Ferraro T N, Golden G T, Smith G G, Berrettini W H
Department of Psychiatry and Pharmacology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.
Epilepsia. 1995 Mar;36(3):301-7. doi: 10.1111/j.1528-1157.1995.tb00999.x.
Mature DBA/2J (D2) and C57BL/6J (B6) mice aged 9-10 weeks were studied to determine susceptibility to behavioral seizures induced by kainic acid (KA) and the possible influence exerted by differences in metabolism and blood-brain barrier (BBB) transport. Mice were observed for 4 h after subcutaneous (s.c.) KA injection. Behavioral seizure parameters included latency to first seizure (clonus), latency to tonic/clonic seizure, and latency to status epilepticus (SE). At a KA dose of 25 mg/kg, 80% of D2 mice exhibited tonic/clonic seizures, whereas all B6 mice remained seizure-free. At 30 mg/kg, tonic/clonic seizures were observed in 100% of D2 mice and 25% of B6 mice. Of D2 mice exhibiting at least one clonic seizure in response to KA at a dose of 25 mg/kg, 50% entered SE and eventually died. Administration of [3H]KA (6.6 x 10(6) dpm) at doses of 25 mg/kg (convulsive) or 11.1 micrograms (nonconvulsive) to mice of both strains resulted in similar levels of radioactivity in cortex, hippocampus, and cerebellum 30 and 60 min after injection. Bioconversion of [3H]KA to a radiolabeled brain metabolite in vivo could not be documented in mice from either strain. Results confirm previously reported differences between D2 and B6 mice in their relative susceptibility to seizures induced by systemic KA administration and suggest that these differences are not related to strain-specific variation in metabolism or BBB transport of KA. Further studies of these two strains of mice may be useful for investigating genetic influences upon seizure susceptibility.
对9 - 10周龄的成熟DBA/2J（D2）和C57BL/6J（B6）小鼠进行研究，以确定对海藻酸（KA）诱导的行为性癫痫发作的易感性，以及代谢差异和血脑屏障（BBB）转运可能产生的影响。皮下注射KA后观察小鼠4小时。行为性癫痫发作参数包括首次发作（阵挛）的潜伏期、强直/阵挛发作的潜伏期和癫痫持续状态（SE）的潜伏期。KA剂量为25 mg/kg时，80%的D2小鼠出现强直/阵挛发作，而所有B6小鼠均未发作。剂量为30 mg/kg时，100%的D2小鼠和25%的B6小鼠出现强直/阵挛发作。在剂量为25 mg/kg时对KA有至少一次阵挛发作的D2小鼠中，50%进入癫痫持续状态并最终死亡。以25 mg/kg（惊厥性）或11.1微克（非惊厥性）的剂量给两种品系的小鼠注射[3H]KA（6.6×10(6) dpm），注射后30分钟和60分钟时，皮质、海马和小脑中的放射性水平相似。在任何一个品系的小鼠体内均未发现[3H]KA在体内生物转化为放射性标记的脑代谢物。结果证实了先前报道的D2和B6小鼠在全身注射KA诱导的癫痫发作相对易感性方面的差异，并表明这些差异与KA的代谢或血脑屏障转运的品系特异性变异无关。对这两种品系小鼠的进一步研究可能有助于调查遗传对癫痫易感性的影响。
