Khalaf Sherien E, Al Masri Mohammad, Oriquat Ghaleb, Kamel Maher A, Assem Nagwa M, Abdel-Tawab Suzan M, Elblehi Samar S, Mahmoud Shimaa A
Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Department Audiology and Speech Pathology, Al-Ahlyyia Amman University, Amman, Jordan.
Front Mol Neurosci. 2025 Jun 26;18:1613893. doi: 10.3389/fnmol.2025.1613893. eCollection 2025.
Epilepsy is a common neurological disorder; seizures and hyperexcitability are its defining features in the central nervous system (CNS). The condition known as status epilepticus (SE) can be fatal, as it involves seizures occurring. Epilepsy is typically treated with antiepileptic drugs (AEDs) like carbamazepine (CBZ). The present study aimed to establish a rat model of SE-like disease using the LiCl-pilocarpine and then utilize these rat models to evaluate the therapeutic potential of AST and/or CBZ in a solution form or loaded on NLCs via intranasal administration. Additionally, to investigate the potential molecular targets of AST and AST + CBZ-nanoformulations.
After the treatment was completed, the rats underwent behavioral tests, including the rotarod and Morris Water Maze (MWM). They are then sacrificed and their brains were dissected to obtain the cerebral cortex and hippocampus for the assessment of neurotransmitters such as gamma-aminobutyric acid (GABA), serotonin, and dopamine; gene expression of GABA type A (GABAA) receptors subunits and gephyrin; indicators of inflammation like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and High-Mobility Group Box 1 (HMGB1); antioxidant markers, including nuclear factor transcription factor E2-related factor 2 (Nrf2) and hem oxygenase-1 (HO-1).
The rats treated with the combination of AST and CBZ in nano-formulations seeing the best results.
Astaxanthin (AST) may reduce epilepsy-induced oxidative stress and neuronal cell death in the brain. Nano lipid carriers (NLCs) serve as better drug delivery carriers for lipophilic drugs such as CBZ and AST. AST exhibited potential anti-epileptic effects on its own, particularly as NLC-nanoformulations and when combined with conventional AEDs (CBZ).
癫痫是一种常见的神经系统疾病；癫痫发作和中枢神经系统（CNS）的过度兴奋是其主要特征。癫痫持续状态（SE）这一病症可能是致命的，因为它涉及癫痫发作。癫痫通常用卡马西平（CBZ）等抗癫痫药物（AEDs）进行治疗。本研究旨在使用氯化锂-匹鲁卡品建立类癫痫持续状态疾病的大鼠模型，然后利用这些大鼠模型通过鼻内给药评估溶液形式或负载于纳米脂质载体（NLCs）上的虾青素（AST）和/或CBZ的治疗潜力。此外，研究AST和AST + CBZ纳米制剂的潜在分子靶点。
治疗完成后，对大鼠进行行为测试，包括转棒试验和莫里斯水迷宫（MWM）。然后将它们处死并解剖大脑，获取大脑皮层和海马体，以评估神经递质，如γ-氨基丁酸（GABA）、血清素和多巴胺；GABA A型（GABAA）受体亚基和桥连蛋白的基因表达；炎症指标，如活化B细胞核因子κB轻链增强子（NF-κB）和高迁移率族蛋白B1（HMGB1）；抗氧化标志物，包括核因子转录因子E2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）。
纳米制剂形式的AST和CBZ联合治疗的大鼠取得了最佳效果。
虾青素（AST）可能减轻癫痫引起的脑内氧化应激和神经元细胞死亡。纳米脂质载体（NLCs）是CBZ和AST等亲脂性药物更好的药物递送载体。AST自身表现出潜在的抗癫痫作用，特别是作为NLC纳米制剂以及与传统AEDs（CBZ）联合使用时。
