Single atom-substituted gold nanoclusters for alleviating neural injury induced by deep hypothermic circulatory arrest.

BACKGROUND: Neurological deficit is a common complication of deep hypothermic circulatory arrest (DHCA). Among the diverse factors contributing to neural injury, oxidative stress plays a prominent role. Emerging nanocluster technology has demonstrated considerable antioxidant and anti-inflammation activity. In this study, we developed a novel type of nanocluster for the treatment of neural injury induced by DHCA. METHODS: Single atom-substituted gold nanoclusters (AuNCs) were synthesized. PC-12 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) and a rat DHCA model were employed. Cell viability was evaluated via Cell Counting Kit-8 (CCK-8). Histopathological changes in the hippocampus were evaluated by hematoxylin-eosin staining. S100 calcium-binding protein β (S100β), neuron-specific enolase (NSE), malondialdehyde (MDA), and interleukin-1β (IL-1β) levels were determined by enzyme-linked immunosorbent assay (ELISA). Expression of S100β, caspase-3, and cleaved caspase-3 was assessed via Western blotting. RESULTS: AuNCs exhibited strong antioxidant capacities, mimicking superoxide dismutase (SOD) and catalase (CAT) activities. In vitro studies demonstrated improved neuronal survival following OGD/R. In vivo, DHCA-induced hippocampal damage was significantly alleviated by AuNCs treatment, as evidenced by reduced histological neuronal degeneration, decreased levels of inflammatory cytokines (TNF-α and IL-1β), and downregulation of apoptotic markers (caspase-3 and cleaved caspase-3). CONCLUSIONS: The newly developed AuNCs alleviated the neural injury induced by DHCA through anti-inflammation, antioxidant, and anti-apoptosis activity. These findings offer a novel avenue for achieving perioperative brain protection in clinical DHCA and provide a new direction for developing catalysts in medical applications.