Bagetta G, Iannone M, Vecchio I, Rispoli V, Rotiroti D, Nisticó G
Faculty of Pharmacy, Calabria University, Cosenza, Italy.
Free Radic Res. 1994 Aug;21(2):85-93. doi: 10.3109/10715769409056560.
The behavioural, electrocortical (ECoG) and neurodegenerative effects of intrahippocampal injection of paraquat, a well-known free radical producing agent, were studied in rats. Injection of paraquat (100 nmol) into one dorsal hippocampus produced limbic motor and ECoG seizures. These effects were accompanied at 24 h by severe damage to CA1, CA3 and CA4 hippocampal pyramidal neurones and dentate gyrus granule cells. In comparison to the cell number counted in control, untreated, side of the hippocampus, significant (P < 0.05) neuronal loss was observed in the CA1 and CA3 pyramidal cell layers of the treated hippocampus. A lower dose of the herbicide (10 nmol) did not produce consistent motor and ECoG effects and in no instance was significant neuronal loss observed. A pretreatment with U74389F [21-4-(2,6-di-l-pyrrodinyl-4-pyridinyl)-1-piperazinyl-pregna-1,4,9 (11)triene-3,20-dione monomethansulfonate] (30 mg/kg i.p., 15 min before paraquat) completely protected rats from motor and ECoG epileptogenic effects induced by intrahippocampal paraquat (100 nmol). This dose of U74389F also reduced the hippocampal damage typically produced by paraquat and no significant neuronal loss was reported in the CA1 and CA3 pyramidal cell layers. A lower dose of U74389F (10 mg/kg i.p.) did not afford any protection against the epileptogenic effects produced by paraquat (100 nmol); in these animals hippocampal damage was still evident though neuronal loss did not reach statistical significance. In conclusion, the present data show that systemic administration of U74389F possesses neuroprotective effects against seizures and neurodegeneration typically elicited by intrahippocampal injection of paraquat.
在大鼠中研究了向海马体内注射百草枯（一种著名的自由基生成剂）的行为、皮层脑电图（ECoG）和神经退行性影响。向一侧背侧海马注射百草枯（100纳摩尔）会引发边缘运动和ECoG癫痫发作。这些影响在24小时时伴有海马CA1、CA3和CA4区锥体细胞以及齿状回颗粒细胞的严重损伤。与未处理的对照侧海马中计数的细胞数量相比，在处理侧海马的CA1和CA3锥体细胞层中观察到显著（P<0.05）的神经元损失。较低剂量的除草剂（10纳摩尔）未产生一致的运动和ECoG影响，且在任何情况下均未观察到显著的神经元损失。用U74389F[21-4-(2,6-二-1-吡咯烷基-4-吡啶基)-1-哌嗪基-孕甾-1,4,9(11)三烯-3,20-二酮单甲磺酸盐]（30毫克/千克腹腔注射，在注射百草枯前15分钟）进行预处理可使大鼠完全免受海马内注射百草枯（100纳摩尔）诱导的运动和ECoG致痫作用。该剂量的U74389F还减少了通常由百草枯产生的海马损伤，并且在CA1和CA3锥体细胞层中未报告有显著的神经元损失。较低剂量的U74389F（10毫克/千克腹腔注射）不能为百草枯（100纳摩尔）产生的致痫作用提供任何保护；在这些动物中，尽管神经元损失未达到统计学意义，但海马损伤仍然明显。总之，目前的数据表明，全身性给予U74389F对海马内注射百草枯通常引发的癫痫发作和神经退行性变具有神经保护作用。
