Effects of an N-type calcium channel antagonist (SNX 111; Ziconotide) on calcium-45 accumulation following fluid-percussion injury.
Effects of an N-type calcium channel antagonist (SNX 111; Ziconotide) on calcium-45 accumulation following fluid-percussion injury.
复制标题
N 型钙通道拮抗剂（SNX 111；齐考诺肽）对液体冲击损伤后钙 45 积累的影响。
DOI：
10.1089/neu.1999.16.879
复制
发表时间：
1999
影响因子：
4.2
通讯作者：
Hovda,DA
中科院分区：
文献类型：
--
作者：
Samii,A;Badie,H;Fu,K;Luther,RR;Hovda,DA
实验性创伤性脑损伤（TBI）后钙的积累已被证明是一个突出的病理生理学组成部分，可以损害线粒体功能并威胁细胞存活。ω-芋螺肽SNX-111，也称为齐考诺肽，是电压门控N型钙通道的有效拮抗剂，并已证明对缺血诱导的神经元损伤具有显著的神经保护作用。为了确定该化合物是否能有效减少与TBI相关的钙积聚，在中度脑损伤后1小时，对大鼠静脉注射SNX-111（2.2至2.75 atm）侧向液压冲击损伤（或假手术），剂量为1（n= 30）、3（n= 31）或5（n= 30）mg/kg;另一组接受0.9%生理盐水（n= 35）。在损伤后6、12、24、48和96小时处理脑进行钙45（45 Ca）放射自显影。分析了20个皮质和皮质下区域的光密度测量结果。给予生理盐水的损伤动物在损伤部位同侧的12个区域内显示出45 Ca摄取的显著增加。最显著的增加是明显的整个同侧大脑皮层。当在损伤后6、12和48小时测量时，SNX-111以剂量反应方式减少损伤诱导的同侧皮质内的钙积累。这些药物诱导的钙蓄积减少在同侧大脑皮层高达75%，在其他同侧区域（包括丘脑和海马）高达50%。因此，结果表明，创伤后阻断电压门控N型钙通道可减少创伤诱导的钙积累。
Accumulation of calcium following experimental traumatic brain injury (TBI) has been demonstrated to be a prominent pathophysiological component that can compromise mitochondrial functioning and threaten cell survival. The omega-conopeptide SNX-111, also known as Ziconotide, is a potent antagonist of the voltage-gated N-type calcium channel and has demonstrated significant neuroprotective effects against ischemia-induced neuronal injury. To determine whether this compound would be effective in reducing calcium accumulation associated with TBI, SNX-111 was administered intravenously to rats 1 hour following a moderate (2.2 to 2.75 atm) lateral fluid-percussion injury (or sham) at doses of 1 (n= 30), 3 (n= 31), or 5 (n= 30) mg/kg; another group received 0.9% saline solution (n= 35). Brains were processed for calcium 45 (45Ca) autoradiography at 6, 12, 24, 48, and 96 hours following insult. Optical density measurements of 20 cortical and subcortical regions were analyzed. Injured animals administered saline solution exhibited a significant increase in45Ca uptake within 12 regions ipsilateral to the site of injury. The most prominent increases were evident throughout the ipsilateral cerebral cortex. SNX-111 reduced the injury-induced calcium accumulation within the ipsilateral cortex in a dose-response fashion when measured at 6, 12, and 48 hours after insult. These drug-induced reductions in calcium accumulation were as high as 75% in the ipsilateral cerebral cortex, and up to 50% in other ipsilateral regions (including thalamus and hippocampus). Consequently, the results suggest that posttraumatic blocking of the voltage-gated N-type calcium channel after injury reduces prolonged, trauma-induced calcium accumulation.
登录
查看更多内容
昏迷时听觉脑干和中长潜伏期诱发电位。
影响因子：
--
作者：
Rosenberg,C;Wogensen,K;Starr,A
通讯作者：
Starr,A
ω-Conopeptides 对清醒大鼠的心血管作用：作用机制
DOI：
--
发表时间：
1992
期刊：
影响因子：
--
作者：
S. Bowersox;T. Singh;L. Nádasdi;Z. Żukowska;K. Valentino;B. Hoffman
通讯作者：
B. Hoffman
影响因子：
5.3
作者：
B. T. Stokes;P. Fox;G. Hollinden
通讯作者：
G. Hollinden
影响因子：
4.2
作者：
DIETRICH, WD;ALONSO, O;HALLEY, M
通讯作者：
HALLEY, M
Ca(2) 依赖性过程作为神经毒性的介质。
影响因子：
3.4
作者：
M. Verity
通讯作者：
M. Verity