Effect of P2X7R on neuroinflammation and brain edema after traumatic brain injury in mice

  Background  Inflammation and brain edema after traumatic brain injury (TBI) are important factors causing severe complications such as increased intracranial pressure. Purinergic ligand-gated ion channel 7 receptor (P2X7R) plays an important role in mediating innate immune response. Its activation can trigger the activation of inflammatory response, which is closely related to the inflammatory response of nervous system diseases.

  Objective  To observe the effect of P2X7R on neuroinflammation and brain edema after traumatic brain injury in mice.

  Methods  The classic controlled cortical impaction model was utilized to establish a mouse model of traumatic brain injury. The morphology of microglia and the content of P2X7R were observed by immunofluorescence. The water content of mouse brain tissue was measured by wet-dry weight method. Lipopolysaccharide (LPS) was applied to microglia cell line (BV2 cell line) to simulate the activation of microglia after traumatic brain injury. The protein content of P2X7R in BV2 cell line was determined by Western blot. The expression levels of TNF-α, IL-1β, IL-6 and IL-12 in BV2 cell line were determined by ELISA. Conditioned medium co-culture was utilized to explore the effect of activated microglia on endothelial cells, and the protein content of claudin-5 in bEnd3 cell line was detected by Western blot.

  Results  The results of animal experiments showed that after acute traumatic brain injury, microglia were increased and significantly activated and P2X7R was mainly colocalized to the microglial cell. And inhibition of P2X7R could reduce the water content of brain tissue in mice with traumatic brain injury, and significantly alleviate brain edema. The results of cell experiments showed that the content of P2X7R, TNF-α, IL-1β, IL-6 and IL-12 in activated microglia was increased, while inhibition of P2X7R could reduce the secretion of the above inflammatory factors (P＜0.05). Co-culture experiment suggested that inhibition of P2X7R could increase the expression of tight junction protein in endothelial cells after traumatic brain injury.

  Conclusion  Inhibition of P2X7R can reduce neuroinflammation and brain edema secondary to acute traumatic brain injury in mice, but its mechanism needs further study.