Strong neurogenesis, angiogenesis, synaptogenesis, and antifibrosis of hepatocyte growth factor in rats brain after transient middle cerebral artery occlusion

Jingwei Shang, Kentaro Deguchi, Yasuyuki Ohta, Ning Liu, Xuemei Zhang, Fengfeng Tian, Toru Yamashita, Yoshio Ikeda, Tohru Matsuura, Hiroshi Funakoshi, Toshikazu Nakamura, Koji Abe

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)86-95
Number of pages10
JournalJournal of Neuroscience Research
Volume89
Issue number1
DOIs
Publication statusPublished - Jan 2011

Keywords

  • Angiogenesis
  • Antifibrosis
  • Cerebral ischemia
  • Neurogenesis
  • Synaptogenesis

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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