Differential regulation of K+-Cl− cotransporter 2 (KCC2) and Na+-K+-Cl− cotransporter 1 (NKCC1) expression by zolpidem in CA1 and CA3 hippocampal subregions of the lithium-pilocarpine status epilepticus rat model

Othman, Muhammad Zulfadhli and Mohd Nasir, Mohd Hamzah and Wan Ahmad, Wan Amir Nizam and Abdullah, Jafri Malin and Che Has, Ahmad Tarmizi (2025) Differential regulation of K+-Cl− cotransporter 2 (KCC2) and Na+-K+-Cl− cotransporter 1 (NKCC1) expression by zolpidem in CA1 and CA3 hippocampal subregions of the lithium-pilocarpine status epilepticus rat model. Experimental Animals, 74 (2). pp. 286-299. ISSN 1341-1357 E-ISSN 1881-7122

PDF - Published Version Download (16MB)

Abstract

Status epilepticus is linked to cognitive decline due to damage to the hippocampus, a key structure involved in cognition. The hippocampus’s high vulnerability to epilepsy-related damage is the main reason for this impairment. Convulsive seizures, such as those observed in status epilepticus, can cause various hippocampal pathologies, including inflammation, abnormal neurogenesis, and neuronal death. Interestingly, substantial evidence points to the therapeutic potential of the sedative/hypnotic agent zolpidem for neurorehabilitation in brain injury patients, following the unexpected discovery of its paradoxical awakening effect. In this study, we successfully established an ideal lithium-pilocarpine rat model of status epilepticus, which displayed significant deficits in hippocampal-dependent learning and memory. The Morris water maze test was used to assess zolpidem’s potential to improve learning and memory, as well as its impact on anxiety-like behavior and motor function. Immunohistochemical staining and fluorescence analysis were used to examine the effect of zolpidem on K+-Cl− cotransporter 2 (KCC2) and Na+-K+-Cl− cotransporter 1 (NKCC1) protein expression in the hippocampal CA1 and CA3. Our findings showed that zolpidem did not improve learning and memory in status epilepticus rats. Additionally, its sedative/hypnotic effects were not apparent in the status epilepticus condition. However, immunohistochemical results revealed that zolpidem significantly restored altered NKCC1 levels in the CA1 and CA3 to levels similar to those seen in normal rats. These findings suggest that zolpidem may contribute to molecular restoration, particularly through its impact on NKCC1 protein expression in the hippocampus, which is crucial for proper inhibitory neurotransmission in the brain

Item Type:	Article (Journal)
Uncontrolled Keywords:	hippocampus, K+-Cl− cotransporter 2 (KCC2), Na+-K+-Cl− cotransporter 1 (NKCC1), status epilepticus, zolpidem
Subjects:	Q Science > QL Zoology
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Science > Department of Biotechnology
Depositing User:	Dr Mohd Hamzah Mohd Nasir
Date Deposited:	02 Oct 2025 17:06
Last Modified:	02 Oct 2025 17:06
URI:	http://irep.iium.edu.my/id/eprint/123533

Actions (login required)

View Item