Ischemic stroke is a neurological disease that causes brain damage by increasing oxidative stress and ion imbalance. Retinoic acid is a major metabolite of vitamin A and regulates oxidative stress, calcium homeostasis, and cell death. Intracellular calcium is involved in neuronal growth and synaptic plasticity. Parvalbumin is a calcium-binding protein that is mainly expressed in brain. In this study, we investigated whether retinoic acid has neuroprotective effects by controlling intracellular calcium concentration and parvalbumin expression in ischemic brain damage. Middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemia. Retinoic acid (5 mg/kg) or vehicle was injected into the abdominal cavity for four days before surgery and cerebral cortices were collected 24 h after MCAO for further studies. MCAO damage induced neurological deficits and histopathological changes and decreased parvalbumin expression. However, retinoic acid treatment alleviated these changes. In cultured neurons, glutamate (5 mM) exposure induced neuronal cell death, increased intracellular calcium concentration, and decreased parvalbumin expression. Retinoic acid treatment attenuated these changes against glutamate toxicity in a dose-dependent manner. It also regulates glutamate induced change in bcl-2 and bax expression. The mitigation effects of retinoic acid were greater under non-transfection conditions than under parvalbumin siRNA transfection conditions. Our findings showed that retinoic acid modulates intracellular calcium concentration and parvalbumin expression and prevents apoptosis in ischemic brain injury. In conclusion, retinoic acid contributes to the preservation of neurons from ischemic stroke by controlling parvalbumin expression and apoptosis-related proteins.

缺血性中风是一种神经系统疾病，通过增加氧化应激和离子失衡导致脑损伤。视黄酸是维生素 A 的主要代谢物，可调节氧化应激、钙稳态和细胞死亡。细胞内钙参与神经元生长和突触可塑性。Parvalbumin 是一种主要在脑中表达的钙结合蛋白。在这项研究中，我们通过控制缺血性脑损伤中的细胞内钙浓度和小白蛋白表达来研究视黄酸是否具有神经保护作用。进行大脑中动脉闭塞（MCAO）以诱导脑缺血。在手术前四天将视黄酸（5 mg/kg）或载体注射到腹腔中，并在 MCAO 后 24 小时收集大脑皮质用于进一步研究。MCAO 损伤引起神经功能缺损和组织病理学变化，并降低小白蛋白表达。然而，视黄酸处理减轻了这些变化。在培养的神经元中，谷氨酸 (5 mM) 暴露会诱导神经元细胞死亡、细胞内钙浓度增加和小清蛋白表达降低。视黄酸处理以剂量依赖的方式减弱了这些针对谷氨酸毒性的变化。它还调节谷氨酸诱导的 bcl-2 和 bax 表达变化。视黄酸的缓解作用在非转染条件下比在小清蛋白 siRNA 转染条件下更大。我们的研究结果表明，视黄酸可调节细胞内钙浓度和小白蛋白表达，并防止缺血性脑损伤中的细胞凋亡。综上所述，