Bumetanide inhibits rapid kindling in neonatal rats.

Bumetanide inhibits rapid kindling in neonatal rats.
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DOI:
10.1111/j.1528-1167.2009.02048.x
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发表时间:
2009-09
期刊:
影响因子:
5.6
通讯作者:
Sankar R
Sankar R
中科院分区:
医学1区
文献类型:
--
作者:
Mazarati A;Shin D;Sankar R

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目的 研究布美他尼(一种 Na+-K+-2Cl− 协同转运蛋白 (NKCC1) 的选择性阻断剂)对未成熟大鼠海马兴奋性和快速点燃的影响。研究在三个年龄的 Wistar 大鼠中进行:出生后第 11 天(P11,新生儿)、P14(新生儿后)和 P21(青春期前)。研究开始前 20 分钟腹腔内给予布美他尼(0.2、0.5、2.5 mg/kg)。通过测量腹侧海马电刺激引起的后放电阈值和持续时间来检查海马兴奋性。点火程序包括对腹侧海马体进行 80 次电刺激,每 5 分钟进行一次。 P11时,布美他尼(0.5 mg/kg)增加了基线海马后放电阈值并缩短了后放电持续时间。布美他尼延迟了这种情况的发生,减少了点燃过程中完全运动性癫痫发作的次数,并防止了大多数动物因点燃引起的癫痫易感性增强的发展。在 P14 时,布美他尼 (0.5 mg/kg) 没有诱导显着的抗癫痫作用,尽管在部分动物中观察到海马兴奋性受到抑制并抑制点燃。在 P21 时,布美他尼(0.2;2.5 mg/kg)对海马兴奋性和点燃进展没有影响。获得的结果进一步证明布美他尼可能有益于治疗新生儿癫痫发作,并且NKCC1代表了未成熟大脑中抗癫痫干预的潜在靶点。
To examine effects of bumetanide, a selective blocker of Na+-K+-2Cl− cotransporter (NKCC1), on hippocampal excitability and rapid kindling in immature rats. Studies were performed in Wistar rats of three ages: postnatal day 11 (P11, neonatal), P14 (post-neonatal), and P21 (pre-adolescent). Bumetanide (0.2, 0.5, 2.5 mg/kg) was given intraperitoneally 20 minutes prior to the beginning of the studies. Hippocampal excitability was examined by measuring threshold and duration of afterdischarge, which had been elicited by electrical stimulation of ventral hippocampus. Kindling procedure consisted of 80 electrical stimulations of ventral hippocampus, delivered every 5 minutes. At P11, bumetanide (0.5 mg/kg) increased the baseline hippocampal afterdischarge threshold and shortened the afterdischarge duration. Bumetanide delayed the occurrence, and reduced the number of full motor seizures during kindling, and prevented the development of kindling-induced enhanced seizure susceptibility in a majority of animals. At P14 bumetanide (0.5 mg/kg) induced no significant antiepileptic effects, although suppression of hippocampal excitability and inhibition of kindling were observed in a subset of animals. At P21 bumetanide (0.2; 2.5 mg/kg) exerted no effects on hippocampal excitability and kindling progression. The obtained results provide further evidence that bumetanide may be beneficial for treating neonatal seizures, and that NKCC1 represents a potential target for antiepileptic interventions in the immature brain.
DOI: 10.1111/j.1528-1167.2008.01674.x
发表时间: 2008-10-01
期刊: EPILEPSIA
影响因子: 5.6
作者:
Mazarati, Andrey;Wu, Jim;Sankar, Raman
通讯作者: Sankar, Raman
DOI: 10.1016/0165-3806(91)90116-z
发表时间: 1991-07-16
期刊: DEVELOPMENTAL BRAIN RESEARCH
影响因子: --
作者:
MICHELSON, HB;LOTHMAN, EW
通讯作者: LOTHMAN, EW
DOI: 10.1016/j.neuroscience.2004.06.077
发表时间: 2004-01-01
期刊: NEUROSCIENCE
影响因子: 3.3
作者:
Sykov치, E
通讯作者: Sykov치, E
DOI: 10.1016/0013-4694(72)90177-0
发表时间: 1972-01-01
期刊: ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子: --
作者:
RACINE, RJ
通讯作者: RACINE, RJ
DOI: 10.1016/j.neuropharm.2007.06.015
发表时间: 2007-09-01
期刊: NEUROPHARMACOLOGY
影响因子: 4.7
作者:
Kilb, W.;Sinning, A.;Luhmann, H. J.
通讯作者: Luhmann, H. J.