Defence Research and Development Canada, Toronto, Canada.
J Neuroinflammation. 2010 Jan 18;7:5. doi: 10.1186/1742-2094-7-5.
Traumatic brain injury (TBI) initiates interrelated inflammatory and coagulation cascades characterized by wide-spread cellular activation, induction of leukocyte and endothelial cell adhesion molecules and release of soluble pro/antiinflammatory cytokines and thrombotic mediators. Resuscitative care is focused on optimizing cerebral perfusion and reducing secondary injury processes. Hypertonic saline is an effective osmotherapeutic agent for the treatment of intracranial hypertension and has immunomodulatory properties that may confer neuroprotection. This study examined the impact of hypertonic fluids on inflammatory/coagulation cascades in isolated head injury.
Using a prospective, randomized controlled trial we investigated the impact of prehospital resuscitation of severe TBI (GCS < 8) patients using 7.5% hypertonic saline in combination with 6% dextran-70 (HSD) vs 0.9% normal saline (NS), on selected cellular and soluble inflammatory/coagulation markers. Serial blood samples were drawn from 65 patients (30 HSD, 35 NS) at the time of hospital admission and at 12, 24, and 48-h post-resuscitation. Flow cytometry was used to analyze leukocyte cell-surface adhesion (CD62L, CD11b) and degranulation (CD63, CD66b) molecules. Circulating concentrations of soluble (s)L- and sE-selectins (sL-, sE-selectins), vascular and intercellular adhesion molecules (sVCAM-1, sICAM-1), pro/antiinflammatory cytokines [tumor necrosis factor (TNF)-alpha and interleukin (IL-10)], tissue factor (sTF), thrombomodulin (sTM) and D-dimers (D-D) were assessed by enzyme immunoassay. Twenty-five healthy subjects were studied as a control group.
TBI provoked marked alterations in a majority of the inflammatory/coagulation markers assessed in all patients. Relative to control, NS patients showed up to a 2-fold higher surface expression of CD62L, CD11b and CD66b on polymorphonuclear neutrophils (PMNs) and monocytes that persisted for 48-h. HSD blunted the expression of these cell-surface activation/adhesion molecules at all time-points to levels approaching control values. Admission concentrations of endothelial-derived sVCAM-1 and sE-selectin were generally reduced in HSD patients. Circulating sL-selectin levels were significantly elevated at 12 and 48, but not 24 h post-resuscitation with HSD. TNF-alpha and IL-10 levels were elevated above control throughout the study period in all patients, but were reduced in HSD patients. Plasma sTF and D-D levels were also significantly lower in HSD patients, whereas sTM levels remained at control levels.
These findings support an important modulatory role of HSD resuscitation in attenuating the upregulation of leukocyte/endothelial cell proinflammatory/prothrombotic mediators, which may help ameliorate secondary brain injury after TBI.
NCT00878631.
颅脑损伤（TBI）引发广泛细胞激活、白细胞和内皮细胞黏附分子诱导以及可溶性促炎/抗炎细胞因子和血栓形成介质释放的相互关联的炎症和凝血级联反应。复苏治疗的重点是优化脑灌注和减少继发性损伤过程。高渗盐水是治疗颅内高压的有效渗透治疗剂，具有免疫调节特性，可能具有神经保护作用。本研究检查了高渗液对分离性颅脑损伤中炎症/凝血级联的影响。
采用前瞻性、随机对照试验，我们研究了院前复苏严重颅脑损伤（GCS<8）患者时使用 7.5%高渗盐水联合 6%右旋糖酐-70（HSD）与 0.9%生理盐水（NS）对选定的细胞和可溶性炎症/凝血标志物的影响。65 例患者（30 例 HSD，35 例 NS）入院时和复苏后 12、24 和 48 小时抽取系列血样。流式细胞术用于分析白细胞细胞表面黏附（CD62L、CD11b）和脱颗粒（CD63、CD66b）分子。通过酶联免疫吸附试验评估可溶性（s）L-和 sE-选择素（sL-、sE-选择素）、血管和细胞间黏附分子（sVCAM-1、sICAM-1）、促炎/抗炎细胞因子[肿瘤坏死因子（TNF）-α和白细胞介素（IL）-10]、组织因子（sTF）、血栓调节蛋白（sTM）和 D-二聚体（D-D）的循环浓度。25 名健康受试者作为对照组进行研究。
TBI 引起所有患者评估的大多数炎症/凝血标志物发生明显改变。与对照组相比，NS 患者的多形核白细胞（PMN）和单核细胞表面 CD62L、CD11b 和 CD66b 的表达增加了 2 倍，这种表达持续了 48 小时。HSD 在所有时间点均减弱了这些细胞表面激活/黏附分子的表达，使其接近对照值。入院时内皮衍生的 sVCAM-1 和 sE-选择素水平在 HSD 患者中普遍降低。HSD 患者在复苏后 12 和 48 小时，但不是 24 小时，sL-选择素水平显著升高。所有患者在整个研究期间 TNF-α和 IL-10 水平均高于对照，但 HSD 患者的 TNF-α和 IL-10 水平降低。HSD 患者的血浆 sTF 和 D-D 水平也明显较低，而 sTM 水平保持在对照水平。
这些发现支持 HSD 复苏在减轻白细胞/内皮细胞促炎/促血栓形成介质上调方面的重要调节作用，这可能有助于减轻 TBI 后的继发性脑损伤。
NCT00878631。
