Hepatocyte growth factor reduces infarct volume after transient focal cerebral ischemia in rats.
Hepatocyte growth factor (HGF) was originally discovered as a powerful mitogen for hepatocytes. HGF functions both as a neurotrophic factor as well as an angiogenetic factor. Furthermore, HGF has an anti-apoptotic effect on vascular endothelial cells. The present study examined the neuroprotective effect of HGF after transient focal cerebral ischemia in rats, in which an anti-apoptotic and an angiogenetic effect of HGF was assumed to contribute to the reduction of the infarct volume. The intraventricular administration of human recombinant HGF (90 micrograms) significantly reduced the infarct volume after 120 minutes occlusion of both the right middle cerebral artery (MCA) and the bilateral common carotid arteries (CCAs). In a separate series of experiments, we investigated both the anti-apoptotic effect on neurons and the angiogenetic effect of HGF histopathologically. The number of survival neurons and vascular lumina in the HGF group were significantly higher than those in the vehicle group. A large number of TUNEL positive neurons were observed in the inner boundary of the infarct area in the vehicle group, whereas only a few TUNEL positive neurons were observed in a corresponding area in the HGF group. In the HGF group, Bcl-2 protein was obviously represented in survival neurons as well as in vascular endothelial cells and in glial cells subjected to ischemia. These data suggest that HGF prevents apoptotic neuronal cell death by upregulating the production of Bcl-2 protein and by an angiogenetic effect in the central nervous system which affected transient focal cerebral ischemia.
Tsuzuki
N
N
Department of Neurosurgery, National Defense Medical College, Tokorozawa, Japan.
Miyazawa
T
T
Matsumoto
K
K
Nakamura
T
T
Shima
K
K
Chigasaki
H
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000473:pathology*; D002544:Cerebral Infarction / Q000473:pathology*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007276:Injections, Intraventricular; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology
D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor