Neuroprotective Effects of Quercetin in Neonatal Hypoxic-Ischemic Brain Injury: A Meta-analysis

Abstract

Objective

This study assesses the neuroprotective potential of quercetin in preclinical models of neonatal hypoxic-ischemic brain injury (HIBI) and its role as a possible enhancer of therapeutic hypothermia.

Study Design

A systematic review of 8 preclinical studies was conducted per PRISMA guidelines, sourced from PubMed, Scopus, and Web of Science, with a random-effects meta-analysis.

Results

Quercetin significantly lowered infarct volume, seizure susceptibility, and inflammation (pooled standardized mean differences [SMD] = 1.29; 95% confidence interval [CI]: 1.00–1.58; p < 0.001). Higher doses (>30 mg/kg, SMD = 1.65) and intraperitoneal (IP) administration (SMD = 1.42) outperformed lower doses or intravenous (IV) routes (SMD = 0.95). Rat models showed greater benefits (SMD = 1.38) than piglets (SMD = 0.85). Moderate heterogeneity (I ² = 45%) was noted, but sensitivity analysis confirmed robustness (SMD = 1.20). Publication bias was minimal (p = 0.12).

Conclusion

Quercetin offers notable neuroprotection in neonatal HIBI, with an optimal 40 mg/kg IP dose, suggesting it could complement hypothermia. Limited bioavailability and lack of long-term data call for further research in advanced models.

Key Points

• Quercetin improves outcomes in neonatal HIBI.

• IP route shows greater efficacy.

• Higher doses (>30 mg/kg) are more effective.

• Meta-analysis confirms significant benefit (SMD = 1.29).

• Bioavailability remains a key translational barrier.

Keywords

quercetin - neonatal hypoxic-ischemic brain injury - neuroprotection - meta-analysis - therapeutic hypothermia

Publication History

Received: 21 February 2025

Accepted: 08 April 2025

Article published online:
30 April 2025

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