Atorvastatin alleviates microglia-mediated neuroinflammation via modulating the microbial composition and the intestinal barrier function in ischemic stroke mice

Zhang, Peipei; Zhang, Xiangjian; Huang, Yuanxiang; Chen, Junmin; Shang, Wenyan; Shi, Guang; Zhang, Lan; Zhang, Cong; Chen, Rong

doi:10.1016/j.freeradbiomed.2020.11.032

Cited by 58 publications

(39 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After ICH, we found significant intestinal barrier damage as inferred from the concentration of FITC-dextran in the plasma. The intestinal barrier consists of three components: surface mucus, the epithelial layer, and immune defenses ( Zhang et al, 2021 ). Tight junction proteins such as Claudin-1 and Occludin in the epithelial layer are essential for gut integrity ( Saitou et al, 2000 ).…”

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Dysbiosis Induced by Intracerebral Hemorrhage Aggravates Neuroinflammation in Mice

Zhou

Shao

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

Intracerebral hemorrhage (ICH) induces a strong hematoma-related neuroinflammatory reaction and alters peripheral immune homeostasis. Recent research has found that gut microbiota plays a role in neurodegeneration and autoimmune diseases by regulating immune homeostasis and neuroinflammation. Therefore, we investigated the relationship between ICH, microbiota alteration, and immune responses after hematoma-induced acute brain injury. In our study, we used a mouse model of ICH, and 16S ribosomal RNA sequencing showed that ICH causes gut microbiota dysbiosis, which in turn affects ICH outcome through immune-mediated mechanisms. There was prominent reduced species diversity and microbiota overgrowth in the dysbiosis induced by ICH, which may reduce intestinal motility and increase gut permeability. In addition, recolonizing ICH mice with a normal health microbiota ameliorates functional deficits and neuroinflammation after ICH. Meanwhile, cell-tracking studies have demonstrated the migration of intestinal lymphocytes to the brain after ICH. In addition, therapeutic transplantation of fecal microbiota improves intestinal barrier damage. These results support the conclusion that the gut microbiome is a target of ICH-induced systemic alteration and is considered to have a substantial impact on ICH outcome.

show abstract

Section: Discussionmentioning

confidence: 99%

Gut Microbiota Dysbiosis Induced by Intracerebral Hemorrhage Aggravates Neuroinflammation in Mice

Zhou

Shao

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Oral gavage of SCFAs-producing bacteria or SCFAs supplementation also alleviated neurological deficits and improved poststroke recovery by reducing IL-17 + gdT cells in the ischemic brain (57,58). Recently, Zhang et al found that atorvastatin significantly alleviated the defects in sensorimotor behaviors and reduced microglia-mediated neuroinflammation by increasing the abundance of Firmicutes and Lactobacillus, decreasing the abundance of Bacteroidetes abundance, increasing fecal butyrate level, promoting intestinal barrier function, as well as regulating intestinal immune function (reduced monocyte chemotactic protein 1(MCP-1), tumor necrosis factor-a(TNF-a) and increased IL-10) in the mice with permanent MCAO (72). Calorie restriction also can promote ischemic stroke rehabilitation via enriching the abundance of Bifidobacterium (73).…”

Section: Ischemic Strokementioning

confidence: 99%

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention

Yuan

2021

Front. Immunol.

View full text Add to dashboard Cite

Acute central nervous system (CNS) injuries, including stroke, traumatic brain injury (TBI), and spinal cord injury (SCI), are the common causes of death or lifelong disabilities. Research into the role of the gut microbiota in modulating CNS function has been rapidly increasing in the past few decades, particularly in animal models. Growing preclinical and clinical evidence suggests that gut microbiota is involved in the modulation of multiple cellular and molecular mechanisms fundamental to the progression of acute CNS injury-induced pathophysiological processes. The altered composition of gut microbiota after acute CNS injury damages the equilibrium of the bidirectional gut-brain axis, aggravating secondary brain injury, cognitive impairments, and motor dysfunctions, which leads to poor prognosis by triggering pro-inflammatory responses in both peripheral circulation and CNS. This review summarizes the studies concerning gut microbiota and acute CNS injuries. Experimental models identify a bidirectional communication between the gut and CNS in post-injury gut dysbiosis, intestinal lymphatic tissue-mediated neuroinflammation, and bacterial-metabolite-associated neurotransmission. Additionally, fecal microbiota transplantation, probiotics, and prebiotics manipulating the gut microbiota can be used as effective therapeutic agents to alleviate secondary brain injury and facilitate functional outcomes. The role of gut microbiota in acute CNS injury would be an exciting frontier in clinical and experimental medicine.

show abstract

“…Interestingly, oral administration of Bifidobacterium longum has achieved similar neuroprotective effects as Panax Notoginsenoside extract ( Li et al., 2018a ), which serves as an example how we could take advantage of specific species from gut microbiota for stroke recovery. In addition, atorvastatin and lactulose have already been demostrated to repair gut barrier, reduce gut inflammation and restore gut microbiota after stroke, providing novel startegies to improve stroke outcome ( Yuan et al., 2021 ; Zhang et al., 2021 ). In the future, both basic research and clinical studies on gut microbiota will open novel avenues not only for stroke therapy, but also for other brain disorders.…”

Section: Discussionmentioning

confidence: 99%

“…When stroke induces dysbiosis of gut microbiota, Enterobacteriaceae in gut microbiota can also accelerate systematic inflammation thus exacerbate brain damage in both mouse model and patients samples, which may serve as a promising therapeutic target ( Xu et al., 2021 ). In another animal study, atorvastatin restored gut microbiota homeostasis, contributing to its anti-inflammatory functions after stroke ( Zhang et al., 2021 ).…”

Section: The Interplay Between Stroke and Gut Microbiotamentioning

confidence: 99%

The Impact of Gut Microbiota on Post-Stroke Management

Zhao

Liu

Yan

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Atorvastatin alleviates microglia-mediated neuroinflammation via modulating the microbial composition and the intestinal barrier function in ischemic stroke mice

Cited by 58 publications

References 62 publications

Gut Microbiota Dysbiosis Induced by Intracerebral Hemorrhage Aggravates Neuroinflammation in Mice

Gut Microbiota Dysbiosis Induced by Intracerebral Hemorrhage Aggravates Neuroinflammation in Mice

Gut Microbiota and Acute Central Nervous System Injury: A New Target for Therapeutic Intervention

The Impact of Gut Microbiota on Post-Stroke Management

Contact Info

Product

Resources

About