Wang Jinqiao, Ma Chunyan, Zhu Jing, Rao Gaofeng, Li Hongjuan
Department of Rehabilitation Medicine, The First People's Hospital of Wenling, Wenzhou Medical University, Wenling, Zhejiang, China.
College of Pharmacy, the Ohio State University, Columbus, OH, USA.
Dose Response. 2020 Jan 22;18(1):1559325819901242. doi: 10.1177/1559325819901242. eCollection 2020 Jan-Mar.
The disruption of blood-brain barrier (BBB) is a critical event in the formation of brain edema during early phases of ischemic brain injury. Poly(ADP-ribose) polymerase (PARP) activation, which contributes to BBB damage, has been reported in ischemia-reperfusion and traumatic brain injury. Here, we investigated the effect of 3-aminobenzamide (3-AB), a PARP-1 inhibitor, on the ultrastructure of BBB. Male Sprague Dawley rats were suffered from 90 minutes of middle cerebral artery occlusion, followed by 4.5 hours or 22.5 hours of reperfusion (R). The vehicle or 3-AB (10 mg/kg) was administered intraperitoneally (ip) 60 minutes after lacking of blood. Tissue Evans Blue (EB) levels, ultrastructures of astrocytes and microvessels, and areas of perivascular edema were examined in penumbra and core, at I 1.5 hours /R 4.5 hours and I 1.5 hours /R 22.5 hours, respectively. The severity of ultrastructural changes was graded with a scoring system in each group. We showed that 3-AB treatment significantly decreased tissue EB levels and ultrastructural scores, attenuated damages in astrocytes and microvessels, and reduced areas of perivascular edema. In conclusion, PARP inhibition may provide a novel therapeutic approach to ischemic brain injury.
血脑屏障（BBB）的破坏是缺血性脑损伤早期脑水肿形成过程中的关键事件。聚（ADP-核糖）聚合酶（PARP）激活会导致血脑屏障损伤，这在缺血再灌注和创伤性脑损伤中已有报道。在此，我们研究了PARP-1抑制剂3-氨基苯甲酰胺（3-AB）对血脑屏障超微结构的影响。雄性Sprague Dawley大鼠经历90分钟大脑中动脉闭塞，随后进行4.5小时或22.5小时的再灌注（R）。缺血60分钟后腹腔注射（ip）溶剂或3-AB（10mg/kg）。分别在缺血1.5小时/再灌注4.5小时和缺血1.5小时/再灌注22.5小时时，检测半暗带和梗死核心区的伊文思蓝（EB）组织水平、星形胶质细胞和微血管的超微结构以及血管周围水肿面积。每组采用评分系统对超微结构变化的严重程度进行分级。我们发现，3-AB治疗可显著降低组织EB水平和超微结构评分，减轻星形胶质细胞和微血管损伤，并减少血管周围水肿面积。总之，抑制PARP可能为缺血性脑损伤提供一种新的治疗方法。
