Ferriero D M, Arcavi L J, Sagar S M, McIntosh T K, Simon R P
Department of Neurology, University of California, San Francisco.
Ann Neurol. 1988 Nov;24(5):670-6. doi: 10.1002/ana.410240512.
Excitatory amino acids have been implicated in ischemic neuronal injury. To test this hypothesis in neonatal hypoxia-ischemia, lesions of the cortex and striatum were induced in 7-day-old rats by unilaterally ligating their carotid arteries and subjecting them to hypoxic conditions for 2 hours. Brains examined 1 week later demonstrated, within the regions of ischemic damage, a striking preservation of neurons that stained histochemically for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity. Concentrations of the neuropeptides somatostatin and neuropeptide Y, which colocalize in neurons containing NADPH-d, were unaffected in the areas of ischemic damage. The same pattern of injury with sparing of NADPH-d-reactive neurons was reproduced by focal microinfusion of the excitotoxin quinolinic acid, an endogenous N-methyl-d-aspartate (NMDA) agonist, into the striatum. These results support the hypothesis that neonatal hypoxic-ischemic injury is mediated through excitatory transmitters acting at the NMDA receptor and that the NADPH-d-reactive neurons in the neonate are resistant to excitotoxic damage. This pattern of cell vulnerability is unique to the developing striatum and may relate to the distinct pathological appearance of the basal ganglia that follows neonatal asphyxia.
兴奋性氨基酸与缺血性神经元损伤有关。为了在新生儿缺氧缺血模型中验证这一假说，对7日龄大鼠单侧结扎颈动脉并使其处于缺氧状态2小时，诱导其皮质和纹状体损伤。1周后检查大脑发现，在缺血损伤区域内，对烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d）活性进行组织化学染色的神经元有显著保留。与含NADPH-d的神经元共定位的神经肽生长抑素和神经肽Y的浓度在缺血损伤区域未受影响。通过向纹状体内局部微量注射兴奋性毒素喹啉酸（一种内源性N-甲基-D-天冬氨酸（NMDA）激动剂），再现了同样的损伤模式，即NADPH-d反应性神经元未受损伤。这些结果支持了以下假说：新生儿缺氧缺血性损伤是通过作用于NMDA受体的兴奋性递质介导的，并且新生儿中的NADPH-d反应性神经元对兴奋性毒性损伤具有抗性。这种细胞易损性模式是发育中的纹状体所特有的，可能与新生儿窒息后基底神经节的独特病理表现有关。
