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Research Paper|Volume 12, Issue 4|pp 3791—3806

Baicalin ameliorates neuropathology in repeated cerebral ischemia-reperfusion injury model mice by remodeling the gut microbiota

Jianfeng Liu1, Tianhua Zhang2, Yingying Wang3, Chengqing Si1, Xudong Wang1, Rui-Tao Wang4, Zhonghua Lv5
  • 1Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
  • 2Department of Vascular Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
  • 3Department of Computer Science, Hong Kong Baptist University, Hong Kong, China
  • 4Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
  • 5Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin 150081, China
* Equal contribution and co-first authors
Received: November 6, 2019Accepted: February 4, 2020Published: February 21, 2020
https://doi.org/10.18632/aging.102846

Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

We investigated the neuroprotective effects of baicalin and the role of gut microbiota in a mouse model of cerebral ischemia-reperfusion injury. Repeated cerebral ischemia-reperfusion significantly increased plasma levels of trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and clusterin (a neuroinflammation biomarker). These changes correlated with cognitive decline; short-term memory deficits; abnormal long term potentiation (LTP); decreased functional connectivity (FC) between various brain regions; reduced plasticity and dendritic spine density in the hippocampus; increased levels of the pro-inflammatory cytokines IL-1β, IL-6, and TNFα; and altered the gut microbial composition. Treatment with 50-100 mg/Kg baicalin for 7 days after cerebral ischemia-reperfusion significantly restored normal plasma levels of TMA, TMAO, and clusterin. Baicalin treatment also suppressed neuroinflammation, remodeled the gut microbial composition back to normal, and improved cognition, memory, LTP, cerebral FC, and hippocampal neuronal plasticity. The neuroprotective effects of baicalin were diminished when mice undergoing repeated cerebral ischemia-reperfusion were pretreated with broad-spectrum antibiotics to deplete gut microbial populations. This suggests the neuroprotective effects of baicalin in cerebral ischemia-reperfusion injury are mediated by the gut microbiota. It thus appears that baicalin ameliorates neuropathology in a repeated cerebral ischemia-reperfusion model mice by remodeling the gut microbiota.