Baran H, Vass K, Lassmann H, Hornykiewicz O
Institute of Biochemical Pharmacology, University of Vienna, Austria.
Brain Res. 1994 May 23;646(2):201-6. doi: 10.1016/0006-8993(94)90078-7.
In this study the effect of the anti-inflammatory drugs indomethacin, ibuprofen, ebselen (PZ 51, 2-phenyl-1,2-benzoisoselenazol-3(2H)-one), and BW755C (3-amino-1-(m-(trifluoromethyl-phenyl)-2-pyrazoline) on kainic acid (KA)-induced behavioral and neurochemical changes in rats was investigated. Rats injected with KA (10 mg/kg s.c.) developed seizure activity with a 20% mortality within the first 4 h and neuronal degeneration in the limbic system after 3 days. Pretreatment with the cyclooxygenase inhibitor indomethacin (10 mg/kg i.p.) augmented KA-induced epileptic activity and increased the mortality in status epilepticus to 80%. Another cyclooxygenase inhibitor, ibuprofen (20 mg/kg i.p.), and the lipoxygenase inhibitor ebselen (20 mg/kg i.p.) showed no effect on KA-induced symptoms and neurochemical changes. Application of the cyclooxygenase/lipoxygenase inhibitor BW755C (40 mg/kg i.p.) reduced the severity of seizures and protected significantly from irreversible brain lesions induced by KA. The marked reduction of glutamate decarboxylase (GAD; 53.3 +/- 12.2% of control) and choline acetyltransferase (ChAT; 60.9 +/- 9.1% of control) activities in amygdala/pyriform cortex and GAD activity in hippocampus (69.4 +/- 5.6% of control) observed 3 days after KA injection was abolished by BW755C treatment. Histopathological analyses of brain tissue showed that treatment with BW755C prevented the KA-induced nerve cell degeneration, edema, hemorrhages, and tissue necrosis in amygdala/pyriform cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
在本研究中，调查了消炎药物吲哚美辛、布洛芬、依布硒啉（PZ 51，2-苯基-1,2-苯并异硒唑-3(2H)-酮）和BW755C（3-氨基-1-(间-(三氟甲基)苯基)-2-吡唑啉）对红藻氨酸（KA）诱导的大鼠行为和神经化学变化的影响。注射KA（10 mg/kg皮下注射）的大鼠在最初4小时内出现癫痫活动，死亡率为20%，3天后边缘系统出现神经元变性。用环氧化酶抑制剂吲哚美辛（10 mg/kg腹腔注射）预处理可增强KA诱导的癫痫活动，并使癫痫持续状态的死亡率增加至80%。另一种环氧化酶抑制剂布洛芬（20 mg/kg腹腔注射）和脂氧化酶抑制剂依布硒啉（20 mg/kg腹腔注射）对KA诱导的症状和神经化学变化无影响。应用环氧化酶/脂氧化酶抑制剂BW755C（40 mg/kg腹腔注射）可降低癫痫发作的严重程度，并显著保护大鼠免受KA诱导的不可逆脑损伤。KA注射3天后在杏仁核/梨状皮层观察到的谷氨酸脱羧酶（GAD；为对照的53.3 +/- 12.2%）和胆碱乙酰转移酶（ChAT；为对照的60.9 +/- 9.1%）活性的显著降低以及海马中GAD活性（为对照的69.4 +/- 5.6%）的降低被BW755C治疗所消除。脑组织的组织病理学分析表明，BW755C治疗可预防KA诱导的杏仁核/梨状皮层神经细胞变性、水肿、出血和组织坏死。（摘要截断于250字）
