Rui Mao1 • Ningning Zong1 • Yujie Hu1 • Ying Chen1 • Yun Xu1,2,3,4,51 Department of Neurology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China
2 The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing 210008, China
3 Jiangsu Key Laboratory for Molecular Medicine, Medical School of Nanjing University, Nanjing 210008, China
4 Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing 210008, China
5 Nanjing Neurology Clinic Medical Center, Nanjing 210008, China
Abstract
Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy. Even so, patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury. It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies. Regarding the pathogenesis, multiple pathological events trigger the activation of cell death pathways. Particular attention should be devoted to excitotoxicity, oxidative stress, and inflammatory responses. Thus, in this article, we first review the principal mechanisms underlying neuronal death mediated by these significant events, such as intrinsic and extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, and autophagic cell death. Then, we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.
Keywords
Ischemic stroke; Neuronal death; Mechanisms; Therapeutic strategy
