Diaz Diaz Andrea C, Shearer Jennifer A, Malone Kyle, Waeber Christian
School of Pharmacy, University College Cork, Cork, Ireland.
Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland.
Front Pharmacol. 2021 Jan 8;11:613103. doi: 10.3389/fphar.2020.613103. eCollection 2020.
Intracerebral haemorrhage (ICH) has no specific treatment, but accounts for up to 15% of all strokes and has the highest mortality. Fingolimod (FTY720) is an immunomodulator approved for the management of multiple sclerosis, with abundant evidence of efficacy in experimental ischemic stroke, and more limited evidence in experimental ICH. The goal of this study was to confirm the efficacy of fingolimod in experimental ICH using rigorous and statistically well-powered studies. ICH was induced in C57BL/6JOlaHsd male and female mice by intrastriatal bacterial collagenase injection. Fingolimod (0.5 mg/kg) or saline was administered intraperitoneally after 0.5, 24 and 72 h, in a randomized and blinded manner. Functional improvement with cylinder, wire hanging, and foot fault tests was evaluated one and two weeks later. Lesion volume and hemispheric atrophy were quantified at the 14-day endpoint. There was a higher mortality in saline-treated females compared to fingolimod-treated females and saline-treated males. There was no treatment- or gender-related difference in the behavioural tests. Histological outcome measures did not differ between any of the groups. These results, contrasting with those of previous studies of fingolimod in experimental ICH, emphasize the importance of rigorous testing of this agent in models more representative of the clinical situation.
脑出血（ICH）尚无特异性治疗方法，但占所有中风病例的比例高达15%，且死亡率最高。芬戈莫德（FTY720）是一种已被批准用于治疗多发性硬化症的免疫调节剂，在实验性缺血性中风中有大量疗效证据，而在实验性脑出血中的证据较为有限。本研究的目的是通过严格且具有充分统计学效力的研究来证实芬戈莫德在实验性脑出血中的疗效。通过纹状体内注射细菌胶原酶在C57BL/6JOlaHsd雄性和雌性小鼠中诱导脑出血。在0.5、24和72小时后，以随机和盲法腹腔注射芬戈莫德（0.5毫克/千克）或生理盐水。在1周和2周后通过圆筒试验、悬线试验和足误试验评估功能改善情况。在第14天的终点对损伤体积和半球萎缩进行定量分析。与芬戈莫德治疗的雌性小鼠和生理盐水治疗的雄性小鼠相比，生理盐水治疗的雌性小鼠死亡率更高。行为测试中未发现与治疗或性别相关的差异。各实验组之间的组织学结果指标没有差异。这些结果与之前关于芬戈莫德在实验性脑出血中的研究结果形成对比，强调了在更具临床代表性的模型中对该药物进行严格测试的重要性。
