The AMPA antagonist NBQX protects thalamic reticular neurons from degeneration following cardiac arrest in rats.
The AMPA antagonist NBQX protects thalamic reticular neurons from degeneration following cardiac arrest in rats.
复制标题
AMPA 拮抗剂 NBQX 可保护大鼠心脏骤停后丘脑网状神经元免受变性。
DOI：
10.1016/0006-8993(95)00344-p
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Patrikios,P
中科院分区：
文献类型：
--
作者：
Ross,DT;Brasko,J;Patrikios,P
丘脑网状（RT）神经元在全脑缺血后选择性易发生变性。退化机制被认为涉及兴奋毒性成分，部分介导的AMPA （α-氨基-3-羟基-5-甲基-4-异恶唑丙酸）型兴奋性氨基酸（EAA）受体在缺血后的持续激活。为了验证这一假设，在心脏骤停10分钟后复苏1、3和6小时，以30 mg/kg剂量给药AMPA型EAA选择性竞争性拮抗剂NBQX（2,3-二羟基-6-硝基-7-磺胺酰基-苯并(F)喹草胺二酮）。NBQX治疗导致幸存的RT神经元增加2倍，从心脏骤停病例的平均密度3.6±0.8 × 103神经元/mm3增加到NBQX治疗组的7.4±1.1 × 103神经元/mm3，这代表41.7%的正常RT神经元群体保留，26.9%的易损RT神经元得到保护。与RT内侧或外侧的神经元亚群相比，RT中央核心的神经元对缺血变性表现出更高的易损性，损失约92%，NBQX对保留的敏感性更高，保留增加460%。停搏后给予NBQX的保护表明，在停搏后持续刺激AMPA受体是RT神经元缺血性变性过程中的重要组成部分。
Thalamic reticular (RT) neurons are selectively vulnerable to degeneration following global ischemia. The degenerative mechanism is thought to involve an excitotoxic component, mediated in part by sustained post-ischemia activation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) type excitatory amino acid (EAA) receptors. In order to test this hypothesis, the selective competitive AMPA type EAA antagonist NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxalinedione) was administered at 30 mg/kg to rats 1, 3, and 6 h after resuscitation from 10 min cardiac arrest. NBQX treatment resulted in a 2-fold increase of spared RT neurons, from a mean density of 3.6 ± 0.8 × 103neurons/mm3in cardiac arrest cases to 7.4 ± 1.1 × 103neurons/mm3in the NBQX treated group, which represents sparing of 41.7% of the normal population of RT neurons, and protection of 26.9% of vulnerable RT neurons. Neurons within the central core of the RT manifest both a higher degree of vulnerability to ischemic degeneration, >92% loss, and a higher sensitivity to sparing following NBQX administration, 460% increased sparing, than neuronal sub-populations in the medial or lateral 1 3 of the RT. Protection by post-arrest administration of NBQX suggests that sustained post-arrest stimulation of AMPA receptors is an important component in the process of ischemic degeneration of RT neurons.