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

## TL;DR

EVs from ICH patients with poor outcomes do not help recovery in a rat model, suggesting limited repair potential.

## Contribution

Demonstrates that EVs from poor-outcome ICH patients lack therapeutic benefit in preclinical models.

## Key findings

- No significant differences in lesion volume were observed between placebo and treatment groups.
- Motor performance and histological markers showed no improvement in the treatment group.
- EVs from poor-outcome patients failed to modulate injury and repair markers in rats.

## Abstract

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.