P2Y12 receptor-mediated microglia activation involved in delayed encephalopathy after acute carbon monoxide poisoning.

To investigate the role of P2Y12 receptor-mediated microglia activation in delayed encephalopathy after acute carbon monoxide poisoning (DEACMP), we used static inhalation carbon monoxide to build DEACMP rat model. DEACMP rats were randomly assigned into DEACMP group and intervention group. A control goup was also set. The rats in intervention group received intraperitoneal injection of 100uM suramin (a P2Y12 receptor antagonist). In control group, the escape latency, level of microglia activation and ATP content were similar between different time points. In both DEACMP group and intervention group, the escape latency, level of microglia activation and ATP content were significanlty increased at 21th and 28th day. The hippocampal cells in DEACMP group and intervention group were severely and moderately, respectively, damaged at 21th and 28th day. Meanwhile, compared to control group, both DEACMP group and intervention group had significanlty longer escape latency, higher level of microglia activation and ATP content at 21th and 28th day. Compared to DEACMP group, the intervention group had significantly shorter escape latency and lower level of microglia activation at 21th and 28th day. These results suggested that the microglia activation regulated by ATP through P2Y12 receptor pathway might be closely related to the development of DEACMP.

Microglia and Macrophages in the Pathological Central and Peripheral Nervous Systems.

Microglia, the immunocompetent cells in the central nervous system (CNS), have long been studied as pathologically deteriorating players in various CNS diseases. However, microglia exert ameliorating neuroprotective effects, which prompted us to reconsider their roles in CNS and peripheral nervous system (PNS) pathophysiology. Moreover, recent findings showed that microglia play critical roles even in the healthy CNS. The microglial functions that normally contribute to the maintenance of homeostasis in the CNS are modified by other cells, such as astrocytes and infiltrated myeloid cells; thus, the microglial actions on neurons are extremely complex. For a deeper understanding of the pathophysiology of various diseases, including those of the PNS, it is important to understand microglial functioning. In this review, we discuss both the favorable and unfavorable roles of microglia in neuronal survival in various CNS and PNS disorders. We also discuss the roles of blood-borne macrophages in the pathogenesis of CNS and PNS injuries because they cooperatively modify the pathological processes of resident microglia. Finally, metabolic changes in glycolysis and oxidative phosphorylation, with special reference to the pro-/anti-inflammatory activation of microglia, are intensively addressed, because they are profoundly correlated with the generation of reactive oxygen species and changes in pro-/anti-inflammatory phenotypes.