Strong neurogenesis, angiogenesis, synaptogenesis, and antifibrosis of hepatocyte growth factor in rats brain after transient middle cerebral artery occlusion.
Hepatocyte growth factor (HGF) and glial cell line-derived neurotrophic factor (GDNF) are strong neurotrophic factors. However, their potentials in neurogenesis, angiogenesis, synaptogenesis, and antifibrosis have not been compared. Therefore, we investigated these effects of HGF and GDNF in cerebral ischemia in the rat. Wistar rats were subjected to 90 min of transient middle cerebral artery occlusion (tMCAO). Immediately after reperfusion, HGF or GDNF was given by topical application. BrdU was injected intraperitoneally twice daily 1, 2, and 3 days after tMCAO. On 14 day, we histologically evaluated infarct volume, antiapoptotic effect, neurogenesis, angiogenesis, synaptogenesis, and antifibrosis. Both HGF and GDNF significantly reduced infarct size and the number of TUNEL-positive cells, but only HGF significantly increased the number of BrdU-positive cells in the subventricular zone, and 5'-bromo-2'-deoxyuridine -positive cells differentiated into mature neurons on the ischemic side. Enhancement of angiogenesis and synaptogenesis at the ischemic boundary zone was also observed only in HGF-treated rats. HGF significantly decreased the glial scar formation and scar thickness of the brain pia mater after tMCAO, but GDNF did not. Our study shows that both HGF and GDNF had significant neurotrophic effects, but only HGF can promote the neurogenesis, angiogenesis, and synaptogenesis and inhibit fibrotic change in brains after tMCAO.
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Shikatacho, Okayama, Japan.
Jingwei
J
Shang
Kentaro
K
Deguchi
Yasuyuki
Y
Ohta
Ning
N
Liu
Xuemei
X
Zhang
Fengfeng
F
Tian
Toru
T
Yamashita
Yoshio
Y
Ikeda
Tohru
T
Matsuura
Hiroshi
H
Funakoshi
Toshikazu
T
Nakamura
Koji
K
Abe
D000818:Animals; D001921:Brain / Q000098:blood supply*; D004195:Disease Models, Animal; D005355:Fibrosis; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000502:physiology / Q000627:therapeutic use; D017228:Hepatocyte Growth Factor / Q000502:physiology* / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D018919:Neovascularization, Physiologic; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000473:pathology*
D051100:Glial Cell Line-Derived Neurotrophic Factor; D017228:Hepatocyte Growth Factor