雌激素治疗可保护海人酸诱导的癫痫持续状态后雌性大鼠齿状回中的GABA(B)抑制作用。

Estrogen treatment protects GABA(B) inhibition in the dentate gyrus of female rats after kainic acid-induced status epilepticus.

作者信息

Velísek Libor, Velísková Jana

机构信息

Department of Neurology K312, Albert Einstein College of Medicine, 1410 Pelham Parkway South, Bronx, NY 10461, U.S.A.

出版信息

Epilepsia. 2002;43 Suppl 5:146-51. doi: 10.1046/j.1528-1157.43.s.5.3.x.

DOI:10.1046/j.1528-1157.43.s.5.3.x

PMID:12121310

Abstract

PURPOSE

We used the paired-pulse inhibition paradigm to determine whether the cell loss in the hilus of the dentate gyrus of female rats after kainic acid (KA)-induced status epilepticus (SE) is associated with functional changes in the dentate gyrus. Additionally, we determined whether the lost function could be preserved by using estrogen neuroprotection.

METHODS

Female rats were ovariectomized and treated either with estrogen replacement (four doses of 2 microg of estradiol every 24 h: two doses before SE, two doses after) or oil. SE was induced by I.P. administration of KA (16 mg/kg) and terminated after 5 h with pentobarbital. After 2 days, hippocampal/dentate gyrus slices were prepared. Population spikes were recorded in the granule cell layer as a response to mixed perforant-path stimulation (10- to 1,000-ms interstimulus intervals). Ratios of the test response to conditioning response were evaluated. Gamma-aminobutyric acid type B (GABAB) receptors were blocked with 400 microM CGP 35348.

RESULTS

In slices from oil-treated rats, SE induced a loss of paired-pulse inhibition in the dentate gyrus at the interstimulus intervals marking intermediate facilitation and late depression. There was no such loss of paired-pulse inhibition in estrogen-treated rats. CGP 35348 was unable to alter paired-pulse inhibition in slices form oil-treated rats. In slices from estrogen-treated rats, CGP decreased paired-pulse inhibition at 50-150-ms interstimulus intervals. Comparison of paired-pulse inhibition in slices from oil-treated rats with slices from estrogen-treated rats with CGP 35348 revealed a GABAB-independent difference at interstimulus intervals >300 ms.

CONCLUSIONS

Our study demonstrated that there is a complete loss of GABAB receptor-mediated inhibition after KA-induced SE in the dentate gyrus. Pretreatment with estrogen can save GABAB-receptor function, probably by neuroprotection of neurons containing the postsynaptic GABAB receptors.

摘要

目的

我们采用配对脉冲抑制范式来确定海藻酸（KA）诱导的癫痫持续状态（SE）后雌性大鼠齿状回门区的细胞丢失是否与齿状回的功能变化有关。此外，我们还确定了使用雌激素神经保护能否保留丧失的功能。

方法

对雌性大鼠进行卵巢切除，并给予雌激素替代治疗（每24小时注射4剂2微克雌二醇：SE发作前2剂，发作后2剂）或给予油剂。通过腹腔注射KA（16毫克/千克）诱导SE，并在5小时后用戊巴比妥终止。2天后，制备海马/齿状回切片。在颗粒细胞层记录群体峰电位，作为对混合穿通通路刺激（刺激间隔为10至1000毫秒）的反应。评估测试反应与条件反应的比率。用400微摩尔/升CGP 35348阻断γ-氨基丁酸B型（GABAB）受体。

结果

在油剂处理大鼠的切片中，SE在标记中间易化和晚期抑制的刺激间隔下诱导齿状回配对脉冲抑制丧失。在雌激素处理的大鼠中没有这种配对脉冲抑制丧失。CGP 35348不能改变油剂处理大鼠切片中的配对脉冲抑制。在雌激素处理大鼠的切片中，CGP在50至150毫秒的刺激间隔下降低了配对脉冲抑制。比较油剂处理大鼠切片与用CGP 35348处理的雌激素处理大鼠切片中的配对脉冲抑制，发现在刺激间隔>300毫秒时存在不依赖GABAB的差异。