-Nlrp3 is involved in the neuroprotection of phosphoglycerate mutase 5 deficiency in traumatic brain injury mice.

INTRODUCTION

Gut-microbiota-brain axis is a potential treatment to decrease the risk of chronic traumatic encephalopathy following traumatic brain injury (TBI). Phosphoglycerate mutase 5 (PGAM5), a mitochondrial serine/threonine protein phosphatase, resides in mitochondrial membrane and regulates mitochondrial homeostasis and metabolism. Mitochondria mediates intestinal barrier and gut microbiome.

OBJECTIVES

This study investigated the association between PGAM5 and gut microbiota in mice with TBI.

METHODS

The controlled cortical impact injury was established in mice with genetically-ablated () or wild type, and WT male mice were treated with fecal microbiota transplantation (FMT) from male mice or (). Then the gut microbiota abundance, blood metabolites, neurological function, and nerve injury were detected.

RESULTS

Treated with antibiotics for suppressing gut microbiota in mice partially relieved the role of deficiency in the improvement of initial inflammatory factors and motor dysfunction post-TBI. knockout exhibited an increased abundance of in mice. FMT from male mice enabled better maintenance of amino acid metabolism and peripherial environment than that in TBI-vehicle mice, which suppressed neuroinflammation and improved neurological deficits, and was negatively associated with intestinal mucosal injury and neuroinflammation post-TBI. Moreover, treatment ameliorated neuroinflammation and nerve injury by regulating Nlrp3 inflammasome activation in cerebral cortex with TBI.

CONCLUSION

Thus, the present study provides evidence that Pgam5 is involved in gut microbiota-mediated neuroinflammation and nerve injury, with -Nlrp3 contributing to peripheral effects.