• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

用电压门控性钠通道阻滞剂进行治疗后可减轻海藻酸诱导的大鼠原代海马神经元凋亡。

Post-treatment with voltage-gated Na(+) channel blocker attenuates kainic acid-induced apoptosis in rat primary hippocampal neurons.

作者信息

Das Arabinda, McDowell Misty, O'Dell Casey M, Busch Megan E, Smith Joshua A, Ray Swapan K, Banik Naren L

机构信息

Department of Neurosciences, Medical University of South Carolina, 96 Jonathan Lucus Street, Charleston, SC 29425, USA.

出版信息

Neurochem Res. 2010 Dec;35(12):2175-83. doi: 10.1007/s11064-010-0321-1. Epub 2010 Dec 3.

DOI:10.1007/s11064-010-0321-1
PMID:21127971
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3954598/
Abstract

Injection of rats with kainic acid (KA), a non-N-methyl-D-aspartate (NMDA) type glutamate receptor agonist, induces recurrent (delayed) convulsive seizures and subsequently hippocampal neurodegeneration, which is reminiscent of human epilepsy. The protective effect of anti-epileptic drugs on seizure-induced neuronal injury is well known; however, molecular basis of this protective effect has not yet been elucidated. In this study, we investigated the effect and signaling mediators of voltage-gated Na(+) channel blockers (Lamotrigine, Rufinamide, Oxcarbazepine, Valproic Acid, and Zonisamide) on KA-induced apoptosis in rat primary hippocampal neurons. Exposure of hippocampal neurons to 10 μM KA for 24 h caused significant increases in morphological and biochemical features of apoptosis, as determined by Wright staining and ApopTag assay, respectively. Analyses showed increases in expression and activity of cysteine proteases, production of reactive oxygen species (ROS), intracellular free [Ca(2+)], and Bax:Bcl-2 ratio during apoptosis. Cells exposed to KA for 15 min were then treated with Lamotrigine, Rufinamide, Oxcarbazepine, Valproic Acid, or Zonisamide. Post-treatment with one of these anti-epileptic drugs (500 nM) attenuated production of ROS and prevented apoptosis in hippocampal neurons. Lamotrigine, Rufinamide, and Oxcarbazepine appeared to be less protective when compared with Valproic Acid or Zonisamide. This difference may be due to blockade of T-type Ca(2+) channels also by Valproic Acid and Zonisamide. Our findings thus suggest that the anti-epileptic drugs that block both Na(+) channels and Ca(2+) channels are significantly more effective than agents that block only Na(+) channels for attenuating seizure-induced hippocampal neurodegeneration.

摘要

给大鼠注射红藻氨酸(KA),一种非N - 甲基 - D - 天冬氨酸(NMDA)型谷氨酸受体激动剂,会诱发反复(延迟)惊厥性癫痫发作,随后导致海马神经变性,这与人类癫痫相似。抗癫痫药物对癫痫发作诱导的神经元损伤的保护作用是众所周知的;然而,这种保护作用的分子基础尚未阐明。在本研究中,我们研究了电压门控钠通道阻滞剂(拉莫三嗪、卢非酰胺、奥卡西平、丙戊酸和唑尼沙胺)对KA诱导的大鼠原代海马神经元凋亡的影响及信号转导介质。分别通过瑞氏染色和ApopTag检测法确定,将海马神经元暴露于10 μM KA 24小时会导致凋亡的形态学和生化特征显著增加。分析表明,凋亡过程中半胱氨酸蛋白酶的表达和活性增加、活性氧(ROS)生成、细胞内游离[Ca²⁺]以及Bax:Bcl - 2比值增加。然后将暴露于KA 15分钟的细胞用拉莫三嗪、卢非酰胺、奥卡西平、丙戊酸或唑尼沙胺处理。用这些抗癫痫药物之一(500 nM)进行后处理可减少ROS生成并防止海马神经元凋亡。与丙戊酸或唑尼沙胺相比,拉莫三嗪、卢非酰胺和奥卡西平的保护作用似乎较小。这种差异可能是由于丙戊酸和唑尼沙胺也阻断了T型钙通道。因此,我们的研究结果表明,对于减轻癫痫发作诱导的海马神经变性,同时阻断钠通道和钙通道的抗癫痫药物比仅阻断钠通道的药物显著更有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/65cbef481674/nihms558543f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/94ecf3b79645/nihms558543f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/5f6c68443a32/nihms558543f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/9211d0a40589/nihms558543f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/5ab9d7929a8c/nihms558543f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/65cbef481674/nihms558543f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/94ecf3b79645/nihms558543f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/5f6c68443a32/nihms558543f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/9211d0a40589/nihms558543f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/5ab9d7929a8c/nihms558543f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2cc/3954598/65cbef481674/nihms558543f5.jpg

