[Ischemic brain injury and hepatocyte growth factor].
Cerebral ischemia causes an irreversible and neurodegenerative disorder that may lead to progressive dementia and global cognitive deterioration. Since the overall process of ischemic brain injuries is extremely complex, treatment with endogenous multifunctional factors would be better choices for preventing complicated ischemic brain injuries. Hepatocyte growth factor, HGF, is a multifunctional cytokine originally identified and purified as a potent mitogen for hepatocyte. The activation of the c-Met/HGF receptor evokes diverse cellular responses, including mitogenic, morphogenic, angiogenic and anti-apoptotic activities in various types of cell. Previous studies showed that HGF and c-Met were expressed in various brain regions under normal conditions and that HGF enhanced the survival of hippocampal and cortical neurons during the aging of cells in culture. The protective effects of HGF on in vivo ischemic brain injuries and their mechanisms have not fully understood. To elucidate therapeutic potencies of HGF for ischemic brain injuries, we examined effects of HGF on ischemia-induced learning and memory dysfunction, neuronal cell death and endothelial cell damage by using the 4-vessel occlusion model and the microsphere embolism model in rats. Our findings suggested that treatment with HGF was capable of protecting hippocampal neurons against ischemia-induced cell death through the prevention of apoptosis-inducing factor translocation to the nucleus. Furthermore, we demonstrated that HGF had the ability to prevent tissue degeneration and improved learning and memory function after cerebral embolism, possibly through prevention of cerebral vessel injuries. As HGF has a potent cerebroprotective effect, it could be a prospective agent for the therapy against complicated ischemic brain diseases.
Takeo
Satoshi
S
Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, Horinouchi, Hachioji City, Japan.
Takagi
Norio
N
Takagi
Keiko
K
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use*; D006801:Humans; D007859:Learning Disabilities / Q000188:drug therapy; D008569:Memory Disorders / Q000188:drug therapy; D019636:Neurodegenerative Diseases / Q000517:prevention & control; D009474:Neurons; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000502:physiology; D051381:Rats
D018696:Neuroprotective Agents; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met