Plasma transfusion therapy enhances recovery from traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of disability and death worldwide. Despite its significant impact, effective treatments for TBI remain limited, and the resulting damage is largely irreversible. Recently, plasma or whole blood transfusion has been demonstrated to enhance neurogenesis, improve cognitive outcomes, and even promote the recovery from ischemic brain injury in mice. Based on these findings, this study aims to investigate whether plasma transfusion also offers benefits in the recovery process following TBI. Our results demonstrate that intravenous plasma transfusion in TBI mice significantly improves sensorimotor functions, reduces perilesional cell death, and preserves axonal projections. Global LC-MS/MS proteomics of the injured cortex further revealed ferroptosis signaling as the most significantly altered pathway, according to Ingenuity Pathway Analysis. Furthermore, different sources of plasma exert varying therapeutic effects, with young plasma, rather than aged or TBI-derived plasma, leading to the most remarkable behavioral improvement. Comparative proteomics analysis of young, aged, and TBI plasma identified thirteen candidate proteins that may be involved in these therapeutic effects. Overall, these findings indicate that plasma transfusion, especially from young healthy donors, improves functional outcomes and alleviates structural brain damage, offering a potential therapeutic strategy for TBI.