相似文献

1
Post-treatment with voltage-gated Na(+) channel blocker attenuates kainic acid-induced apoptosis in rat primary hippocampal neurons.用电压门控性钠通道阻滞剂进行治疗后可减轻海藻酸诱导的大鼠原代海马神经元凋亡。
Neurochem Res. 2010 Dec;35(12):2175-83. doi: 10.1007/s11064-010-0321-1. Epub 2010 Dec 3.
2
Effects of ion channel blockade on the distribution of Na, K, Ca and other elements in oxygen-glucose deprived CA1 hippocampal neurons.离子通道阻断对氧糖剥夺海马CA1区神经元中钠、钾、钙及其他元素分布的影响。
Neuroscience. 2001;103(4):971-83. doi: 10.1016/s0306-4522(01)00035-5.
3
Anthocyanins protect against kainic acid-induced excitotoxicity and apoptosis via ROS-activated AMPK pathway in hippocampal neurons.花青素通过活性氧激活的AMPK途径保护海马神经元免受海藻酸诱导的兴奋性毒性和细胞凋亡。
CNS Neurosci Ther. 2014 Apr;20(4):327-38. doi: 10.1111/cns.12218. Epub 2014 Jan 7.
4
Inhibition of calpain and caspase-3 prevented apoptosis and preserved electrophysiological properties of voltage-gated and ligand-gated ion channels in rat primary cortical neurons exposed to glutamate.抑制钙蛋白酶和半胱天冬酶-3可防止大鼠原代皮层神经元暴露于谷氨酸时发生凋亡,并保留电压门控和配体门控离子通道的电生理特性。
Neuroscience. 2006 May 12;139(2):577-95. doi: 10.1016/j.neuroscience.2005.12.057. Epub 2006 Feb 28.
5
The PI3K/Akt and ERK1/2 signaling pathways mediate the erythropoietin-modulated calcium influx in kainic acid-induced epilepsy.PI3K/Akt和ERK1/2信号通路介导了在 kainic 酸诱导的癫痫中促红细胞生成素调节的钙内流。
Neuroreport. 2013 Apr 17;24(6):335-41. doi: 10.1097/WNR.0b013e32835ffe03.
6
17beta-estradiol attenuates glutamate-induced apoptosis and preserves electrophysiologic function in primary cortical neurons.17β-雌二醇可减轻谷氨酸诱导的原代皮质神经元凋亡并维持其电生理功能。
J Neurosci Res. 2004 Jun 1;76(5):688-96. doi: 10.1002/jnr.20124.
7
Dexmedetomidine protects neurons from kainic acid-induced excitotoxicity by activating BDNF signaling.右美托咪定通过激活脑源性神经营养因子信号通路保护神经元免受海人酸诱导的兴奋性毒性。
Neurochem Int. 2019 Oct;129:104493. doi: 10.1016/j.neuint.2019.104493. Epub 2019 Jun 18.
8
Vitamin D protects against hippocampal apoptosis related with seizures induced by kainic acid and pentylenetetrazol in rats.维生素D可保护大鼠免受与海藻酸和戊四氮诱导的癫痫发作相关的海马细胞凋亡。
Epilepsy Res. 2019 Jan;149:107-116. doi: 10.1016/j.eplepsyres.2018.12.005. Epub 2018 Dec 15.
9
Seizures and neurodegeneration induced by 4-aminopyridine in rat hippocampus in vivo: role of glutamate- and GABA-mediated neurotransmission and of ion channels.4-氨基吡啶在大鼠海马体内诱导的癫痫发作和神经退行性变:谷氨酸和γ-氨基丁酸介导的神经传递及离子通道的作用
Neuroscience. 2000;101(3):547-61. doi: 10.1016/s0306-4522(00)00400-0.
10
NA+, K+-ATPase activity in the brain of the rats with kainic acid-induced seizures: influence of lamotrigine.海人酸诱导癫痫大鼠脑内的钠钾-ATP酶活性:拉莫三嗪的影响
Psychiatr Danub. 2008 Sep;20(3):269-76.

