Cerebral edema and the glymphatic system in traumatic brain injury

Traumatic brain injury (TBI) is a significant public health concern, leading to considerable morbidity, mortality, and long-term disability across the globe. One of the major contributors to poor outcomes following TBI is cerebral edema, a secondary injury process characterized by excess accumulation of fluid in the brain parenchyma, which elevates intracranial pressure (ICP) and exacerbates neurological damage. Despite advances in the management of TBI, current therapies such as osmotherapy and decompressive craniectomy focus predominantly on controlling ICP rather than addressing the underlying mechanisms of edema. Emerging research highlights a crucial need to explore novel therapeutic strategies that directly target cerebral edema and its complex pathophysiology, as conventional approaches have not led to substantial improvements in patient outcomes.

Recent attention has turned to the glymphatic system, a brain-wide perivascular network that facilitates clearance of interstitial solutes and metabolic waste through coordinated cerebrospinal fluid (CSF) and interstitial fluid dynamics. Dysfunction of the glymphatic system has been implicated inbrain edema and secondary injury in TBI, with animal studies providing compelling evidence of its role in both acute and chronic phases of disease. However, translational data in human TBI patients remains sparse, and the dynamic function of CSF circulation in the parenchyma and ventricles after acute and chronic TBIs is yet to be fully characterized. Understanding these mechanisms may reveal novel targets for intervention and help bridge the gap between neurobiological insights and therapeutic innovation.

This Research Topic aims to advance knowledge of the glymphatic system’s role in mediating and modulating cerebral edema in TBI, thereby informing the development of precision interventions. By focusing on both experimental and clinical investigations, the objective is to elucidate how glymphatic dysfunction contributes to TBI-related edema, identify molecular and physiological pathways amenable to therapeutic modulation, and foster translational strategies to improve outcomes for patients with TBI.

To gather further insights into the boundaries and clinical relevance of glymphatic dysfunction in TBI, we welcome articles that address, but are not limited to, the following themes:

o Pathophysiological alterations in the glymphatic system following TBI in experimental and human studies

o Emerging technologies for in vivo assessment of glymphatic function in health and acute brain injury

o The relationship between noradrenergic signaling, glymphatic system impairment, and cerebral edema formation

o Interactions between glymphatic system activity, CSF dynamics, and acute versus chronic outcomes in TBI

o Novel molecular and interventional strategies to target the glymphatic system in the prevention or treatment of cerebral edema