S-Nitrosoglutathione as a Multifaceted Neurovascular Protector Against Reperfusion Injury in Hypoxic–Ischemic Encephalopathy

Objective: Reperfusion injury in hypoxic–ischemic encephalopathy (HIE) exacerbates neuronal and vascular damage through oxidative stress, vascular dysfunction, and cell death, necessitating therapeutic strategies targeting multiple pathological pathways. This study evaluates the neurovascular protective effects of S-nitrosoglutathione (GSNO) in a zebrafish model of hypoxia–reoxygenation injury. Hypothesis: We hypothesize that GSNO administration during early reoxygenation mitigates neuronal and vascular damage by modulating oxidative stress and cell death pathways. Methods: Zebrafish larvae were subjected to hypoxia–reoxygenation to model HIE-associated reperfusion injury. GSNO was administered at reoxygenation onset, and its effects on survival, motor function, and neurovascular integrity were assessed. Markers of oxidative stress and cell death, including apoptotic and ferroptotic pathways, were analyzed to elucidate underlying mechanisms. Results: GSNO treatment enhanced survival and behavioral recovery in a dose-dependent manner. It preserved neurovascular function and reduced markers of oxidative stress and cell death, suggesting a multifaceted protective mechanism. Conclusions: These findings highlight GSNO as a potential therapeutic candidate for mitigating reperfusion injury in HIE. Its neurovascular protection appears to involve vasodilation, redox modulation, and inhibition of apoptotic and ferroptotic pathways. The zebrafish model provides a valuable platform for studying HIE pathophysiology and evaluating therapeutic interventions. Further studies are warranted to explore translational applications. National Science and Technology Council, Taiwan (111-2113-M-A49-020-MY3 and 113-2811-M-A49-553) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.