Yangyin Tongnao granules enhance neurogenesis in the peri-infarct area and upregulate brain-derived neurotrophic factor and vascular endothelial growth factor after focal cerebral ischemic infarction in rats

Mol Biol Rep. 2019 Aug;46(4):3817-3826. doi: 10.1007/s11033-019-04824-5. Epub 2019 Apr 20.

Abstract

Yangyin Tongnao granules (YYTNG) have been extensively applied in the treatment of brain injury, mainly due to its antioxidant effects, inhibition of apoptosis, and enhancement of blood circulation. To analyze the effect of YYTNG on the recovery of neurological function and neurogenesis in the peri-infarct area after cerebral ischemic infarction in rats and to elucidate its role in the neuroprotective mechanism of stroke, Sprague-Dawley (SD) rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. Rats were randomly divided into five groups: sham, MCAO, and YYTNG-treated rats given doses of 0.83, 1.65, or 3.3 g kg-1 day-1. The YYTNG-treated groups (1.65 and 3.3 g kg-1 day-1) showed higher neurological scores and a lower infarct volume than the MCAO group on day 3 after MCAO. Furthermore, the YYTNG-treated groups (0.83, 1.65, and 3.3 g kg-1 day-1) showed higher neurological scores on day 7 after MCAO. The number of BrdU+/nestin+, BrdU+/NeuN+, and BrdU+/GFAP+ cells in the peri-infarct area 7 days after MCAO was significantly increased in the YYTNG-treated groups in a dose-dependent manner. The protein expression levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) were significantly higher in all three YYTNG-treated groups than in the MCAO group. Based on these results, administration of YYTNG post ischemia could ameliorate neurological function deficits in rats with MCAO. The therapeutic effect of YYTNG may be due to the promotion of neurogenesis in the peri-infarct area and the upregulation of neuroprotective factors BDNF and VEGF in MCAO rats.

Keywords: BDNF; NPCs; Neurogenesis; VEGF; Yangyin Tongnao granules.

MeSH terms

  • Animals
  • Astrocytes
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Differentiation / drug effects
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / metabolism
  • Neurogenesis / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • Vascular Endothelial Growth Factor A