Mapping the Landscape of Diaschisis in Traumatic Brain Injury: A Scoping Review.

Diaschisis is a phenomenon in which damage to one brain region leads to dysfunction in remote, yet functionally connected, areas. Although it has been well characterized in stroke, the complex, multifocal nature of traumatic brain injury (TBI) suggests that similar network-level disruptions could occur, yet the presence and impact of diaschisis in TBI remain underexplored. This gap may stem from a historical focus on cerebrovascular events, underrecognition of diaschisis in TBI, and methodological challenges related to TBI's heterogeneous nature. This review maps diaschisis in TBI by examining models, mechanisms, neuroimaging, clinical features, and therapeutic interventions. A PRISMA-ScR guided search of PubMed, Embase, and Cochrane included studies explicitly addressing diaschisis in TBI from inception up to January 2025. Two independent reviewers screened titles, abstracts, and full texts, with discrepancies resolved by consensus. Twenty-three studies were included, encompassing 110 human participants, 497 animals, and one in vitro model. Among these, 57% used neuroimaging, 39% assessed functional outcomes, and 22% examined potential interventions. The predominant experimental model was rodent-controlled cortical impact, typically simulating moderate TBI. Contrarily, human studies were fewer and focused on severe TBI cases. Crossed cerebellar diaschisis was the most common neuroimaging finding (36%), with MRI used most frequently, followed by PET and SPECT. Across both clinical studies and preclinical models, key mechanisms of diaschisis included deafferentation, reduced metabolism, altered glutamate signaling, hypoperfusion, and distant apoptotic cell death. Motor deficits were more common with better recovery than cognitive impairments. Interventions such as MK-801 and Ifenprodil showed potential to reverse diaschisis, but others had limited effects. This review underscores the limited but growing understanding of diaschisis in TBI. Targeted research on mild-to-moderate TBI, interventions, and imaging-validation trials is needed to improve diagnosis and treatment.