Department of Neurology, Huanhu Hospital, Tianjin, China.
Department of Neurology, Duke University School of Medicine, Durham, North Carolina, USA.
Stroke Vasc Neurol. 2018 Sep 4;3(4):222-230. doi: 10.1136/svn-2018-000152. eCollection 2018 Dec.
Subarachnoid haemorrhage (SAH) accounts for 3% of all strokes, and is associated with significant morbidity and mortality. There is growing evidence implicating apolipoprotein E (apoE) in mediating adaptive anti-inflammatory and neuroprotective responses following ischaemic and traumatic brain injury. In the current study, we test the efficacy of a small apoE mimetic peptide, CN-105 in a murine model of SAH.
Mice subjected to SAH received repeated intravenous injections of CN-105 every 12 hours for 3 days, with the first dose given 2 hours after injury. Daily functional outcomes were assessed by rotarod and neurological severity score. Haemorrhage grade and cerebral vascular diameters were measured at 5 days post-SAH. Cerebral microgliosis, neuronal degeneration and survival were analysed at 5 and 35 days post-SAH, respectively.
CN-105 reduces histological evidence of inflammation, reduces vasospasm and neuronal injury and is associated with improved long-term behavioural outcomes in a murine model of SAH.
Given its favourable pharmacokinetic profile, central nervous system penetration and demonstration of clinical safety, CN-105 represents an attractive therapeutic candidate for treatment of brain injury associated with SAH.
蛛网膜下腔出血（SAH）占所有中风的 3%，与发病率和死亡率显著相关。越来越多的证据表明载脂蛋白 E（apoE）在介导缺血性和创伤性脑损伤后的适应性抗炎和神经保护反应中起作用。在本研究中，我们在 SAH 的小鼠模型中测试了一种小的 apoE 模拟肽 CN-105 的功效。
接受 SAH 的小鼠每 12 小时接受重复的静脉注射 CN-105，连续 3 天，第一次剂量在损伤后 2 小时给予。通过旋转棒和神经严重程度评分每天评估功能结局。在 SAH 后 5 天测量出血等级和脑血管直径。在 SAH 后 5 天和 35 天分别分析脑小胶质细胞增生、神经元变性和存活情况。
CN-105 可减少炎症的组织学证据，减少血管痉挛和神经元损伤，并与 SAH 小鼠模型中改善的长期行为结果相关。
鉴于其有利的药代动力学特征、中枢神经系统穿透性和临床安全性的证明，CN-105 代表了治疗与 SAH 相关的脑损伤的有吸引力的治疗候选物。
