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.