Kalayci Rivaze, Kaya Mehmet, Ahishali Bulent, Arican Nadir, Elmas Imdat, Kucuk Mutlu
Research Institute for Experimental Medicine, Istanbul University, Capa 34390, Istanbul, Turkey.
Life Sci. 2006 May 30;79(1):16-20. doi: 10.1016/j.lfs.2005.12.034. Epub 2006 Jan 24.
We investigated whether the severity of blood-brain barrier disruption caused by pentylenetetrazole-induced seizures is modified by long-term nitric oxide synthase inhibition in rats. Rats were given N-omega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in drinking water for 4 weeks, and then treated with pentylenetetrazole to induce seizures. Damage to the blood-brain barrier was investigated using Evans blue dye extravasation. Serum nitric oxide concentration was decreased in L-NAME-treated rats (P<0.01). L-NAME and/or pentylenetetrazole treatments elevated systolic blood pressure of animals (P<0.01). L-NAME caused an increase in the mortality rate after pentylenetetrazole injection leading to the death of animals at about 15 min after the onset of the seizure. Pentylenetetrazole-induced seizures in rats treated with L-NAME caused a significant increase in Evans blue dye extravasation into cerebral cortex, diencephalon and cerebellum, as compared with seizures evoked by pentylenetetrazole injection to L-NAME-untreated rats (P<0.01). Data presented here suggest that the degree of blood-brain barrier disruption induced by seizures is more pronounced in long-term nitric oxide deficiency.
我们研究了长期抑制大鼠一氧化氮合酶是否会改变戊四氮诱导的癫痫发作所引起的血脑屏障破坏的严重程度。给大鼠饮用含一氧化氮合酶抑制剂N-ω-硝基-L-精氨酸甲酯（L-NAME）的水4周，然后用戊四氮诱导癫痫发作。使用伊文思蓝染料外渗法研究血脑屏障的损伤情况。L-NAME处理的大鼠血清一氧化氮浓度降低（P<0.01）。L-NAME和/或戊四氮处理使动物的收缩压升高（P<0.01）。L-NAME导致戊四氮注射后死亡率增加，致使动物在癫痫发作开始后约15分钟死亡。与未用L-NAME处理的大鼠注射戊四氮诱发的癫痫发作相比，用L-NAME处理的大鼠中戊四氮诱发的癫痫发作导致伊文思蓝染料向大脑皮层、间脑和小脑的外渗显著增加（P<0.01）。此处呈现的数据表明，在长期一氧化氮缺乏的情况下，癫痫发作诱导的血脑屏障破坏程度更为明显。
