Neuroprotection by glutamate receptor antagonists against seizure-induced excitotoxic cell death in the aging brain.
Neuroprotection by glutamate receptor antagonists against seizure-induced excitotoxic cell death in the aging brain.
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DOI：
10.1016/j.expneurol.2010.03.013
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发表时间：
2010-07
影响因子：
5.3
通讯作者：
Schauwecker, P. Elyse
中科院分区：
文献类型：
--
作者：
Schauwecker, P. Elyse
我们以前已经确定了两种近交系小鼠对海马神经元损伤诱导的细胞死亡易感性的表型差异。我们还报道了与年龄相关的增加的敏感性神经毒性作用的神经损伤诱导的损伤是调节应变依赖性的方式。在本研究中，我们希望开始，以确定的药理学机制，有助于变化的反应红藻氨酸的神经毒性作用。因此，我们比较了NMDA受体拮抗剂MK-801和AMPA受体拮抗剂NBQX对年轻、中年和老年C57 BL/6和FVB/N小鼠在红藻氨酸诱导癫痫持续状态后90分钟给予红藻氨酸诱导兴奋性毒性细胞死亡的红藻氨酸模型中海马损伤的影响。在红藻氨酸盐注射后，对小鼠的癫痫发作活动进行评分，并在红藻氨酸盐施用后7天处理来自每个年龄和拮抗剂组的小鼠的脑以进行光学显微镜组织病理学评价，以评价癫痫引起的损伤的严重程度。MK-801给药显著降低了年轻、成熟和老年FVB/N小鼠海马损伤的程度，而NBQX的应用仅有效减轻了年轻和老年小鼠所有海马子区域的细胞死亡。我们的研究结果表明，NMDA和非NMDA受体都参与红藻氨酸诱导的细胞死亡的小鼠，并表明，老化可能差异影响神经保护剂的能力，以防止海马损伤。这两种拮抗剂有效性的差异可能是由于对多巴胺能神经递质系统或离子通道特异性的差异调节。
We previously have identified phenotypic differences in susceptibility to hippocampal seizure-induced cell death among two inbred strains of mice. We have also reported that the age-related increased susceptibility to the neurotoxic effects of seizure-induced injury is regulated in a strain-dependent manner. In the present study, we wanted to begin to determine the pharmacological mechanism that contributes to variability in the response to the neurotoxic effects of kainate. Thus, we compared the effects of the NMDA receptor antagonist, MK-801 and of the AMPA receptor antagonist NBQX on hippocampal damage in the kainate model of seizure-induced excitotoxic cell death in young, middle-aged, and aged C57BL/6 and FVB/N mice, when given 90 minutes following kainate-induced status epilepticus. Following kainate injections, mice were scored for seizure activity and brains from mice in each age and antagonist group were processed for light microscopic histopathologic evaluation seven days following kainate administration to evaluate the severity of seizure-induced injury. Administration of MK-801 significantly reduced the extent of hippocampal damage in young, mature and aged FVB/N mice, while application of NBQX was only effective at attenuating cell death in young and aged mice throughout all hippocampal subfields. Our results suggest that both NMDA and non-NMDA receptors are involved in kainate-induced cell death in the mouse and suggest that aging may differentially affect the ability of neuroprotectants to protect against hippocampal damage. Differences in the effectiveness of these two antagonists could result from differential regulation of glutamatergic neurotransmitter systems or ion channel specificity.
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DOI：
10.1002/neu.480230915
发表时间：
1992-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHOI, DW
通讯作者：
CHOI, DW
影响因子：
2.8
作者：
Le, DA;Lipton, SA
通讯作者：
Lipton, SA
影响因子：
2.9
作者：
LALLEMENT, G;DELAMANCHE, IS;BLANCHET, G
通讯作者：
BLANCHET, G
影响因子：
5.6
作者：
CLIFFORD, DB;OLNEY, JW;ZORUMSKI, CF
通讯作者：
ZORUMSKI, CF
影响因子：
2.2
作者：
BERTRAM, EH;LOTHMAN, EW
通讯作者：
LOTHMAN, EW