Li Jun, Henman Martin C, Tatlisumak Turgut, Shaw Graham G, Doyle Karen M
Department of Pharmacology, School of Pharmacy, Trinity College Dublin, Ireland.
Brain Res. 2005 Sep 7;1055(1-2):180-5. doi: 10.1016/j.brainres.2005.07.023.
The pre-ischaemic neuroprotective potential of a novel polyamine/NMDA antagonist N1-dansyl-spermine (1-5 mg kg(-1)) was studied in a transient focal cerebral ischaemia model in mice in comparison to a reference compound, MK-801 (1 or 3 mg kg(-1)). The intraluminal suture transient middle cerebral artery occlusion (MCAO) model was used. N1-dansyl-spermine and MK-801 were administered (i.p.) 30 min prior to ischaemia. A range of histological and behavioural assessments was employed. N1-dansyl-spermine had a comparable effect to MK-801 at reducing the percentage hemisphere lesion volume (%HLV) at the doses tested. Furthermore, N1-dansyl-spermine reduced the ischaemic brain oedema, which MK-801 did not. N1-dansyl-spermine significantly reversed the decrease of locomotor activity (LMA) caused by the MCAO and showed a significant effect at improving the rotarod performance impaired by MCAO. In contrast, MK-801 had no beneficial effect on sensorimotor function and even worsened the LMA. These results clearly demonstrate the pre-ischaemic neuroprotective effect of N1-dansyl-spermine in a transient focal cerebral ischaemia model.
与参考化合物MK-801（1或3 mg kg⁻¹）相比，在小鼠短暂性局灶性脑缺血模型中研究了新型多胺/NMDA拮抗剂N1-丹磺酰精胺（1 - 5 mg kg⁻¹）缺血前的神经保护潜力。采用腔内缝合短暂性大脑中动脉闭塞（MCAO）模型。在缺血前30分钟腹腔注射N1-丹磺酰精胺和MK-801。采用了一系列组织学和行为学评估方法。在所测试的剂量下，N1-丹磺酰精胺在降低半球病变体积百分比（%HLV）方面与MK-801具有相当的效果。此外，N1-丹磺酰精胺减轻了缺血性脑水肿，而MK-801则没有。N1-丹磺酰精胺显著逆转了MCAO引起的运动活性（LMA）下降，并在改善MCAO受损的转棒试验表现方面显示出显著效果。相比之下，MK-801对感觉运动功能没有有益作用，甚至使LMA恶化。这些结果清楚地证明了N1-丹磺酰精胺在短暂性局灶性脑缺血模型中的缺血前神经保护作用。
