Subarachnoid hemorrhage (SAH) is a catastrophic form of stroke responsible for significant morbidity and mortality. Oxidative stress, inflammation, and neuronal apoptosis are important in the pathogenesis of early brain injury (EBI) following SAH. Preconditioning exercise confers neuroprotective effects, mitigating EBI; however, the basis for such protection is unknown. We investigated the effects of preconditioning exercise on brain damage and sensorimotor function after SAH. Male rats were assigned to either a sham-operated (Sham) group, exercise (Ex) group, or no-exercise (No-Ex) group. After a 3-week exercise program, they underwent SAH by endovascular perforation. Consciousness level, neurological score, and sensorimotor function were studied. The expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), 4-hydroxynonenal (4HNE), nitrotyrosine (NT), ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), 14–3-3γ, p-β-catenin Ser37, Bax, and caspase-3 were evaluated by immunohistochemistry or western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL) assay was also performed. After SAH, the Ex group had significantly reduced neurological deficits, sensorimotor dysfunction, and consciousness disorder compared with the No-Ex group. Nrf2, HO-1, and 14–3-3γ were significantly higher in the Ex group, while 4HNE, NT, Iba1, TNF-α, IL-6, IL-1β, Bax, caspase-3, and TUNEL-positive cells were significantly lower. Our findings suggest that preconditioning exercise ameliorates EBI after SAH. The expression of 4HNE and NT was reduced by Nrf2/HO-1 pathway activation; additionally, both oxidative stress and inflammation were reduced. Furthermore, preconditioning exercise reduced apoptosis, likely via the 14–3-3γ/p-β-catenin Ser37/Bax/caspase-3 pathway.

蛛网膜下腔出血 (SAH) 是一种灾难性的中风形式，可导致显着的发病率和死亡率。氧化应激、炎症和神经元凋亡在 SAH 后早期脑损伤 (EBI) 的发病机制中很重要。预处理运动赋予神经保护作用，减轻 EBI；然而，这种保护的依据是未知的。我们研究了预处理运动对 SAH 后脑损伤和感觉运动功能的影响。雄性大鼠被分配到假手术 (Sham) 组、运动 (Ex) 组或不运动 (No-Ex) 组。经过 3 周的锻炼计划后，他们通过血管内穿孔接受了 SAH。研究了意识水平、神经学评分和感觉运动功能。核因子红细胞 2 p45 相关因子 2 (Nrf2)、血红素加氧酶 1 (HO-1) 的表达，p-β-连环蛋白 Ser37、Bax 和 caspase-3 通过免疫组织化学或蛋白质印迹进行评估。还进行了末端脱氧核苷酸转移酶介导的生物素化 dUTP 缺口末端标记 (TUNEL) 测定。SAH 后，与未前组相比，前组的神经功能缺损、感觉运动功能障碍和意识障碍显着降低。Ex 组的 Nrf2、HO-1 和 14-3-3γ 显着升高，而 4HNE、NT、Iba1、TNF-α、IL-6、IL-1β、Bax、caspase-3 和 TUNEL 阳性细胞显着降低。我们的研究结果表明，预处理运动可以改善 SAH 后的 EBI。Nrf2/HO-1通路激活降低了4HNE和NT的表达；此外，氧化应激和炎症都减少了。此外，预处理运动减少了细胞凋亡，可能通过 14-3-3γ/p -β-连环蛋白 Ser37/Bax/caspase-3 通路。