Perspectives on Future Translational Research on Brain Edema

Advances in understanding the molecular mechanisms of cerebral edema formation are leading to a fundamental transition, away from the era of osmotherapeutics and steroids to an era of molecularly targeted therapies. Challenges remain. There is an active debate regarding the source(s) of edema fluid, with the classic theory involving endothelium now challenged by the novel concept of the glymphatic system. Future work will have to embrace new conditions, such as CAR-T cell therapies, in which cerebral edema can play a newly discovered, deadly role. The recent trial of RP-1127 showed that molecularly directed therapies can be remarkably effective, and revealed the previously unappreciated role of “RP-1127-insensitive” swelling, the molecular mechanism of which is unknown. Efforts to refine our mechanistic understanding of cerebral edema formation undoubtedly will be justified by the high likelihood that resulting insights will lead to novel treatments for a large variety of CNS conditions associated with edema formation.