Perron Institute for Neurological and Translational Science, Nedlands, Australia; Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, Western Australia, Australia; School of Heath Sciences, The University Notre Dame Australia, Fremantle, Western Australia, Australia.
Perron Institute for Neurological and Translational Science, Nedlands, Australia; Department of Neurosurgery, Sir Charles Gairdner Hospital, QEII Medical Centre, Nedlands, Western Australia, Australia; Centre for Neuromuscular and Neurological Disorders, The University of Western Australia, Nedlands, Australia.
Brain Res Bull. 2017 Oct;135:62-68. doi: 10.1016/j.brainresbull.2017.09.012. Epub 2017 Sep 28.
Following positive results with the poly-arginine peptide R18 when administered intravenously 30 or 60min after permanent and/or transient middle cerebral artery occlusion (MCAO; 90min) in the rat, we examined the effectiveness of the peptide when administered 2h after MCAO. R18 was administered intravenously (1000nmol/kg via jugular vein) after permanent MCAO or a transient 3-h MCAO or when administered intra-arterially (100nmol/kg via internal carotid artery) immediately after reperfusion following a transient 2-h MCAO. In the transient MCAO studies, the neuroprotective NA-1 peptide was used as a positive control. Infarct volume, cerebral edema and functional outcomes were measured 24h after MCAO. Following permanent or transient MCAO, neither R18 nor NA-1 significantly reduced infarct volume. However, following permanent MCAO, R18 appeared to reduce cerebral edema (p=0.006), whereas following a transient 3-h MCAO, R18 improved the time to remove adhesive tape (p=0.04) without significantly affecting cerebral edema. There was also a trend (p=0.07) towards improved rota-rod performance with R18 in both permanent and transient 3-h MCAO. Following a transient 2-h MCAO, R18 had no significant effects on cerebral edema or neurological score but did lessen the extent of weight loss. Overall, while R18 had no effect on infarct volume, the peptide reduced cerebral edema after permanent MCAO, and improved some functional outcomes after transient MCAO.
在大鼠永久性和/或短暂性大脑中动脉闭塞（MCAO；90 分钟）后 30 或 60 分钟静脉内给予多精氨酸肽 R18 产生积极结果后，我们研究了肽在 MCAO 后 2 小时给药时的有效性。R18 在永久性 MCAO 或短暂 3 小时 MCAO 后通过颈静脉（1000nmol/kg）静脉内给药，或在短暂 2 小时 MCAO 后再灌注时通过颈内动脉（100nmol/kg）动脉内给药。在短暂性 MCAO 研究中，NA-1 肽被用作阳性对照。MCAO 后 24 小时测量梗塞体积、脑水肿和功能结果。在永久性或短暂性 MCAO 后，R18 和 NA-1 均未显著减少梗塞体积。然而，在永久性 MCAO 后，R18 似乎减少脑水肿（p=0.006），而在短暂 3 小时 MCAO 后，R18 改善了去除胶带的时间（p=0.04），而没有显著影响脑水肿。永久性和短暂性 3 小时 MCAO 中，R18 也有改善旋转棒性能的趋势（p=0.07）。在短暂性 2 小时 MCAO 后，R18 对脑水肿或神经评分没有显著影响，但减轻了体重减轻的程度。总的来说，虽然 R18 对梗塞体积没有影响，但该肽可减轻永久性 MCAO 后的脑水肿，并改善短暂性 MCAO 后的一些功能结果。
