TY - JOUR
T1 - Effects of mesencephalic astrocyte-derived neurotrophic factor on cerebral angiogenesis in a rat model of cerebral ischemia
AU - Gao, Baobing
AU - Deng, Jing
AU - Zhang, Xiaogang
AU - Sun, Houchao
AU - Jia, Gongwei
AU - Li, Jiani
AU - Zhang, Keming
AU - Wan, Chengqun
AU - Wang, Linxi
AU - Yan, Liang Jun
AU - Cai, Zhiyou
AU - Ma, Jingxi
PY - 2020/1/10
Y1 - 2020/1/10
N2 - Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum stress-related protein that exhibits neuroprotective effects. Recent studies have shown that MANF promotes poststroke functional recovery in rats. However, the underlying mechanisms have not yet been fully understood. Here, we examined the effects of MANF on cerebral angiogenesis in a permanent middle cerebral artery occlusion model in rats. Recombinant human MANF was administered intracerebroventricularly 24 h after stroke. We performed neurobehavioral tests and assessed microvessel density, functional microvessels, and regional cerebral blood flow (rCBF), as well as detected angiogenic factors in the peri-infarct cerebral cortex. Results showed that MANF ameliorated neurobehavioral scores, promoted rCBF, upregulated the expression of CD34, as well as the total vessel surface area and the number of microvessel branch points, and activated the vascular endothelial growth factor (VEGF) pathway. In conclusion, our findings provide insight into the mechanisms of MANF in promoting functional recovery from ischemic stroke. Our results suggest that MANF improves neurobehavioral recovery from cerebral ischemic injury, and that this effect is mediated partly by its proangiogenic effects and augmentation of rCBF, which are possibly associated with VEGF.
AB - Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum stress-related protein that exhibits neuroprotective effects. Recent studies have shown that MANF promotes poststroke functional recovery in rats. However, the underlying mechanisms have not yet been fully understood. Here, we examined the effects of MANF on cerebral angiogenesis in a permanent middle cerebral artery occlusion model in rats. Recombinant human MANF was administered intracerebroventricularly 24 h after stroke. We performed neurobehavioral tests and assessed microvessel density, functional microvessels, and regional cerebral blood flow (rCBF), as well as detected angiogenic factors in the peri-infarct cerebral cortex. Results showed that MANF ameliorated neurobehavioral scores, promoted rCBF, upregulated the expression of CD34, as well as the total vessel surface area and the number of microvessel branch points, and activated the vascular endothelial growth factor (VEGF) pathway. In conclusion, our findings provide insight into the mechanisms of MANF in promoting functional recovery from ischemic stroke. Our results suggest that MANF improves neurobehavioral recovery from cerebral ischemic injury, and that this effect is mediated partly by its proangiogenic effects and augmentation of rCBF, which are possibly associated with VEGF.
KW - Angiogenesis
KW - Cerebral ischemia
KW - Mesencephalic astrocyte-derived neurotrophic factor
UR - http://www.scopus.com/inward/record.url?scp=85077107049&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2019.134657
DO - 10.1016/j.neulet.2019.134657
M3 - Article
C2 - 31785307
AN - SCOPUS:85077107049
VL - 715
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
ER -