akkermansia muciniphila，AKK）明显增加。为了研究 AKK 对缺血性卒中的作用和机制，我们在卒中手术前进行了 AKK 给药。结果表明，与 PBS 组相比，缺血性卒中后 3 天，接受 AKK 治疗的小鼠体重明显增加，行为表现更好。一致地，AKK 给药显著减少了缺血性卒中后的梗死体积以及变性神经元和凋亡细胞的密度。值得注意的是，AKK 是与微生物群相关的免疫相关疾病的潜在治疗靶点，炎症在缺血性卒中的病理生理过程中起着至关重要的作用。为了确定这种保护作用的潜在机制，我们研究了 AKK 与缺血性卒中后神经炎症之间是否存在关联。结果表明，AKK 给药显著减少了缺血性卒中后星形胶质细胞和小胶质细胞的激活，但上调了多种抗炎因子。因此，我们的研究强调了肠道 AKK 对缺血性卒中的有益作用，并为缺血性卒中的治疗提供了新的视角。
