Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.
Age- and sex-dependent susceptibility to phenobarbital-resistant neonatal seizures: role of chloride co-transporters.
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年龄和性别依赖性对苯巴比妥的新生儿癫痫发作的敏感性：氯化物共发作用的作用。
DOI：
10.3389/fncel.2015.00173
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发表时间：
2015
影响因子：
5.3
通讯作者：
Kadam SD
中科院分区：
文献类型：
--
作者：
Kang SK;Markowitz GJ;Kim ST;Johnston MV;Kadam SD
未成熟脑的缺血是新生儿癫痫发作的重要原因。获得性新生儿癫痫发作的时间演变及其对抗惊厥药物的反应非常有趣，因为临床相关性不可靠，一线抗癫痫药物疗效差。电中性氯共转运体KCC 2和NKCC 1的表达和功能影响GABA A激动剂的抗癫痫效应。为了研究缺血诱导的癫痫发作的敏感性和GABAA激动剂苯巴比妥（PB）的疗效，与NKCC 1拮抗剂布美他尼（BTN）作为辅助治疗，我们利用永久性单侧颈动脉结扎产生急性缺血性癫痫发作出生后第7天，10日和12天的CD 1小鼠。结扎后立即进行视频脑电图（EEG）定量评估基线和治疗后癫痫发作负担。检查脑的中风损伤和蛋白质印迹分析，以评估KCC 2和NKCC 1的表达。结扎后急性缺血性癫痫发作的严重程度在P7时最高。PB在P10和P12是有效的抗癫痫药物，但在P7不是。BTN作为辅助治疗失败，在所有年龄测试，并在P10显着减弱PB疗效。在所有年龄段均检测到KCC 2的急性缺血后下调。在P7，男性表现出较高的年龄依赖性癫痫发作的易感性，与显着的发育滞后，他们的KCC 2表达。本研究建立了一种新的PB耐药性癫痫发作的新生小鼠模型，证明了年龄/性别依赖性易感性。KCC 2表达的年龄依赖性特征及其损伤后下调可能是该模型中报告的PB抗性的基础。PB治疗后用低剂量BTN阻断NKCC 1未能改善PB疗效。
Ischemia in the immature brain is an important cause of neonatal seizures. Temporal evolution of acquired neonatal seizures and their response to anticonvulsants are of great interest, given the unreliability of the clinical correlates and poor efficacy of first-line anti-seizure drugs. The expression and function of the electroneutral chloride co-transporters KCC2 and NKCC1 influence the anti-seizure efficacy of GABAA-agonists. To investigate ischemia-induced seizure susceptibility and efficacy of the GABAA-agonist phenobarbital (PB), with NKCC1 antagonist bumetanide (BTN) as an adjunct treatment, we utilized permanent unilateral carotid-ligation to produce acute ischemic-seizures in post-natal day 7, 10, and 12 CD1 mice. Immediate post-ligation video-electroencephalograms (EEGs) quantitatively evaluated baseline and post-treatment seizure burdens. Brains were examined for stroke-injury and western blot analyses to evaluate the expression of KCC2 and NKCC1. Severity of acute ischemic seizures post-ligation was highest at P7. PB was an efficacious anti-seizure agent at P10 and P12, but not at P7. BTN failed as an adjunct, at all ages tested and significantly blunted PB-efficacy at P10. Significant acute post-ischemic downregulation of KCC2 was detected at all ages. At P7, males displayed higher age-dependent seizure susceptibility, associated with a significant developmental lag in their KCC2 expression. This study established a novel neonatal mouse model of PB-resistant seizures that demonstrates age/sex-dependent susceptibility. The age-dependent profile of KCC2 expression and its post-insult downregulation may underlie the PB-resistance reported in this model. Blocking NKCC1 with low-dose BTN following PB treatment failed to improve PB-efficacy.
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DOI：
10.1523/jneurosci.1769-10.2010
发表时间：
2010-09-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dzhala VI;Kuchibhotla KV;Glykys JC;Kahle KT;Swiercz WB;Feng G;Kuner T;Augustine GJ;Bacskai BJ;Staley KJ
通讯作者：
Staley KJ
影响因子：
3.7
作者：
Cleary RT;Sun H;Huynh T;Manning SM;Li Y;Rotenberg A;Talos DM;Kahle KT;Jackson M;Rakhade SN;Berry G;Jensen FE
通讯作者：
Jensen FE
影响因子：
3.3
作者：
Aronica, E.;Boer, K.;Gorter, J. A.
通讯作者：
Gorter, J. A.
DOI：
10.1136/fn.78.1.f70
发表时间：
1998-01-01
影响因子：
4.4
作者：
Evans, D;Levene, M
通讯作者：
Levene, M
影响因子：
8.3
作者：
Jaenisch, Nadine;Witte, Otto W.;Frahm, Christiane
通讯作者：
Frahm, Christiane