Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
J Mol Neurosci. 2022 Mar;72(3):642-652. doi: 10.1007/s12031-021-01917-4. Epub 2021 Oct 1.
Post-stroke disabilities like cognitive impairment impose are complex conditions with great economic burdens on health care systems. For these comorbidities, no effective therapies have been identified yet. Nicotinic acetylcholine receptors (nAChRs) are multifunctional receptors participating in various behavioral and neurobiological functions. During brain ischemia, the increased glutamate accumulation leads to neuronal excitotoxicity as well as mitochondrial dysfunction. These abnormalities then cause the increased levels of oxidants, which play key roles in neuronal death and apoptosis in the infarct zone. Additionally, recall of cytokines and inflammatory factors play a prominent role in the exacerbation of ischemic injury. As well, neurotrophic factors' insufficiency results in synaptic dysfunction and cognitive impairments in ischemic brain. Of note, nAChRs through various signaling pathways can participate in therapeutic approaches such as cholinergic system's stimulation, and reduction of excitotoxicity, inflammation, apoptosis, oxidative stress, mitochondrial dysfunction, and autophagy. Moreover, the possible roles of nAChRs in neurogenesis, synaptogenesis, and stimulation of neurotrophic factors expression have been reported previously. On the other hand, the majority of the above-mentioned mechanisms were found to be common in both brain ischemia pathogenesis and cognitive function tuning. Therefore, it seems that nAChRs might be known as key regulators in the control of ischemia pathology, and their modulation could be considered as a new avenue in the multi-target treatment of post-stroke cognitive impairment.
卒中后残疾，如认知障碍，给医疗保健系统带来了复杂的状况和巨大的经济负担。对于这些合并症，目前还没有发现有效的治疗方法。烟碱型乙酰胆碱受体（nAChRs）是参与多种行为和神经生物学功能的多功能受体。在脑缺血期间，谷氨酸积累增加会导致神经元兴奋性毒性和线粒体功能障碍。这些异常导致氧化剂水平升高，在梗死区的神经元死亡和细胞凋亡中起关键作用。此外，细胞因子和炎症因子的回忆在缺血性损伤的加剧中起着突出的作用。同样，神经营养因子的不足导致缺血性大脑中的突触功能障碍和认知障碍。值得注意的是，nAChRs 通过各种信号通路可以参与治疗方法，如胆碱能系统的刺激，减少兴奋性毒性、炎症、细胞凋亡、氧化应激、线粒体功能障碍和自噬。此外，先前已经报道了 nAChRs 在神经发生、突触发生和神经营养因子表达刺激中的可能作用。另一方面，上述大多数机制在脑缺血发病机制和认知功能调节中被发现是共同的。因此，nAChRs 似乎可以作为控制缺血性病理的关键调节剂，其调节可以被认为是卒中后认知障碍多靶点治疗的一个新途径。
