Kaur Mandeep, Gupta Tulika, Gupta Mili, Singla Navneet, Kharbanda Parampreet S, Bansal Yogender Singh, Sahni Daisy, Radotra Bishan Das, Gupta Sunil Kumar
Department of Anatomy, Institute of Medical Education and Research, Chandigarh, India.
Department of Biochemistry, Singh Judge Institute of Dental Sciences and Hospital, Panjab University, Chandigarh, India.
Basic Clin Neurosci. 2023 Sep-Oct;14(5):615-630. doi: 10.32598/bcn.2021.2554.3. Epub 2023 Sep 1.
About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein () and multidrug-resistance associated protein-1 (). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue.
We have studied and drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15).
Statistically significant over expression of both (P<0.0001) and (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of was more pronounced than . Immunohistochemistry of the patient group showed increased immunoreactivity of at blood-brain barrier and increased reactivity of in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy.
Our results suggested that in association with might be responsible for the multi-drug resistance in epilepsy. and could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.
约30%的癫痫患者对抗癫痫药物无反应，导致难治性癫痫发作。内侧颞叶癫痫（MTLE）耐药的发病机制尚未完全明确。药物外排转运体活性增加可能与之相关，导致药物在靶点部位处于亚临床浓度。主要的药物外排转运体是通透性糖蛋白（）和多药耐药相关蛋白1（）。目前主要的缺陷是在等量的耐药癫痫组织和年龄匹配的非癫痫组织中对转运体进行表达分析。
我们研究了从癫痫手术患者（n = 15）切除的硬化海马组织中的和药物外排转运体，并将其表达谱与从非癫痫尸检病例（n = 15）切除的组织进行比较。
在MTLE病例中，在基因和蛋白水平均发现和有统计学意义的过表达（P < 0.0001）和（P = 0.01）。的变化倍数比更明显。患者组的免疫组织化学显示血脑屏障处的免疫反应性增加，实质中的反应性增加。共聚焦免疫荧光显微镜证实了结果。
我们的结果表明，与可能共同导致癫痫的多药耐药。和可能是抗癫痫药物在脑中生物利用度和组织分布的重要决定因素，可通过药理学抑制以实现药物向靶点部位的最佳渗透。
