Ostrovskaya R U, Romanova G A, Barskov I V, Shanina E V, Gudasheva T A, Victorov I V, Voronina T A, Seredenin S B
Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow, Russia.
Behav Pharmacol. 1999 Sep;10(5):549-53. doi: 10.1097/00008877-199909000-00013.
Local thrombosis of the frontal cortex (Fr1 and Fr3 fields), caused by combination of the intravenous photosensitive dye Rose Bengal administration with focused high-intensity illumination of the frontal bone, was shown to provoke a pronounced deficit in step-through passive avoidance performance in rats without concomitant motor disturbances. N-Phenylacetyl-L-prolylglycine ethyl ester (GVS-111) administered intravenously at a dose of 0.5 mg/kg/day, for the first time 1 h after ischaemic lesion and then for 9 post-operative days, with the last administration 15 min before testing, attenuated the deficit. This treatment significantly diminished the volume of the infarcted area. Thus, post-ischaemic injection of GVS-111 demonstrated both cognition-restoring and neuroprotective properties. The cognition-restoring effect is probably based on an increase in neocortical and hippocampal neuronal plasticity. Neuroprotective effects of GVS-111 combine antioxidant activity with the ability to attenuate glutamate-provoked neurotoxicity and block voltage-gated ionic channels, i.e. the compound mitigates the main metabolic shifts involved in pathogenesis of brain ischaemia.
静脉注射光敏染料孟加拉玫瑰红并对额骨进行聚焦高强度照射相结合，导致额叶皮质（Fr1和Fr3区域）局部血栓形成，结果显示这会引发大鼠穿梭箱被动回避行为的显著缺陷，且无伴随的运动障碍。以0.5毫克/千克/天的剂量静脉注射N-苯乙酰-L-脯氨酰甘氨酸乙酯（GVS-111），在缺血性损伤后1小时首次给药，然后在术后9天给药，最后一次给药在测试前15分钟，可减轻这种缺陷。这种治疗显著减少了梗死面积。因此，缺血后注射GVS-111显示出认知恢复和神经保护特性。认知恢复作用可能基于新皮质和海马神经元可塑性的增加。GVS-111的神经保护作用将抗氧化活性与减轻谷氨酸诱发的神经毒性以及阻断电压门控离子通道的能力相结合，即该化合物减轻了脑缺血发病机制中涉及的主要代谢变化。
