Study on Neuroprotective Function and Mechanism of 7,8-DHF-Activated Neurotrophic Factor Receptor TrkB in Intracerebral Hemorrhage

Abstract

Background: 7,8-dihydroxyflavone (DHF) is a potent agonist of tropomyosin-related kinase B (TrkB), which binds to TrkB and causes TrkB phosphorylation, reducing cell apoptosis improves the stability of the nervous system. It has been shown to play a therapeutic role in various animal disease models, such as ischemic stroke, traumatic brain injury, and Alzheimers disease. To investigate the protective effect of 7,8-dihydroxyflavone (7,8-DHF) on neuronal cells, we explore the improvement effect of 7,8-DHF on intracerebral hemorrhage (ICH) by activating the TrkB signaling pathway, and study the related mechanism. Methods: Venous blood samples were collected from patients with ICH before and after treatment and normal people in a fasted state, and mRNA expression levels of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), phosphatidylinositol 3 kinases (PI3K), protein kinase B (AKT), mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (Erk), and other genes were determined by real-time quantitative PCR (RT-qPCR). An animal model of C57BL/6J mice with ICH was established by injecting collagenase and heparin into the cerebral striatum, with normal C57BL/6J mice as controls. Both groups were injected intraperitoneally or intravenously with DHF or normal saline once a day for two weeks before euthanasia. The neuronal and glial cells of the cerebral cortex striatum were collected from the mice, from which the apoptosis of neuronal and glial cells was detected by ELISA, and mRNA expression of BDNF, TrkB, PI3K, AKT, MAPK, and Erk genes were detected by qPCR. Results: The RNA expression (BDNF, TrkB, PI3K, AKT, MAPK, and Erk) in the ICH treat group was significantly higher than in the ICH group, without significant difference in RNA (BDNF, TrkB, PI3K, AKT, MAPK, Erk) between ICH treat group and Normal group. Compared with the ICH group, the apoptosis of neuronal and glial cells of ICH mice significantly decreased. At the same time, the expression levels of BDNF, TrkB, PI3K, AKT, MAPK, and Erk were significantly increased. DHF promotes the expression of cellular neurotrophic factor-related genes and proteins in ICH mice and neuronal cell models. Conclusion: 7,8-DHF can inhibit the apoptosis of neuronal and glial cells, promote their proliferation, increase mRNA expression levels of neurotrophin and its receptors, and activate neurotrophic factor receptors. 7,8-DHF has the potential to protect neuronal cells and possibly improve ICH.