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Investigating the neuroprotective effect of heparin in improving mitochondrial function in rats with cardiac arrest cardiopulmonary resuscitation based on transcriptome sequencing

Year: 2026

Type: article

Abstract: Background: Cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR) often lead to severe brain injury, primarily driven by mitochondrial dysfunction and ischemia-reperfusion injury. While heparin is a known anticoagulant, its potential neuroprotective role through mitochondrial regulation post cardiac arrest and cardiopulmonary resuscitation (CA-CPR) remains poorly understood. This study aimed to explore the brain-protective mechanisms of heparin, focusing on its effects on mitochondrial function using transcriptome sequencing in a rat model of asphyxial CA-CPR. Methods: Male Sprague-Dawley rats were randomized into three groups: Sham, CPR (Model), and CPR + Heparin (CPR + HP, 0.5 mg/kg IV upon CPR initiation). Neurological function was assessed using modified Neurological Severity Scores (mNSS) over 7 days. Hippocampal tissues were collected for transcriptome sequencing, qPCR validation, histological examination (HE staining), transmission electron microscopy (TEM), and biochemical assays (ATP and ROS levels). Bioinformatic analyses included differential gene expression, KEGG/GO enrichment, protein-protein interaction (PPI) networks, and ROC analysis. Results: < 0.05). ROC analysis confirmed their diagnostic value (AUC > 0.75). Heparin also increased ATP content, reduced ROS levels, and preserved neuronal and mitochondrial ultrastructure. Conclusion: Heparin provided neuroprotection after CA-CPR by ameliorating mitochondrial dysfunction via multi-target regulation of key genes (Epsa1, Idh2, and Hif3a), enhancing energy metabolism, reducing oxidative stress, and inhibiting hyperactivated coagulation-inflammation cascades. These findings highlight heparin's potential as an adjunctive therapy for improving neurological outcomes post-resuscitation.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2025.1712265