Acute Brain Injury, Mechanisms and Consequences

描述（改编自申请人摘要）：这是一份申请， 支持旨在阐明兴奋性毒性和 发育（围产期）脑损伤中的细胞凋亡机制 与头部创伤和缺氧/缺血有关。除了解决 在申请期间，研究人员已制定了这些目标， 在发育的突触发生期， 短暂的酒精中毒会引发大量的凋亡 神经退行性变，从大脑的许多不同区域删除数百万个神经元。 发育中的大鼠、小鼠或豚鼠的大脑。我们的调查结果表明， 乙醇通过双重机制触发细胞凋亡--阻断NMDA谷氨酸 受体和GABAA受体的过度激活。我们建议， 这些发现可以帮助解释大脑质量减少和终身神经行为障碍。 与人类胎儿酒精综合征（FAS）相关的障碍。 这一发现的重要性被伴随的证据所扩大， 乙醇的神经毒性特性被许多其他药剂所共享， 阻断NMDA谷氨酸受体或激活GABAA受体，其中许多 药物是滥用药物和/或经常用于产科和儿科 药我们发现的一个重要特征是， 突触发生期（大鼠和小鼠出生后前2周， 人类出生后的前几年）不同的神经元 不同的人群对不同的时间模式做出反应， 这些药物的诱导骨质疏松作用。因此，取决于 暴露后，神经元组的不同组合将被删除。

DESCRIPTION (Adapted from applicant's abstract): This is an application to support studies aimed at clarifying the role(s) of excitotoxic and /or apoptotic cell death mechanisms in developmental (perinatal) brain injury associated with head trauma and hypoxia/ischemia. In addition to addressing these aims during the application period, the investigator has made the unanticipated discovery that during the synaptogenesis period of development transient ethanol intoxication triggers a massive wave of apoptotic neurodegeneration, deleting millions of neurons from many different regions of the developing rat, mouse, or guinea pig brain. Our findings document that ethanol triggers apoptosis by a dual mechanism - blockade of NMDA glutamate receptors and excessive activation of GABAA receptors. We propose that our findings can help explain the reduced brain mass and lifelong neurobehavioral disturbances associated with the human fetal alcohol syndrome (FAS). Significance of this discovery is broadened by accompanying evidence that ethanol's neurotoxic properties are shared by numerous other agents that either block NMDA glutamate receptors or activate GABAA receptors, and many of these agents are drugs of abuse and/or are used regularly in obstetric and pediatric medicine. An important feature of our findings is that within the synaptogenesis period (first 2 weeks after birth for rats and mice, but third trimester and first several years after birth for humans) different neuronal populations have different temporal patterns for responding to the apoptosis-inducing effects of these drugs. Thus, depending on the timing of exposure, different combinations of neuronal groups will be deleted.