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P2X4 Inhibition reduces microglia inflammation and apoptosis by NLRP3 and improves nervous system defects in rat
Wei He1, Qian Wang2, Weiping Sha1
1Department of Orthopaedic, The Affiliated Zhangjiagang Hospital of Soochow University, Suzhou, China.
Abstract:
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.
Insights
Inhibition of the purinergic receptor P2X4 (adenosine triphosphate-gated cation channel) significantly improved outcomes in a traumatic brain injury (TBI) rat model. Targeting P2X4 reduced inflammation and brain edema, offering a potential therapeutic strategy for TBI.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- The purinergic receptor P2X4 (P2X4) is an adenosine triphosphate (ATP)-gated cation channel crucial for various biological processes.
- Traumatic brain injury (TBI) involves complex pathological mechanisms including inflammation and cell death.
Purpose of the Study:
- To investigate the role and therapeutic potential of P2X4 in a rat model of TBI.
- To elucidate the underlying mechanisms involving P2X4 in TBI pathogenesis.
Main Methods:
- Real-time PCR and Western blot to assess P2X4 expression.
- Immunofluorescence, apoptosis assays, brain water content, and neurological scoring to evaluate TBI.
- Administration of the P2X4 antagonist 5-BDBD.
Main Results:
- P2X4 expression significantly increased in the injured brain areas of TBI rats at 48 hours.
- Treatment with the P2X4 antagonist 5-BDBD improved neurological deficits and reduced brain edema.
- P2X4 inhibition decreased microglial inflammation and apoptosis, with potential involvement of NLRP3.
Conclusions:
- P2X4 plays a significant role in TBI pathophysiology.
- Inhibiting P2X4 demonstrates therapeutic potential for TBI by mitigating neuroinflammation, apoptosis, and edema.
- Targeting P2X4 represents a promising strategy for TBI treatment.