Magnesium as a Neuroprotective Agent for Pediatric TBI

描述（由申请人提供）：总体目标 合作，多机构的项目是提供初步的 后续的全面临床试验所需的信息 严重创伤性脑损伤（TBI）儿童的治疗。本研究 将提供特定药物治疗的儿科安全性数据 （硫酸镁），并证明在儿童中的适用性， 评估这种治疗对神经元的作用的方法 细胞外环境（脑微透析）。镁具有良好的 安全性特征，并正在对成年中风患者进行试点研究， 蛛网膜下腔出血的神经保护潜力。然而， 没有关于其在TBI儿童中的安全性或有效性的数据。脑 微透析正在临床和研究环境中使用， 成人TBI，但尚未用于儿童。以下具体目标 弥补这些差距：1。研究镁对儿童的安全性， 严重的创伤性脑损伤，因此可能会损害大脑 2）检查镁在改变灌注中的短期功效; 继发性脑损伤的分子标志物3）检查的可行性 使用临床结果（功能， 神经心理学和行为测量）以及 在损伤后三个月通过MRI测量结构损伤的严重程度。我们将 在患有糖尿病儿童中实施镁的随机、安慰剂对照试验 需要重症监护和颅内压监测的严重TBI患者。 基于受试者可用性和拟定的入选/排除标准，24 受试者将被随机化。临床要求的颅内压 监测将伴随微透析导管的放置， 调查或基线测量后，研究药物（镁 或安慰剂）将以0.2 mmol/kg的推注给药，随后24小时 输液使用血流动力学变量，将脑灌注压 监测。此外，经颅多普勒速度和脑间质 乳酸盐和丙酮酸盐水平将用于评估对大脑的影响。 灌注。微透析将用于评估脑间质中的 离子镁、离子钙、兴奋性氨基酸和一氧化氮 副产品此外，血液中的镁和钙水平（离子化和 将获得）。多项经验证的心理测量和MRI CNS病变数量和位置的评价将解决特定 目标3.

DESCRIPTION (provided by applicant): The overall objective of this collaborative, multi-institutional project is to provide preliminary information required for subsequent, full-scale clinical trials of novel therapies for children with severe traumatic brain injury (TBI). This study will contribute both pediatric safety data for a specific pharmacotherapy (magnesium sulfate) and demonstrate the applicability in children of novel methods for assessing the effects of such therapy on the neuronal extracellular environment (cerebral microdialysis). Magnesium has a good safety profile and is being tested in pilot studies of adults with stroke and subarachnoid hemorrhage for its neuroprotective potential. There are, however, no data regarding its safety or efficacy in children with TBI. Cerebral microdialysis is being used both clinically and in research settings directed to adult TBI, but has not been used in children. The following Specific Aims address these gaps: 1. to examine the safety of magnesium for children with severe traumatic brain injury and therefore potentially compromised cerebral perfusion; 2) to examine the short-term efficacy of magnesium in modifying molecular markers of secondary brain injury 3) to examine the feasibility of measuring longer-term efficacy using clinical outcomes (functional, neuropsychological, and behavioral measures) as well as indicators of the severity of structural injury by MRI at three months post-injury. We will implement a randomized, placebo-controlled trial of magnesium in children with severe TBI who require intensive care and intracranial pressure monitoring. Based on subject availability with proposed inclusion/exclusion criteria, 24 subjects will be randomized. Clinically-required intracranial pressure monitoring will be accompanied by placement of a microdialysis catheter for research purposes. Following baseline measurements, study drug at (magnesium or placebo) will be administered as a bolus of 0.2 mmol/kg followed by 24-hour infusion. Using hemodynamic variables, cerebral perfusion pressure will be monitored. In addition, transcranial doppler velocities and brain interstitial lactate and pyruvate levels will be used to assess effects on cerebral perfusion. Microdialysis will be used to assess brain interstitial levels of ionized magnesium, ionized calcium, excitatory amino acids, and nitric oxide byproducts. In addition blood magnesium and calcium levels (both ionized and total) will be obtained. Multiple validated psychometric measures and MRI evaluation of CNS lesion numbers and location will address Specific Aim 3.