Exosomes in Traumatic Brain Injury: From Secondary Injury Mechanisms to Cell-Free Neurorepair.

Abstract

Traumatic brain injury (TBI) is a leading cause of death and long-term neurological disability worldwide. Exosomes (EXOs) have attracted increasing attention because they mediate intercellular communication and show promise as diagnostic biomarkers and cell-free therapeutics. However, the overall research landscape and evolving priorities of exosomes studies in TBI remain insufficiently characterized. We performed a bibliometric analysis of publications indexed in the Web of Science Core Collection (WoSCC) and Scopus (search date: October 24, 2025) using equivalent search strategies combining traumatic brain injury and exosome/extracellular vesicle terms. English-language original research and review articles published between January 1, 2012 and October 24, 2025 were eligible; editorials, letters, conference abstracts, and non-English publications were excluded. After deduplication and screening, 609 publications were retained. A multi-tool analytical framework was employed: CiteSpace (v6.4.R1) for citation-burst detection, co-occurrence clustering, and timeline visualization; VOSviewer (v1.6.18) for collaboration network mapping and keyword co-occurrence analysis; and the Bibliometrix R package (v4.4.3) for descriptive statistics, productivity indicators (h-index, g-index, m-index), and performance metrics. From 2012 to 2025, research on exosomes in TBI expanded steadily, with accelerated growth after 2017. Keyword co-occurrence, citation-burst detection, and reference co-citation analyses showed a clear thematic evolution. Early studies and highly co-cited references primarily addressed secondary-injury mechanisms, particularly neuroinflammation, microglial activation, glial-neuronal interactions, and blood-brain barrier dysfunction. Influential work by frequently co-cited authors (e.g., Chopp M and Zhang Y) helped establish exosomes-mediated neuroprotection and neurovascular remodeling as central themes. More recently, burst keywords and emerging co-citation clusters have shifted toward mesenchymal stem cell-derived exosomes, cell-free therapeutic strategies, engineered exosomes, drug delivery systems, and regenerative medicine, reflecting a transition from mechanistic exploration to translational application. This shift has coincided with the growing prominence of journals such as the International Journal of Molecular Sciences, Journal of Neurotrauma, Cells, and Neural Regeneration Research as major publication venues for the field. This study maps the global landscape of exosomes research in TBI and traces its evolution from pathogenesis to regenerative therapy. The United States and China stand out as complementary leaders, with American groups focusing on mechanisms and biomarkers and Chinese groups driving therapeutic translation. Future priorities for clinical translation include standardized isolation protocols, optimal dosing regimens, and rigorous clinical trials. Together, these findings offer a practical framework to guide the development of exosome-based therapies for TBI.