Background. Brain injury is the leading cause of death following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Ac2-26 and endothelial nitric oxide synthase (eNOS) have been shown to reduce neuroinflammation. This study is aimed at determining the mechanism by which Ac2-26 protects against inflammation during brain injury following CA and CPR. Methods. Sixty-four rats were randomized into sham, saline, Ac2-26, and Ac2-26+L-NIO (endothelial nitric oxide synthase (eNOS) inhibitor) groups. Rats received Ac2-26, Ac2-26+L-NIO, or saline after CPR. Neurologic function was assessed at baseline, 24, and 72 hours after CPR. At 72 hours after resuscitation, serum and brain tissues were collected. Results. Blood-brain barrier (BBB) permeability increased, and the number of surviving neurons and neurological function decreased in the saline group compared to the sham group. Anti-inflammatory and proinflammatory factors, neuron-specific enolase (NSE) levels, and the expression of eNOS, phosphorylated (p)-eNOS, inducible nitric oxide synthase (iNOS), and oxidative stress-related factors in the three CA groups significantly increased (). BBB permeability decreased, and the number of surviving neurons and neurological function increased in the Ac2-26 group compared to the saline group (). Ac2-26 increased anti-inflammatory and reduced proinflammatory markers, raised NSE levels, increased the expression of eNOS and p-eNOS, and reduced the expression of iNOS and oxidative stress-related factors compared to the saline group (). The effect of Ac2-26 on brain injury was reversed by L-NIO (). Conclusions. Ac2-26 reduced brain injury after CPR by inhibiting oxidative stress and neuroinflammation and protecting the BBB. The therapeutic effect of Ac2-26 on brain injury was largely dependent on the eNOS pathway.

中文翻译：

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Ac2-26 通过 eNOS 通路减轻大鼠心脏骤停和心肺复苏后的脑损伤。

背景。脑损伤是心脏骤停 (CA) 和心肺复苏 (CPR) 后死亡的主要原因。Ac2-26 和内皮一氧化氮合酶 (eNOS) 已被证明可以减少神经炎症。本研究旨在确定 Ac2-26 在 CA 和 CPR 后脑损伤期间防止炎症的机制。方法。将 64 只大鼠随机分为假手术组、盐水组、Ac2-26 组和 Ac2-26+L-NIO（内皮一氧化氮合酶 (eNOS) 抑制剂）组。大鼠在 CPR 后接受 Ac2-26、Ac2-26+L-NIO 或盐水。在 CPR 后的基线、24 和 72 小时评估神经功能。复苏后72小时，收集血清和脑组织。结果. 与假手术组相比，盐水组的血脑屏障 (BBB) 通透性增加，存活的神经元数量和神经功能下降。三个 CA 组的抗炎和促炎因子、神经元特异性烯醇化酶 (NSE) 水平以及 eNOS、磷酸化 (p)-eNOS、诱导型一氧化氮合酶 (iNOS) 和氧化应激相关因子的表达显着增加(）。与生理盐水组相比，Ac2-26 组 BBB 通透性降低，存活神经元数量和神经功能增加。）。与生理盐水组相比，Ac2-26 增加抗炎和减少促炎标志物，提高 NSE 水平，增加 eNOS 和 p-eNOS 的表达，降低 iNOS 和氧化应激相关因子的表达。）。Ac2-26 对脑损伤的作用被 L-NIO 逆转（）。 结论。Ac2-26 通过抑制氧化应激和神经炎症以及保护 BBB 来减轻 CPR 后的脑损伤。Ac2-26 对脑损伤的治疗作用很大程度上依赖于 eNOS 通路。