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Neurosci Lett. 2019 Nov 27:134657. doi: 10.1016/j.neulet.2019.134657. [Epub ahead of print]

Effects of mesencephalic astrocyte-derived neurotrophic factor on cerebral angiogenesis in a rat model of cerebral ischemia.

Author information

1
Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400013, China; Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing, 400013, China.
2
Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
3
Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
4
College of Clinical Medicine, Chongqing Medical and Pharmaceutical College, Chongqing, 401331, China.
5
Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
6
Department of Neurology, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400013, China; Chongqing Key Laboratory of Neurodegenerative Diseases, Chongqing, 400013, China. Electronic address: majingxi@ucas.ac.cn.

Abstract

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.

KEYWORDS:

Angiogenesis; Cerebral ischemia; Mesencephalic astrocyte-derived neurotrophic factor

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