引用本文的文献

1
Oxidative stress and inflammation in the pathogenesis of neurological disorders: Mechanisms and implications.氧化应激与炎症在神经疾病发病机制中的作用:机制与影响
Acta Pharm Sin B. 2025 Jan;15(1):15-34. doi: 10.1016/j.apsb.2024.10.004. Epub 2024 Oct 16.
2
Impact of LITAF on Mitophagy and Neuronal Damage in Epilepsy via MCL-1 Ubiquitination.LITAF通过MCL-1泛素化对癫痫中自噬性线粒体的清除及神经元损伤的影响
CNS Neurosci Ther. 2025 Jan;31(1):e70191. doi: 10.1111/cns.70191.
3
Efficacy of Lacosamide and Rufinamide as Adjuncts to Midazolam-Ketamine Treatment Against Cholinergic-Induced Status Epilepticus in Rats.拉科酰胺和鲁非尼胺作为咪达唑仑-氯胺酮治疗对大鼠胆碱能诱导癫痫持续状态的辅助治疗的疗效。
J Pharmacol Exp Ther. 2024 Jan 17;388(2):347-357. doi: 10.1124/jpet.123.001789.
4
The inhibition of PGAM5 suppresses seizures in a kainate-induced epilepsy model mitophagy reduction.PGAM5的抑制通过减少线粒体自噬抑制红藻氨酸诱导的癫痫模型中的癫痫发作。
Front Mol Neurosci. 2022 Dec 22;15:1047801. doi: 10.3389/fnmol.2022.1047801. eCollection 2022.
5
Rufinamide, a Triazole-Derived Antiepileptic Drug, Stimulates Ca-Activated K Currents While Inhibiting Voltage-Gated Na Currents.鲁非尼酰胺,一种三氮唑衍生的抗癫痫药物,在抑制电压门控钠电流的同时刺激钙激活钾电流。
Int J Mol Sci. 2022 Nov 8;23(22):13677. doi: 10.3390/ijms232213677.
6
A review for the pharmacological effects of paeoniflorin in the nervous system.芍药苷在神经系统中的药理作用综述。
Front Pharmacol. 2022 Aug 15;13:898955. doi: 10.3389/fphar.2022.898955. eCollection 2022.
7
Attenuated succinate accumulation relieves neuronal injury induced by hypoxia in neonatal mice.减弱的琥珀酸积累减轻新生小鼠缺氧诱导的神经元损伤。
Cell Death Discov. 2022 Mar 28;8(1):138. doi: 10.1038/s41420-022-00940-7.
8
Ions, the Movement of Water and the Apoptotic Volume Decrease.离子、水的运动与凋亡性体积减小
Front Cell Dev Biol. 2020 Nov 25;8:611211. doi: 10.3389/fcell.2020.611211. eCollection 2020.
9
Succinate accumulation induces mitochondrial reactive oxygen species generation and promotes status epilepticus in the kainic acid rat model.琥珀酸积累诱导线粒体活性氧产生,并促进海人酸大鼠模型的癫痫持续状态。
Redox Biol. 2020 Jan;28:101365. doi: 10.1016/j.redox.2019.101365. Epub 2019 Oct 31.
10
Vitamin A bio-modulates apoptosis via the mitochondrial pathway after hypoxic-ischemic brain damage.维生素 A 通过缺氧缺血性脑损伤后的线粒体途径对细胞凋亡进行生物调节。
Mol Brain. 2018 Mar 13;11(1):14. doi: 10.1186/s13041-018-0360-0.

本文引用的文献

1
Sinapic acid attenuates kainic acid-induced hippocampal neuronal damage in mice.咖啡酸抑制鼠海马区神经元损伤。
Neuropharmacology. 2010 Jul-Aug;59(1-2):20-30. doi: 10.1016/j.neuropharm.2010.03.012. Epub 2010 Apr 2.
2
Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders.电压门控钠离子通道在癫痫和其他神经紊乱中的治疗靶点。
Lancet Neurol. 2010 Apr;9(4):413-24. doi: 10.1016/S1474-4422(10)70059-4.
3
The inhibition of apoptosis by melatonin in VSC4.1 motoneurons exposed to oxidative stress, glutamate excitotoxicity, or TNF-alpha toxicity involves membrane melatonin receptors.褪黑素通过其膜受体抑制氧化应激、谷氨酸兴奋性毒性或 TNF-α 毒性作用下 VSC4.1 运动神经元凋亡
J Pineal Res. 2010 Mar;48(2):157-69. doi: 10.1111/j.1600-079X.2009.00739.x. Epub 2010 Jan 17.
4
An update on peptide drugs for voltage-gated calcium channels.
Recent Pat CNS Drug Discov. 2010 Jan;5(1):14-22. doi: 10.2174/157488910789753558.
5
Primary Culture of Hippocampal Neurons from P0 Newborn Rats.新生P0大鼠海马神经元的原代培养
J Vis Exp. 2008 Sep 29(19):895. doi: 10.3791/895.
6
Stress, the hippocampus, and epilepsy.压力、海马体与癫痫
Epilepsia. 2009 Apr;50(4):586-97. doi: 10.1111/j.1528-1167.2008.01902.x. Epub 2008 Nov 19.
7
Seizures, antiepileptics, antioxidants and oxidative stress: an insight for researchers.癫痫发作、抗癫痫药、抗氧化剂与氧化应激:给研究人员的启示
Expert Opin Pharmacother. 2008 Dec;9(18):3169-77. doi: 10.1517/14656560802568230.
8
Neurologic damage and neurocognitive dysfunction in urea cycle disorders.尿素循环障碍中的神经损伤和神经认知功能障碍。
Semin Pediatr Neurol. 2008 Sep;15(3):132-9. doi: 10.1016/j.spen.2008.05.007.
9
Development of spontaneous seizures after experimental status epilepticus: implications for understanding epileptogenesis.实验性癫痫持续状态后自发性癫痫发作的发展:对理解癫痫发生的意义。
Epilepsia. 2007;48 Suppl 5:157-63. doi: 10.1111/j.1528-1167.2007.01304.x.
10
The neurobiology of epilepsy.癫痫的神经生物学
Curr Neurol Neurosci Rep. 2007 Jul;7(4):348-54. doi: 10.1007/s11910-007-0053-z.