Yanaka K, Camarata P J, Spellman S R, McCarthy J B, Furcht L T, Low W C
Department of Neurosurgery, University of Minnesota Medical School, Minneapolis, USA.
Neurosurgery. 1997 Mar;40(3):557-63; discussion 563-4. doi: 10.1097/00006123-199703000-00026.
Activated polymorphonuclear leukocytes (PMNs) seem to be directly involved in potentiating ischemic brain injury. Recent work in our laboratory demonstrated that synthetic fibronectin peptides significantly inhibit PMN accumulation in ischemic tissue, reduce the size of infarction, and reduce neurological dysfunction after transient focal cerebral ischemia in rats. The purpose of this study was to examine any dose-related effects (Experiment 1) and the optimal timing of the administration (Experiment 2) of synthetic fibronectin peptide V (FN-C/H-V) to further substantiate the role of the peptide in ameliorating cerebral ischemic damage.
Fifty-six animals were included in the study. We evaluated the efficacy of FN-C/H-V on PMN accumulation in ischemic tissue, infarct size, and neurological outcomes in rats subjected to 1 hour of cerebral ischemia and 48 hours of reperfusion.
In Experiment 1, the animals receiving FN-C/H-V at a dose of 10 to 15 mg/kg of body weight per injection showed significant reduction of PMN accumulation, reduction of infarct size, and improvement of neurological outcomes at 48 hours after reperfusion compared to untreated animals (P < 0.05). In Experiment 2, the animals receiving FN-C/H-V within 3 hours after reperfusion also showed significantly better results than untreated animals (P < 0.05). Despite the treatment delay, the administration of FN-C/H-V inhibited PMN accumulation after reperfusion but did not reduce the size of infarction when administered 6 hours after reperfusion.
These data suggest that relatively late postischemic administration of FN-C/H-V is effective in brain protection after ischemia/reperfusion.
活化的多形核白细胞（PMN）似乎直接参与了缺血性脑损伤的加重过程。我们实验室最近的研究表明，合成纤连蛋白肽能显著抑制缺血组织中PMN的聚集，减小梗死灶大小，并减轻大鼠短暂性局灶性脑缺血后的神经功能障碍。本研究的目的是检验合成纤连蛋白肽V（FN-C/H-V）的剂量相关效应（实验1）和最佳给药时间（实验2），以进一步证实该肽在改善脑缺血损伤中的作用。
本研究纳入了56只动物。我们评估了FN-C/H-V对脑缺血1小时并再灌注48小时的大鼠缺血组织中PMN聚集、梗死灶大小和神经功能结局的影响。
在实验1中，与未治疗的动物相比，每注射一次接受10至15mg/kg体重FN-C/H-V的动物在再灌注48小时时PMN聚集显著减少，梗死灶大小减小，神经功能结局改善（P<0.05）。在实验2中，再灌注后3小时内接受FN-C/H-V的动物也比未治疗的动物表现出显著更好的结果（P<0.05）。尽管治疗延迟，但再灌注6小时后给予FN-C/H-V可抑制再灌注后PMN的聚集，但并未减小梗死灶大小。
这些数据表明，缺血后相对较晚给予FN-C/H-V对缺血/再灌注后的脑保护有效。
