TRAUMATIC BRAIN INJURY NEUROCHEMICAL CONSEQUENCES--MICRODIALYSIS

这个子项目的目的是确定离子流的模式，兴奋性 氨基酸（EAA）释放，以及局灶性和 弥漫性脑损伤 我们使用脑内微透析技术， 测量皮质细胞外液（ECF）的变化， 头部严重受伤后的几天。 这一试点数据显示， 持续增加谷氨酸和天冬氨酸，持续24 在脑挫伤中持续数小时或更长时间。 这EAA释放可能会延续离子 在挫伤组织的周边流动，从而诱导星形胶质细胞 肿胀和恶化的细胞毒性水肿。 创伤模型显示，ECF钾增加（从4到30倍）， 撞击后的第一分钟 伴随的钠内流应该 也因此发生。 我们已经证明了5至15 mmol的增加， ECF钠和伴随的ECF钾减少，4-6小时后， 严重受伤。 这些动态事件可能代表了离子的恢复， 跨膜稳态 先前的研究表明， 泵送可以通过厌氧糖酵解来实现， ECF乳酸增加。 创伤后早期脑血流量（CBF）减少， 我们已经证明， 脑组织的基质。 这可能会导致酸中毒， 乳酸盐增加。 高ICP和低CPP可能会加剧这一原因 EAA发布 ECF中离子紊乱的严重程度和持续时间可能决定ECF中 大量星形胶质细胞肿胀，从而导致ICP升高。 我们的飞行员 研究表明，ECF钠最初上升，钾福尔斯下降，当 ICP稳定或下降。 在CIP不受控制的增加期间， 发生钾外流。 钾外流由星形胶质细胞缓冲 肿胀. 我们将通过磁共振成像来绘制脑水分布图， 以测试离子通量、ICP升高、水肿和 能量代谢状态 我们将测试谷氨酸释放抑制剂和NMDA拮抗剂药物， 温度在这些事件中发生变化。

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.