The Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha, 410000, China; Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, Changsha Medical University, Changsha, 410000, China.
The Hunan Provincial University Key Laboratory of the Fundamental and Clinical Research on Functional Nucleic Acid, Changsha Medical University, Changsha, 410000, China; Wuzhou Medical College, Wuzhou, 543199, China.
Eur J Pharmacol. 2023 Jul 15;951:175801. doi: 10.1016/j.ejphar.2023.175801. Epub 2023 May 18.
DL-3-n-butylphthalide (NBP) and edaravone dexborneol (Eda-Dex) are two promising reagents for stroke treatment. However, the impacts of NBP and Eda-Dex on poststroke mental deficits are still poorly understood. In this study, we aimed to investigate and compare the influences of NBP and Eda-Dex on neurological function and cognitive behavior in rats with ischemic stroke.
An ischemic stroke model was established by middle cerebral artery occlusion (MCAO). After peritoneal administration of the drugs, the rats were subjected to neurological deficit evaluation, cerebral blood flow (CBF) assays, cerebral infarct area evaluations or behavioral tests. Brain tissues were collected and further analyzed by enzyme-linked immunosorbent assay (ELISA), western blotting or immunohistochemistry.
NBP and Eda-Dex significantly decreased the neurological score, reduced the cerebral infarct area and improved CBF. Behavioral changes as assessed in the sucrose preference test, novel object recognition test, and social interaction test were significantly alleviated by NBP and Eda-Dex in rats with ischemic stroke. Moreover, NBP and Eda-Dex significantly suppressed inflammation by targeting the nuclear factor kappa-B/inducible nitric oxide synthase (NF-κB/iNOS) pathway and significantly inhibited oxidative stress by targeting the kelch-1ike ECH-associated protein l/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway. In addition, NBP and Eda-Dex distinctly suppressed the activation of microglia and astrocytes and improved neuronal viability in the ischemic brain.
NBP and Eda-Dex improved neurological function and alleviated cognitive disorders in rats with ischemic stroke by synergistically inhibiting inflammation and oxidative stress.
DL-3-正丁基苯酞(NBP)和依达拉奉右莰醇(Eda-Dex)是两种有前途的脑卒中治疗试剂。然而,NBP 和 Eda-Dex 对脑卒中后精神缺陷的影响仍知之甚少。在本研究中,我们旨在研究和比较 NBP 和 Eda-Dex 对缺血性脑卒中大鼠神经功能和认知行为的影响。
通过大脑中动脉闭塞(MCAO)建立缺血性脑卒中模型。药物腹腔给药后,对大鼠进行神经功能缺损评分、脑血流(CBF)测定、脑梗死面积评估或行为学测试。收集脑组织,通过酶联免疫吸附试验(ELISA)、蛋白质印迹或免疫组织化学进一步分析。
NBP 和 Eda-Dex 显著降低神经评分,减少脑梗死面积,改善 CBF。NBP 和 Eda-Dex 可显著改善缺血性脑卒中大鼠蔗糖偏好试验、新物体识别试验和社交互动试验中的行为变化。此外,NBP 和 Eda-Dex 通过靶向核因子κB/诱导型一氧化氮合酶(NF-κB/iNOS)通路显著抑制炎症,通过靶向 Kelch-like ECH-associated protein l/nuclear factor erythroid 2-related factor 2(Keap1/Nrf2)通路显著抑制氧化应激。此外,NBP 和 Eda-Dex 明显抑制缺血大脑中小胶质细胞和星形胶质细胞的激活,并提高神经元活力。
NBP 和 Eda-Dex 通过协同抑制炎症和氧化应激,改善缺血性脑卒中大鼠的神经功能,减轻认知障碍。