Department of Neurological Surgery, University of Wisconsin, Madison, WI, USA.
Cellular and Molecular Pathology Graduate Program, University of Wisconsin, Madison, WI, USA.
J Cereb Blood Flow Metab. 2022 Feb;42(2):253-263. doi: 10.1177/0271678X211056392. Epub 2021 Oct 25.
The role of tenascin-C (TNC) in ischemic stroke pathology is not known despite its prognostic association with cerebrovascular diseases. Here, we investigated the effect of TNC knockdown on post-stroke brain damage and its putative mechanism of action in adult mice of both sexes. Male and female C57BL/6 mice were subjected to transient middle cerebral artery occlusion and injected (i.v.) with either TNC siRNA or a negative (non-targeting) siRNA at 5 min after reperfusion. Motor function (beam walk and rotarod tests) was assessed between days 1 and 14 of reperfusion. Infarct volume (T2-MRI), BBB damage (T1-MRI with contrast), and inflammatory markers were measured at 3 days of reperfusion. The TNC siRNA treated cohort showed significantly curtailed post-stroke TNC protein expression, motor dysfunction, infarction, BBB damage, and inflammation compared to the sex-matched negative siRNA treated cohort. These results demonstrate that the induction of TNC during the acute period after stroke might be a mediator of post-ischemic inflammation and secondary brain damage independent of sex.
尽管 tenascin-C（TNC）与脑血管疾病的预后相关，但它在缺血性中风发病机制中的作用尚不清楚。在这里，我们研究了 TNC 敲低对成年雄性和雌性小鼠卒中后脑损伤的影响及其可能的作用机制。雄性和雌性 C57BL/6 小鼠在再灌注后 5 分钟通过静脉注射 TNC siRNA 或阴性（非靶向）siRNA 进行短暂性大脑中动脉闭塞。在再灌注的第 1 天至第 14 天之间评估运动功能（横梁行走和转棒测试）。在再灌注 3 天时测量梗死体积（T2-MRI）、BBB 损伤（T1-MRI 与对比）和炎症标志物。与性别匹配的阴性 siRNA 处理组相比，TNC siRNA 处理组的 TNC 蛋白表达、运动功能障碍、梗死、BBB 损伤和炎症明显减少。这些结果表明，卒中后急性期 TNC 的诱导可能是缺血后炎症和继发性脑损伤的介质，与性别无关。
