Neonatal hypoxic-ischemic encephalopathy (HIE) is an obstinate disease that troubles neonatologists. At present, cognitive impairment after HIE has received increasing attention. Synaptic plasticity determines the development of cognitive function, so it is urgent to develop new drugs that can improve HIE-induced cognitive impairment. Hypoxia–ischemia (HI)–induced neuroinflammation affects synaptic plasticity. As a SIRT1 agonist, resveratrol has a powerful anti-inflammatory effect, but whether it has an effect on impaired synaptic plasticity in HIE and the potential mechanism remain unclear. In the present study, resveratrol was used to intervene in hypoxic-ischemic brain injury (HIBI) mice, and the effects on hippocampal synaptic plasticity and further mechanisms were explored through performing neurobehavioral, morphological observations, Golgi sliver staining, western blotting, and quantitative real-time polymerase chain reaction experiments. We first found that resveratrol improves HI-induced long-term cognitive and memory deficits, and then we found that resveratrol reduces hippocampal neuronal damage and increases dendritic spine density and the expression of synaptic proteins. Finally, we found that this effect may be exerted by regulating the neuroinflammatory response mediated by the SIRT1/NF-κB axis. This study provides a new theoretical basis for resveratrol to prevent long-term neurological dysfunction following HIBI.

新生儿缺氧缺血性脑病 (HIE) 是一种困扰新生儿科医生的顽固疾病。目前，HIE后的认知障碍越来越受到重视。突触可塑性决定了认知功能的发展，因此迫切需要开发能够改善HIE引起的认知障碍的新药。缺氧缺血（HI）诱导的神经炎症影响突触可塑性。作为 SIRT1 激动剂，白藜芦醇具有强大的抗炎作用，但它是否对 HIE 中受损的突触可塑性有影响及其潜在机制尚不清楚。在本研究中，白藜芦醇用于干预缺氧缺血性脑损伤 (HIBI) 小鼠，通过神经行为学、形态学观察，探索其对海马突触可塑性的影响和进一步机制，高尔基体染色、蛋白质印迹和定量实时聚合酶链反应实验。我们首先发现白藜芦醇改善 HI 诱导的长期认知和记忆缺陷，然后我们发现白藜芦醇减少海马神经元损伤并增加树突棘密度和突触蛋白的表达。最后，我们发现这种效应可能是通过调节由 SIRT1/NF-κB 轴介导的神经炎症反应来发挥的。该研究为白藜芦醇预防HIBI后长期神经功能障碍提供了新的理论基础。然后我们发现白藜芦醇减少海马神经元损伤并增加树突棘密度和突触蛋白的表达。最后，我们发现这种效应可能是通过调节由 SIRT1/NF-κB 轴介导的神经炎症反应来发挥的。该研究为白藜芦醇预防HIBI后长期神经功能障碍提供了新的理论基础。然后我们发现白藜芦醇减少海马神经元损伤并增加树突棘密度和突触蛋白的表达。最后，我们发现这种效应可能是通过调节由 SIRT1/NF-κB 轴介导的神经炎症反应来发挥的。该研究为白藜芦醇预防HIBI后长期神经功能障碍提供了新的理论基础。