Williamson John, Mtchedlishvili Zakaria, Kapur Jaideep
Department of Neurology, University of Virginia, Health Sciences Center, Box 800394, Charlottesville, VA 22908-0394, USA.
Neuropharmacology. 2004 May;46(6):856-64. doi: 10.1016/j.neuropharm.2003.11.029.
Pregnenolone sulfate (PS) is an endogenous neurosteroid synthesized by glial cells, which acts as a potent convulsant when injected intracerebroventricularly and intraperitoneally. PS is found in relatively high concentrations in the hippocampus. But its convulsant action in the hippocampus has not been characterized. A range of PS doses were infused directly into the right hippocampus of 42 rats, which were subsequently monitored for behavioral and electrographic seizures. At the highest dose (4 micromol), PS produced status epilepticus (SE) and severe behavioral convulsions. As the dose of PS was reduced, the fraction of rats having SE diminished (ED50 for SE = 2.7 micromol). At doses lower than 300 nmol, PS infusion produced discrete electrographic seizures (ED50 = 68 nmol) associated with mild behavioral seizures. Both the behavioral seizure score (BSS) and the total number of seizures during the observation period changed in a dose-dependent manner. In separate experiments in cultured hippocampal neurons, PS enhanced NMDA-evoked whole-cell currents (EC50 = 16 microM). The results demonstrate that the hippocampus is highly sensitive to the convulsant effects of PS and that the enhancement of NMDA currents could contribute to the convulsant action of PS.
硫酸孕烯醇酮（PS）是一种由神经胶质细胞合成的内源性神经甾体，当经脑室和腹腔注射时，它作为一种强效惊厥剂起作用。在海马体中发现PS的浓度相对较高。但其在海马体中的惊厥作用尚未得到明确描述。将一系列剂量的PS直接注入42只大鼠的右侧海马体，随后监测其行为和脑电图癫痫发作情况。在最高剂量（4微摩尔）时，PS引发癫痫持续状态（SE）和严重的行为惊厥。随着PS剂量的降低，发生SE的大鼠比例减少（SE的半数有效剂量[ED50]=2.7微摩尔）。在低于300纳摩尔的剂量下，注入PS会产生与轻度行为性癫痫发作相关的离散脑电图癫痫发作（ED50=68纳摩尔）。行为癫痫发作评分（BSS）和观察期内癫痫发作的总数均呈剂量依赖性变化。在培养的海马神经元的单独实验中，PS增强了NMDA诱发的全细胞电流（半数有效浓度[EC50]=16微摩尔）。结果表明，海马体对PS的惊厥作用高度敏感，NMDA电流的增强可能促成了PS的惊厥作用。
