TRAUMATIC BRAIN INJURY NEUROCHEMICAL CONSEQUENCES--MICRODIALYSIS

这一子项目的目的是确定离子通量、兴奋性 氨基酸(EAA)的释放和局部组织代谢 弥漫性脑损伤。我们已经使用脑内微透析来 测量皮质细胞外液(ECF)的变化，最多四次 在严重的头部受伤后的几天。这一试点数据显示了七倍的 谷氨酸和天冬氨酸持续增加，持续24小时 在挫伤的大脑中呆上几个小时或更长时间。这种EAA的释放可能会使离子 挫伤组织周围的流量，从而诱导星形胶质细胞 肿胀和加重的细胞毒性水肿。 创伤模型显示ECF钾增加(从4倍到30倍) 撞击后的第一分钟。伴随的向内钠通量应该是 因此也会发生。我们已经展示了5%到15mmol. ECF钠，以及伴随而来的ECF钾的下降，在4-6小时后 伤势严重。这些动态事件可能代表离子的恢复 跨膜动态平衡。以前的研究表明，离子 泵可通过厌氧糖酵解实现，主要引起 ECF乳酸增加。 创伤后早期脑血流量(CBF)减少 我们已经证明可能会导致能量输送不足 脑组织的底物。这可能会导致酸中毒，并进一步 乳酸的增加。高颅内压和低CPP可能会加剧这一原因 EAA发布。 ECF中离子扰动的严重程度和持续时间可能决定 星形胶质细胞肿胀，从而导致颅内压升高。我们的飞行员 研究表明，ECF钠最初上升，钾下降，当 颅内压稳定或下降。在CIP不受控制的增长期间， 钾离子外流就会发生。星形胶质细胞对钾外流的缓冲作用 肿胀。我们将使用核磁共振成像技术绘制脑水图， 为了测试离子通量、升高的颅内压、水肿和 能量代谢状态。 我们将测试谷氨酸释放抑制剂和NMDA拮抗剂，以及 在这些事件中，温度会发生变化。

This subproject aims to determine the patterns of ionic flux, excitatory amino acid (EAA) release, and local tissue metabolism following focal and diffuse brain injury. We have used intracerebral microdialysis to measure changes in cortical extracellular fluid (ECF), for up to four days after severe head injury. This pilot data has shown a seven-fold sustained increase in glutamate and aspartate, persisting twenty-four hours or more in contused brain. This EAA release may perpetuate ionic flux in the periphery of contused tissue, thus inducing astrocyte swelling and worsening cytotoxic edema. Trauma models show increases in ECF potassium (from 4 to 30-fold) in the first minutes following impact. A concomitant inward sodium flux should also therefore occur. We have demonstrated a 5 to 15 mmol increase in ECF sodium, and a concomitant decrease in ECF potassium, 4-6 hours after severe injury. These dynamic events may represent restoration of ionic homeostasis across membranes. Previous studies have shown that ion pumping may be achieved by anaerobic glycolysis, primarily causing increased ECF lactate. The early post-traumatic reductions in cerebral blood flow (CBF) which we have demonstrated may result in insufficient delivery of energy substrates to cerebral tissue. This may cause acidosis and further increases in lactate. High ICP and low CPP may exacerbate this an cause EAA release. The severity and duration of ionic disturbance in ECF, may determine the amount of astrocyte swelling, and thus lead to raised ICP. Our pilot studies show that ECF sodium initially rises and potassium falls, when ICP is stable or declining. During uncontrolled increases in CIP, potassium efflux occurs. Potassium efflux is buffered by astrocyte swelling. We will use brain water mapping by magnetic resonance imaging, to test the relationships between ionic flux, raised ICP, edema, and energy metabolite status. We will test glutamate release inhibitors and NMDA antagonist drugs, and temperature changes upon these events.