Johnston M V, Trescher W H, Taylor G A
Johns Hopkins University School of Medicine, Kennedy Krieger Institute, Baltimore, Maryland, USA.
Adv Pediatr. 1995;42:1-45.
Brain damage from severe hypoxemia and ischemia is involved in many childhood disorders that produce permanent disability. Recent progress in diagnosis and brain imaging as well as in the laboratory has expanded understanding of the pathophysiology of these disorders. They are currently thought to trigger a neurotoxic biochemical cascade that produces permanent cell death over a period of hours to days. A prominent feature of this cascade is synaptic dysfunction and overactivation of excitatory amino acid receptors that carry a majority of the excitatory messages transmitted in the brain. In premature infants the periventricular white matter is especially vulnerable, whereas neuronal structures are more vulnerable at term and at older ages. Numerous drugs are now known to protect the brain from neuronal damage in laboratory models. Application of this new pharmacology will require techniques to monitor cerebral metabolism and blood flow at the bedside in order to ensure that only high-risk infants are included. Although the new medications can be expected to have significant adverse effects as well as benefits, it seems likely that this therapy will be applied to certain high-risk groups over the next decade.
严重低氧血症和缺血导致的脑损伤与许多导致永久性残疾的儿童疾病有关。诊断、脑成像以及实验室方面的最新进展拓宽了对这些疾病病理生理学的认识。目前认为，它们会引发一种神经毒性生化级联反应，在数小时至数天的时间内导致永久性细胞死亡。这种级联反应的一个突出特征是突触功能障碍以及兴奋性氨基酸受体的过度激活，这些受体传递大脑中大部分的兴奋性信息。在早产儿中，脑室周围白质特别脆弱，而在足月儿及更大年龄时，神经元结构更易受损。现在已知许多药物在实验室模型中可保护大脑免受神经元损伤。应用这种新的药理学将需要在床边监测脑代谢和血流的技术，以确保只纳入高危婴儿。尽管新药物可能会有显著的副作用和益处，但在未来十年内，这种疗法似乎有可能应用于某些高危群体。
