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

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.

• Authors: Jianfeng Liu, Tianhua Zhang, Yingying Wang, Chengqing Si, Xudong Wang, Rui-Tao Wang, Zhonghua Lv
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 4 Pg. 3791-3806 (02 21 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 32084011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Clusterin
• Cytokines
• Flavonoids
• Methylamines
• Neuroprotective Agents
• baicalin
• trimethyloxamine
• trimethylamine

Topics

• Animals
• Brain (pathology)
• Clusterin (blood)
• Cytokines (blood)
• Disease Models, Animal
• Flavonoids (pharmacology, therapeutic use)
• Gastrointestinal Microbiome (drug effects)
• Inflammation (blood, drug therapy, pathology)
• Male
• Methylamines (blood)
• Mice
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Reperfusion Injury (blood, drug therapy, pathology)