| Cerebral edema is the most common intracranial emergency in China,and is particularly common in cerebral ischemia and traumatic brain injury.The timing of treatment of cerebral edema has a major impact on the recovery of neurological function,and also related to the high mortality and high morbidity.The clinical treatment of cerebral edema is mainly limited to hypertonic therapy,and the anti-cerebral edema drugs currently used have certain limitations.The detailed mechanism of brain edema is not well understood,which limits the development of new anti-cerebral edema drugs.Due to cerebral edema caused by cerebral ischemia and brain trauma,necrotic cells are distributed in and around the injured area where necrosis is the main pathological change.The key molecules in these necrotic cells and their necrosis procedures may participate in the cerebral edema process.Aquaporin is an important protein involved in the process of cerebral edema.It is distributed in astrocytes.It regulates the water component in the brain and participates in the formation of cerebral edema on the one hand.It also participates in the absorption and transfer of excess water in the brain on the other hand.Therefore,investigating the relationship between cerebral ischemia and cellular necrosis and the expression of aquaporin may provide new ideas for the research and treatment of cerebral edema.Objective:To study the expression and role of mixed lineage domain-like protein(MLKL)and RIP3,two key molecules in necroptosis in brain edema of C57BL/6J mice,and to provide new ideas for the mechanistic research and treatment of brain edema.Materials and Methods: Focal cerebral ischemia was made by photothrombosis.Brain trauma was made by a computer controlled impactor.Brain tissues were collected at 3 d or 1week after brain injury.Immunohistochemistry,Western Blot,immune-electron microscopic methods and HE staining were conducted to explore the roles of MLKL and RIP3 in brain injury-induced edema.Results: The expression of MLKL and RIP3 are up-regulated in the injured cortex of both cerebral ischemia and CCI model.In normal cerebral cortex,there is no or very weakexpression of MLKL and RIP3.In the injured cortex,during edema phase,MLKL and RIP3 are mainly expressed by the para-aortic astrocytes.Depletion of MLKL and RIP3 could significantly reduce the area of edema,inhibit the extravascular accumulation of IgG,and increase the expression of aquaporin-4,suggesting that MLKL and RIP3 may be involved in the regulation of cerebral edema,which may serve as a new target for the study of cerebral edema.Conclusion: The expression of MLKL and RIP3 are up-regulated in the para-aortic astrocytes in the injured cortex with cerebral edema.Mutation of MLKL or RIP3 can alleviate injury-induced brain edema. |
