P2X4 Inhibition reduces microglia inflammation and apoptosis by NLRP3 and improves nervous system defects in rat brain trauma model.

The purinergic receptor P2X4 is an adenosine triphosphate (ATP)-gated cation channel, which plays an essential role in regulating various biological activities in the organism. This study was designed to investigate the potential role and mechanism of P2X4 in the traumatic brain injury (TBI) rat model. Real-time PCR, Western blot, immunofluorescence, apoptosis, brain water content and neurological score analysis were evaluated. We found that the expression level of P2X4 surrounding the injured area of the brain in the TBI rat model increased significantly after 48 h. Following the P2X4 selective antagonist 5-BDBD treatment, the neurological damage after TBI was significantly improved and brain edema was reduced. The inhibition of P2X4 effectively reduced the inflammation and apoptosis of microglia, and NLRP3 may be involved in this process. Our results indicate that inhibition of P2X4 may be a potential therapeutic approach for TBI by reducing the occurrence of inflammation and apoptosis of microglia, alleviating brain edema, and improving neurological deficits.