Extracellular Vesicles from Poor-Outcome Intracerebral Hemorrhage Patients Reveal Limited Reparative Potential in a Preclinical Model

Extracellular vesicles (EVs) have emerged as potential therapeutic agents for neurological disorders. Their molecular cargo may reflect the clinical status of the donor and has been identified as a biomarker for the cellular damage and repair processes underlying intracerebral hemorrhage (ICH). It has been shown that EVs from patients with favorable outcomes carry a distinct proteomic signature, compared to those from poor outcome patients, which may promote recovery in preclinical models of ICH. We investigated whether intravenously administered EVs isolated from patients with poor outcomes after ICH provide any benefit in a preclinical ICH model. No significant differences were observed in lesion volume between the placebo and treatment groups at 24 h, 72 h, or 28 days post-ICH. Functional assessments using the Rogers and tapered beam walking tests revealed no improvement in motor performance in the treatment group at 24 h, 72 h, 7 d, 14 d and 28 d. Histological analysis at 28 days showed no significant differences in immunofluorescence markers of myelin preservation (MOG, Olig-2), astroglial activation (GFAP), or angiogenesis (VEGF) between groups. In conclusion, EVs derived from patients with poor outcomes after ICH failed to promote functional recovery or modulate markers of injury and repair in a rat model, suggesting few endogenous repair mechanisms.