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Cell Mol Neurobiol. 2019 Aug;39(6):883-898. doi: 10.1007/s10571-019-00687-3. Epub 2019 May 28.

Neuroprotection of Resveratrol Against Focal Cerebral Ischemia/Reperfusion Injury in Mice Through a Mechanism Targeting Gut-Brain Axis.

Author information

1
Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou, 450000, Henan, China.
2
Department of Anesthesiology, People's Hospital of Zhengzhou University and Henan Provincial People's Hospital, Zhengzhou, Henan, China.
3
Department of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou, 450000, Henan, China. lyq260703@163.com.

Abstract

Increasing evidences have shown that resveratrol could protect the brain from ischemic injury; the mechanisms underlying its neuroprotective effects are multifactorial and not fully understood. It remains unclear whether resveratrol could exert neuroprotection through modulating gut-brain axis, which plays important roles in stroke pathology. In this study, C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion for 3 days. Resveratrol, when applied immediately after MCAO onset for 3 days, promoted Th1/Th2 balance towards Th2 polarization and skewed Treg/Th17 balance towards Treg in the small intestinal lamina propria (SI-LP), and decreased small intestinal pro-inflammatory cytokines expression through modulating intestinal flora at 3 days post-ischemia (dpi). Resveratrol attenuated cerebral ischemia-induced increase in the epithelial and vascular permeability of small intestine as evidenced by reduced evans blue extravasasion and decreased protein leakage by feces/plasma albumin ratio at 3 dpi. The blood levels of pro-inflammatory cytokines at 3 dpi were also attenuated by resveratrol due to inhibiting intestinal pro-inflammatory immunity and decreasing epithelial and vascular permeability. Resveratrol robustly protected against post-stroke inflammation-induced blood-brain barrier disruption not only in the cortex but also in the striatum at 3 dpi. Furthermore, resveratrol mediated smaller cerebral infarcts and less neurological deficits via decreasing the levels of pro-inflammatory cytokines in the peri-infarct area at 3 dpi. Our results for the first time demonstrated that resveratrol may inhibit systemic post-stroke inflammation and neuroinflammation via modulating intestinal flora-mediated Th17/Tregs and Th1/Th2 polarity shift in SI-LP, which may be one of the mechanisms underlying the neuroprotective effects of resveratrol.

KEYWORDS:

Gut-brain axis; Inflammation; Intestinal immunity; Resveratrol; Stroke

PMID:
31140018
DOI:
10.1007/s10571-019-00687-3
[Indexed for MEDLINE]

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