Michelson H B, Lothman E W
Department of Neurology, University of Virginia Health Sciences Center, Charlottesville 22908.
Brain Res Dev Brain Res. 1992 Apr 24;66(2):237-43. doi: 10.1016/0165-3806(92)90085-b.
In vivo experiments were carried out to examine whether the period during which gamma-aminobutyric acid (GABA)ergic inhibition in the hippocampus matures is associated with a decrease in epileptogenesis. Seizures were elicited with bipolar electrodes stereotactically positioned in the hippocampus of urethane-anesthetized rat pups from postnatal (PN) 7 through 28 days of age. No clinical seizure activity was detected but electrographic seizures (afterdischarges) were induced at all ages. Afterdischarge thresholds (ADT) varied inversely with age. However, the durations of initial afterdischarges and the degree of lengthening of afterdischarges with the rapidly recurring hippocampal seizure (RRHS) protocol were not different for the various age animals studied. Paired pulse inhibition was assessed with a twin pulse paradigm that has been shown to monitor GABAergic inhibition. Measurements were made before and 60 min after a single seizure and again 60 min after the RRHS protocol. At no age was there a significant change in paired pulse inhibition after a single seizure. After RRHS there was a significant reduction of paired pulse inhibition only in the groups that had manifested adult levels of paired pulse inhibition in pre-seizure measurements (greater than or equal to PN 21). These studies indicate that heightened epileptogenesis in the young hippocampus cannot simply be explained on the basis of an immaturity of GABA-mediated inhibition.
进行了体内实验，以检查海马体中γ-氨基丁酸（GABA）能抑制成熟的时期是否与癫痫发生的减少有关。使用双极电极在立体定位下诱发癫痫发作，该电极位于出生后（PN）7至28天的经乌拉坦麻醉的幼鼠海马体中。未检测到临床癫痫活动，但在所有年龄段均诱发了脑电图癫痫发作（放电后）。放电后阈值（ADT）与年龄呈反比。然而，对于所研究的不同年龄动物，初始放电后的持续时间以及快速复发性海马癫痫发作（RRHS）方案下放电后的延长程度并无差异。使用已被证明可监测GABA能抑制的双脉冲范式评估配对脉冲抑制。在单次癫痫发作前和发作后60分钟以及RRHS方案后60分钟再次进行测量。在任何年龄，单次癫痫发作后配对脉冲抑制均无显著变化。RRHS后，仅在癫痫发作前测量中表现出成人水平配对脉冲抑制（大于或等于PN 21）的组中，配对脉冲抑制有显著降低。这些研究表明，幼龄海马体中癫痫发生的增加不能简单地基于GABA介导的抑制不成熟来解释。
