ABSTRACT NUMBER: ESOC2026A1128 THE ROLE AND MECHANISM OF COX7C IN REGULATING MITOCHONDRIAL MEDIATED NEURONAL APOPTOSIS IN CEREBRAL ISCHEMIA-REPERFUSION INJURY

Abstract Background and aims Acute ischemic stroke is a major disease which causes death and disability in humans. Mitochondrial dysfunction plays a critical role in the mechanism of cerebral ischemia-reperfusion injury (CIRI). Cytochrome C Oxidase Subunit 7C (Cox7c) is a key factor in maintaining mitochondrial function, and its functional deficiency is closely related to neurological and metabolic diseases. However, its specific role and regulatory mechanism in CIRI remain unclear. Methods In vivo and in vitro CIRI models were established using mouse transient middle cerebral artery occlusion (tMCAO) and neuronal oxygen-glucose deprivation/reoxygenation (OGD/R), respectively. Neuronal-targeted adeno-associated virus (AAV) and lentiviruses (LV) overexpressing Cox7c were constructed. Neurological dysfunction was assessed via mNSS scoring, beam walking test, and corner test. Cerebral infarct volume was evaluated using TTC staining. Cerebral blood flow was monitored through laser speckle imaging. Neuronal survival and pathological morphology were observed by Nissl and HE staining. Mitochondrial function alterations were detected through ROS, ATP, and JC-1 assays. Apoptotic bodies were labelled using TUNEL staining. Apoptosis-related proteins and pathway-related proteins were detected by Western Blot. RNA-seq identified significantly enriched signaling pathways associated with Cox7c regulation. Results After CIRI, Cox7c expression was markedly reduced in neurons in the ischemic penumbra region. Cox7c overexpression significantly improved neurological function and reduced infarct volume Furthermore, Cox7c overexpression substantially mitigated mitochondrial dysfunction and apoptosis. RNA-seq revealed that TNF-α signaling pathway was markedly suppressed. Conclusions Cox7c over expression could improve mitochondrial function and inhibit neuronal apoptosis after CIRI. This protective effect was achieved through the suppression of the TNF-α signaling pathway. Conflict of interest Name of author: nothing to disclose