The double-edged role of nitric oxide in brain function and superoxide-mediated injury.
The double-edged role of nitric oxide in brain function and superoxide-mediated injury.
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发表时间：
1991
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通讯作者：
J. Beckman
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作者：
J. Beckman
胎儿缺血或缺氧可导致脑瘫、智力低下和癫痫。我们认为，脑缺血或缺氧再灌注时神经元产生的一氧化氮和氧自由基可能有助于脑损伤。缺血将使神经元膜脱髓鞘，引起兴奋性神经递质谷氨酸的突触放电，这又打开电压依赖性的N-甲基-D-天冬氨酸特异性谷氨酸受体/离子载体，使钙在神经元中积聚。钙反过来激活氧依赖性神经元一氧化氮合成酶，当氧气通过再灌注重新进入大脑时，该合成酶氧化精氨酸以产生一氧化氮（.NO）。一氧化氮与也由再灌注产生的氧自由基超氧化物（O2-）反应，形成过氧亚硝酸盐（ONOO-）。过氧亚硝酸盐在分解之前可以扩散几微米，形成强大的细胞毒性氧化剂羟基自由基和二氧化氮。这一假说与谷氨酸拮抗剂和氧自由基清除剂限制局灶性缺血后脑梗死的保护作用的现有证据一致。
Fetal ischemia or hypoxia can lead to cerebral palsy, mental retardation and epilepsy. We propose that the production of nitric oxide and oxygen radicals by neurons when ischemic or hypoxic brain is reperfused may contribute to cerebral injury. Ischemia will depolarize neuronal membranes causing the synaptic discharge of the excitatory neurotransmitter glutamate, which in turn opens the voltage-dependent, N-methyl-D-aspartic acid-specific glutamate receptor/ionophore, allowing calcium to accumulate in the neuron. Calcium in turn activates an oxygen-dependent neuronal nitric oxide synthetase, which oxidizes arginine to produce nitric oxide (.NO) when oxygen is readmitted to brain by reperfusion. Nitric oxide reacts with the oxygen radical superoxide (O2-), also produced by reperfusion, to form peroxynitrite (ONOO-). Peroxynitrite can diffuse for several micrometers before decomposing to form the powerful and cytotoxic oxidants hydroxyl radical and nitrogen dioxide. The hypothesis is consistent with available evidence on the protective action of glutamate antagonists and of oxygen radical scavengers for limiting cerebral infarction following focal ischemia.