Anti-apoptotic effects of BDNF-TrkB signaling in the treatment of hemorrhagic stroke
Yu Hasegawa, Cao Cheng, Kenyu Hayashi, Yushin Takemoto, Shokei Kim‐Mitsuyama
Abstract
Stroke is a primary cause of death and a leading cause of disability throughout the world. Although researchers have long studied ways for improving mortality and morbidity, few effective treatments are available for patients with stroke. Effective treatments for hemorrhagic stroke (HS) remain a major challenge, but basic research on HS has revealed pivotal cytotoxic processes and potent therapeutic candidates. Many cytotoxic changes such as apoptosis, oxidative stress, and inflammation participate in the pathogenesis of HS, and antiapoptotic effects have been the focus of therapeutic candidates for HS. Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase B (TrkB), are known to play a pivotal role in antiapoptotic effects and are widely studied in experimental stroke research. In this review, we focus on the antiapoptotic effects of BDNF-TrkB signaling activation in HS. We first introduce BDNF-TrkB signaling in the apoptotic cascade and then summarize the deficiency of the signaling. Subsequently, we discuss the antiapoptotic effect of BDNF-TrkB signaling on subarachnoid hemorrhage, intracerebral hemorrhage, hemorrhagic transformation after ischemic stroke, stroke onset, and vascular dementia. Finally, this review discusses the potential beneficial effects for patients with HS. These comprehensive findings of the antiapoptotic effects of BDNF-TrkB signaling can contribute to the development of a novel therapeutic agent for patients with HS.