following hypoxia and ischemia events.163 In neurons, P2X4R has shown to stimulate activation of the inflammasome caspase-1 resulting in cytokines IL-18 and IL-β release, and in P2X4R knockout mice, impaired inflammasome signaling was reported to couple to the reduction of IL-β level.164 Inhibition of P2X4 receptors by antagonists prior to cerebral ischemia has resulted in an attenuation of the neuroinflammation response and health of neuronal tissue.165 Additionally, P2X4 receptor upregulation has been reported in several rodent models including mechanical allodynia,14 superoxide dismutase 1-mutation models of ALS,166 EAE model of multiple sclerosis,17 post spinal cord injury,164 formalin-induced inflammatory pain,167 TBI,168 and ischemia.165 These data support the central role that P2X4 receptors play in coordinating the microglial response to cellular injuries and/or diseases.
