PHYSIOLOGIC RESPONSE TO OSMOTIC THERAPY IN BRAIN EDEMA

急性脑损伤并发质量效应，这是继发性损伤的主要原因，因为它严重降低了脑灌注压或产生了组织移位，从而可能导致脑突出。虽然这种集体效应的病因和机制可能会因临床情况的不同而有很大不同，但治疗选择有限。传统上，渗透剂一直是使用甘露醇和最近的高渗盐水溶液进行医疗治疗的主要手段。尽管有大量的研究和甘露醇的普遍使用，但关于其作用机制(是否减少脑血容量[CBV]或脑含水量)，2)对正常和异常脑的区别作用，3)对脑血流量(CBF)和氧代谢(CMRO2)的影响，4)随着时间的推移失去疗效，以及 5)吸收到受损的脑内，可能导致“反弹性水肿”。部分出于这些担忧，高渗盐水(HS)已被引入作为替代药物；然而，与甘露醇相比，其生理效应和临床疗效尚不清楚。要最佳地使用这些渗透剂来治疗脑肿胀，需要详细了解它们在临床条件下对人体的生理影响。为此，我们将实施以下具体目标：1)测量单次甘露醇或HS(23.4%)对创伤性脑损伤(TBI)和大面积脑梗塞(LHI)患者局部CBF、CMRO2、CBV的影响。我们将使用正电子发射计算机断层扫描技术，在等渗量(5.49mOsm/kg)甘露醇(1.0gm/kg)或HS(0.686 ml/kg)给药前后，对10例LHI、中线移位和10例重型颅脑损伤患者的脑血流量、CBV和CMRO2进行测定；2)测量单次甘露醇或HS(23.4%)对脑损伤患者局部脑体积的影响 利希。在20名患者中，我们将使用MRI测量在AIM 1中使用相同剂量的甘露醇和HS前后脑体积的局部变化。由于颅脑损伤患者的MRI不兼容，我们将不对其进行研究；3)测量接受渗透治疗的脑损伤和LHI患者甘露醇跨越血脑屏障的程度。在每个实体的15名患者中，我们将使用PET和碳-11标记的甘露醇来测量血液：甘露醇的脑渗透性。

Acute brain injury is complicated by mass effect, a major cause of secondary injury by critically reducing cerebral perfusion pressure or producing tissue shifts which can lead to herniation. While the etiology and mechanisms responsible for this mass effect may differ considerably depending on the clinical condition, treatment options are limited. Traditionally osmotic agents have been the mainstay of medical treatment employing mannitol and recently hypertonic saline solutions. Despite numerous investigations and mannitors ubiquitous use, considerable controversy persists regarding its 1) mechanism of action (whether it reduces cerebral blood volume [CBV] or brain water), 2) differential effect in normal and abnormal brain, 3) effect on cerebral blood flow (CBF) and oxygen metabolism (CMRO2), 4) loss of efficacy over time, and 5) uptake into injured brain, which could lead to "rebound edema." In part because of some of these concerns, hypertonic saline (HS) has been introduced as an alternative agent; however, its physiologic effect and clinical efficacy compared to mannitol is unknown. Optimal use of these osmotic agents to treat brain swelling requires a detailed knowledge of their physiological effects in human subjects under the clinical conditions in which they are used. To this end, we will carry out the following Specific Aims: 1) measure the effect of a single bolus of mannitol or HS (23.4%) on regional CBF, CMRO2, CBV in patients with traumatic brain injury (TBI) and large hemispheric infarctions (LHI). We will measure CBF, CBV and CMRO2 using PET before and after a bolus of equi-osmolar (5.49 mOsm/kg ) doses of mannitol (1.0 gm/kg ) or HS (0.686 ml/kg), in 10 patients each with LHI and midline shift and 10 patients each with severe TBI; 2) measure the effect of a single bolus of mannitol or HS (23.4%) on regional brain volume in patients with LHI. In 20 patients we will measure regional change in brain volume using MRI before and after the same doses of mannitol and HS used in Aim 1. TBI patients will not be studied due to the MRI incompatibility of ICP monitors; 3) measure the extent that mannitol crosses the blood-brain-barrier in patients with TBI and LHI receiving osmotic therapy. In 15 patients with each entity we will measure blood: brain permeability of mannitol using PET and carbon-11 labeled-mannitol.