An Ping, Zhao Xiao-Chun, Liu Man-Jia, You Yu-Qing, Li Jing-Ya, Gong He-Song
Department of Neurobiology, School of Life Science, China Medical University, Shenyang, China.
Department of Anesthesiology, School and Hospital of Stomatology, China Medical University, Shenyang, China.
Front Pharmacol. 2022 Apr 1;13:852401. doi: 10.3389/fphar.2022.852401. eCollection 2022.
Post-stroke anxiety severely affects recovery in patients with intracerebral hemorrhage (ICH). Dexmedetomidine (Dex), a highly selective alpha 2 adrenal receptor (α2-AR) agonist, was recently found to exert an excellent protective effect against mental disorders including anxiety. The transient receptor potential vanilloid 4 (TRPV4) channel is involved in a series of diseases such as asthma, cancer, anxiety, and cardiac hypertrophy. This study examines whether Dex improved ICH-induced anxiety via the inhibition of TRPV4 channel opening. A rodent model of moderate ICH in the basal ganglia was established using autologous blood injection (20 μl). Mice were treated with Dex (25 μg/kg, intraperitoneal injection) every day for 3 days post-ICH. GSK1016790A (1 μmol/2 μl), an agonist of TRPV4, was administered the left lateral ventricle. Thirty days post-ICH, post-stroke anxiety was evaluated by elevated plus-maze and open-field tests. Following behavioral tests, superoxide dismutase (SOD), malondialdehyde (MDA), astrocytic activation, and A1-and A2-type astrocytes were determined. Primary astrocytes were exposed to hemin to simulate ICH . Compared with sham-treated mice, Dex administration ameliorates ICH-induced decreases of distance and time in the open-arm, reduces distance and time in the central zone, increases astrocytic activation and A1-type astrocytes, elevates MDA content, downregulates total SOD contents, and decreases A2-type astrocytes. However, GSK1016790A partially reversed the neuroprotective effects of Dex. In addition, Dex significantly inhibited hemin-induced astrocytic activation . Dex improves ICH-induced anxiety-like behaviors in mice, and the mechanism might be associated with the inhibition of TRPV4-channel opening.
脑出血（ICH）后焦虑严重影响患者的康复。右美托咪定（Dex）是一种高选择性α2肾上腺素能受体（α2-AR）激动剂，最近发现其对包括焦虑在内的精神障碍具有出色的保护作用。瞬时受体电位香草酸受体4（TRPV4）通道参与了一系列疾病，如哮喘、癌症、焦虑和心肌肥大。本研究探讨Dex是否通过抑制TRPV4通道开放来改善ICH诱导的焦虑。采用自体血注射（20 μl）建立基底节区中度ICH的啮齿动物模型。ICH后连续3天每天给小鼠腹腔注射Dex（25 μg/kg）。将TRPV4激动剂GSK1016790A（1 μmol/2 μl）注入左侧脑室。ICH后30天，通过高架十字迷宫和旷场试验评估中风后焦虑。行为测试后，测定超氧化物歧化酶（SOD）、丙二醛（MDA）、星形胶质细胞活化以及A1型和A2型星形胶质细胞。原代星形胶质细胞暴露于血红素以模拟ICH。与假手术组小鼠相比，给予Dex可改善ICH诱导的在开放臂中的距离和时间减少，减少在中央区域的距离和时间，增加星形胶质细胞活化和A1型星形胶质细胞，提高MDA含量，下调总SOD含量，并减少A2型星形胶质细胞。然而，GSK1016790A部分逆转了Dex的神经保护作用。此外，Dex显著抑制血红素诱导的星形胶质细胞活化。Dex改善小鼠ICH诱导的焦虑样行为，其机制可能与抑制TRPV4通道开放有关。
