Interplay between Gut Microbiota and NLRP3 Inflammasome in Intracerebral Hemorrhage

Abstract

The pathophysiological process of intracerebral hemorrhage (ICH) is very complex, involving various mechanisms such as apoptosis, oxidative stress and inflammation. As one of the key factors, the inflammatory response is responsible for the pathological process of acute brain injury and is associated with the prognosis of patients. Abnormal or dysregulated inflammatory responses after ICH can aggravate cell damage in the injured brain tissue. The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a multiprotein complex distributed in the cytosol, which can be triggered by multiple signals. The NLRP3 inflammasome is activated after ICH, thus promoting neuroinflammation and aggravating brain edema. In addition, there is evidence that the gut microbiota is crucial in the activation of the NLRP3 inflammasome. The gut microbiota plays a key role in a variety of CNS disorders. Changes in the diversity and species of the gut microbiota affect neuroinflammation through the activation of the NLRP3 inflammasome and the release of inflammatory cytokines. In turn, the gut microbiota composition can be influenced by the activation of the NLRP3 inflammasome. Thereby, the regulation of the microbe–gut–brain axis via the NLRP3 inflammasome may serve as a novel idea for protecting against secondary brain injury (SBI) in ICH patients. Here, we review the recent evidence on the functions of the NLRP3 inflammasome and the gut microbiota in ICH, as well as their interactions, during the pathological process of ICH.

Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions

“…Increased levels of NLRP3, ASC, IL-18 and caspase-1 have been observed not only in animal models, but also in human patients with ALS [ 106 , 109 , 110 ].Therefore, NLRP3 inflammasome may become a potential target for intervention of neuronal death. The activation of NLRP3 inflammasome can be divided into two stages: initiation and activation [ 111 ]. Risk signals such as oxidative stress, lysosomal damage and Ca 2+ mobilization can be identified through the damage-related molecular pattern (DAMPs) or the pathogen-related molecular pattern (PAMPs), thereby initiating the assembly of NLRP3 inflammasome [ 112 ].…”

“…Risk signals such as oxidative stress, lysosomal damage and Ca 2+ mobilization can be identified through the damage-related molecular pattern (DAMPs) or the pathogen-related molecular pattern (PAMPs), thereby initiating the assembly of NLRP3 inflammasome [ 112 ]. Activated caspase-1 can generate cell membrane pores and initiate cell apoptosis [ 111 ]. Trimethylamine oxide (TMAO) and short-chain fatty acids (SCFAs) are important metabolites of intestinal microorganisms.…”

Crosstalk between ubiquitin ligases and ncRNAs drives cardiovascular disease progression

“…Therapeutically, lithium improved neurovascular remodeling by upregulating miR-124 expression, decreasing REST abundance and inhibiting deubiquitination of peri-infarct brain tissues and proteins on the 4th day post-stroke ( 102 ). Inhibition of FBXO3 by siRNA alleviates cerebral I/R injury by suppressing ubiquitination and degradation of HIPK2 via the UPS ( 103 ), while TGR5 siRNA reduces the inhibitory effect of the E3 ubiquitin ligase Pellino3 on caspase-8 and NLRP3, thereby exacerbating cerebrovascular stroke ( 104 , 105 ).…”

The role of gut microorganisms and metabolites in intracerebral hemorrhagic stroke: a comprehensive review

“…Upon stimulation by extracellular inflammatory stimuli, the NLRP3 inflammasome becomes activated, leading to the activation of pro-caspase-1 into caspase-1 and the subsequent release of inflammatory mediators such as IL-1β and IL-18. Additionally, Gasdermin D (GSDMD) is dissociated and interacts with the cell membrane to form pores, thereby initiating pyroptosis ( Zhang et al, 2022 ).…”