The Role Of Microvesicles Mediated By P2X7Receptor In TBI

Traumatic brain injury (TBI) is defined as damage to the brain resulting from an external mechanical force, such as that caused by rapid acceleration or deceleration, blast waves, crush, an impact or penetration by a projectile. It can lead to temporary or permanent impairment of cognitive,physical and psychosocial functions. TBI is the leading cause of death and disability for people under the age of45years. Indeed, worldwide,10million deaths and/or hospitalizations annually are directly attributable to TBI and an estimated57million currently alive people have experienced such brain injury.TBI is not a single pathophysiological event but a complex disease process, and it causes structural damage and functional deficits that are due to both primary and secondary injury mechanisms. As the primary injury occurs immediately after the moment of trauma, it can only be preventable. By contrast, the elongated nature of secondary injury development provides a window of opportunity for therapeutic intervention, which may prevent and/or reduce secondary brain damage and improve long-term patient outcome. To date, however, promising results from preclinical studies of potential TBI treatments have not been translated into successful outcomes in clinical trials.Many biochemical derangements that are responsible for secondary injury have been identified such as glutamate excitotoxicity, perturbation of cellular calcium homeostasis increased free radical generation and lipid peroxidation,mitochondrial dysfunction and inflammation. In recent years, ATP involved in the nerve secondary injury pathological process is more concerned. High concentrations of ATP involved in the activation of microglia by P2X7receptors mediated microvesicles release1L-1β. We believe that local high concentrations of ATP may be continued to nerve damage after traumatic brain injury.In our study, using SD rats were constructed in accordance with the the Marmarou heavy freefall model animal model of TBI, and then passed to a P2X7receptor antagonist A438079to inhibit the function of the P2X7receptor, useing of immunofluorescence staining,western blot and Morris water maze and other technical means to observe the impact of TBI injury. It was found that the damage zone P2X7-positive microglia activation significantly transformed into amoeba-like, around its many P2X7receptor and IBA-1-positive microbubbles. A438079and FTY720(immunosuppressant properties of inhibitor microvesicles release) can significantly reduce the number of microvesicles in cortical damage zone, reduces the local neuronal apoptosis and neuronal loss, and reduce the extent of local gelatinized; Western blot. results showed that FTY720inhibit1L-1beta release. In the Morris water maze test, A438079also significantly increased the space learning memory ability after the TBI.On the basis of these results, we indicate that the local ATP are involved in the pathological process of nerve secondary injury by P2X7receptors after TBI, inhibition of P2X7receptors may become a new target of TBI treatment.