# Serum P2X7 as a prognostic biomarker in acute supratentorial intracerebral hemorrhage: a two-center observational study

## TL;DR

This study shows that high levels of serum P2X7 in patients with brain hemorrhage are linked to worse outcomes and could help predict prognosis.

## Contribution

The study identifies serum P2X7 as a novel prognostic biomarker for acute supratentorial intracerebral hemorrhage.

## Key findings

- Serum P2X7 levels peak at day 3 after hemorrhage and remain elevated compared to controls.
- Higher P2X7 levels correlate with worse NIHSS scores, hematoma volume, and poor 6-month outcomes.
- A combined model of P2X7, NIHSS, and hematoma volume improves prognostic accuracy.

## Abstract

P2X7 participates in neuroinflammation underlying acute brain injury. In this study, we investigated the prognostic role of serum P2X7 in acute intracerebral hemorrhage (ICH).

This two-center observational analytic study enrolled 95 controls and 196 patients with acute supratentorial ICH. Serum P2X7 levels were measured at study entry in controls and at admission in all ICH patients, with serial measurements performed in a subgroup of 95 patients. Disease severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. The primary neurological functional outcome was assessed using the modified Rankin Scale (mRS) at 6 months post-ICH. Multivariable analysis was performed to model the associations between P2X7 levels, disease severity, and final functional prognosis.

In patients with ICH, serum P2X7 levels were markedly elevated upon admission, peaked at day 3, and gradually declined through to day 10. Patient serum P2X7 levels remained notably higher than those of controls throughout the 10-day period. Serum P2X7 levels were linearly correlated with NIHSS scores, hematoma volume, mRS scores, and poor prognosis (mRS 3–6) under restricted cubic spline analysis. These associations persisted after adjustment for potential confounding factors. Sensitivity analyses, subgroup analyses, and receiver operating characteristic (ROC) curve analysis consistently demonstrated that serum P2X7 levels were robustly associated with poor prognosis. Applying calibration curve, decision curve, ROC curve, and model improvement rate analyses, a combined model integrating serum P2X7 levels, NIHSS scores, and hematoma volume demonstrated strong performance. Furthermore, serum P2X7 levels partially mediated the correlations of NIHSS scores and hematoma volume with poor prognosis.

Increased serum P2X7 levels after ICH are markedly associated with disease severity and poor prognosis. Moreover, P2X7 may partially mediate the relationship between ICH severity and prognosis, underscoring its potential as a prognostic biomarker.