Gupta Ramesh C, Milatovic Dejan, Zivin Marko, Dettbarn Wolf-D
Murray State University, Hopkinsville, KY 42241, USA, USA.
Departments of Pharmacology and Neurology, Vanderbilt University, School of Medicine, Nashville, TN 37212, USA, USA.
Pflugers Arch. 2000 Jan;440(Suppl 1):R160-R162. doi: 10.1007/s004240000047.
Impaired energy metabolism may play a critical role in the neuronal injury caused by kainic acid (KA) induced status epilepticus (SE). Following an acute dose of KA (15 mg/kg, sc) rats developed SE within 1 h. Rats were sacrificed 1 or 72 h after the onset of SE using a head focused microwave technique and the brain regions (pyriform cortex, amygdala, and hippocampus) were assayed for energy metabolites: ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) using reversed-phase HPLC (RP-HPLC). Control values were significantly higher in cortex (23-32%) than in other brain regions. Within 1 h, SE caused a marked decline in ATP (44-56%), PCr (49-64%), total adenine nucleotides (TAN, 45-50%) and total creatine compounds (TCC, 32-51%). Within three days, the hippocampus showed the greatest recovery, as the reduced values returned to normal. Pretreatment of rats with an antioxidant (PBN, 200 mg/kg, ip, 30 min prior to KA; or vitamin E (Vit-E), 100 mg/kg, ip/day for 3 days), which did not prevent seizure activity, attenuated depletion of high-energy phosphates caused by KA. These findings suggest that the depletion of energy metabolites caused by KA-induced seizures may be linked to oxidative stress mediated toxicity.
能量代谢受损可能在 kainic 酸（KA）诱导的癫痫持续状态（SE）所引起的神经元损伤中起关键作用。给予大鼠急性剂量的 KA（15 mg/kg，皮下注射）后，1 小时内出现 SE。使用头部聚焦微波技术在 SE 发作后 1 小时或 72 小时处死大鼠，用反相高效液相色谱（RP-HPLC）测定脑区（梨状皮质、杏仁核和海马体）中的能量代谢物：ATP、ADP、AMP、磷酸肌酸（PCr）和肌酸（Cr）。皮质中的对照值显著高于其他脑区（23 - 32%）。1 小时内，SE 导致 ATP（44 - 56%）、PCr（49 - 64%）、总腺嘌呤核苷酸（TAN，45 - 50%）和总肌酸化合物（TCC，32 - 51%）显著下降。三天内，海马体恢复程度最大，降低的值恢复至正常。用抗氧化剂预处理大鼠（PBN，200 mg/kg，腹腔注射，在 KA 前 30 分钟；或维生素 E（Vit-E），100 mg/kg，腹腔注射，每天 1 次，共 3 天），虽不能预防癫痫发作活动，但可减轻 KA 引起的高能磷酸盐消耗。这些发现表明，KA 诱导的癫痫发作所导致的能量代谢物耗竭可能与氧化应激介导的毒性有关。
