Adelson P D, Whalen M J, Kochanek P M, Robichaud P, Carlos T M
Department of Neurosurgery and Anesthesiology/Critical Care Medicine, Children's Hospital of Pittsburgh, PA, USA.
Acta Neurochir Suppl. 1998;71:104-6. doi: 10.1007/978-3-7091-6475-4_31.
We sought to investigate the course and magnitude of blood brain barrier (BBB) permeability following focal and diffuse traumatic brain injury (TBI) in immature rats and examine the time course of markers of acute inflammation (neutrophil accumulation and E-selectin [E-sel] expression) following these two types of injury. We measured BBB permeability using i.v. injection Evans Blue (EB) and the extent of inflammation using immunohistochemical techniques identifying neutrophils (monoclonal antibody RP-3) and the endothelial adhesion molecule, E-selectin. Male Sprague-Dawley immature (17 day-old) rats (30-45 g, n = 80) were subjected to a controlled cortical impact (CCI: 2 mm, 4 m/s), a closed head diffuse injury (DI: 150 g/2m) or a corresponding sham procedure (with or without craniotomy). EB was injected i.v. at 30 min before sacrifice, which occurred at 1 h, 4 h, or 24 h after injury. BBB permeability was observed in both the CCI and DI rats at 1 h after injury which largely resolved by 24 h. In the CCI, EB extravasation was seen within and around the contusion. In DI, diffuse BBB permeability was seen. DI was not associated with acute inflammation since there was neither neutrophil accumulation nor E-selectin expression. The CCI rats though had 5.1 +/- 2.2 neutrophils/hpf and 3.0 +/- 0.4 endothelial cells/hpf expressing E-selectin (mean +/- SEM) (both p < 0.05 vs sham and DI). These data suggest that BBB breakdown occurs in the immature rat after both focal and diffuse TBI. This early BBB permeability was not associated with acute inflammation in DI but was in CCI. These data also suggest that contusion is a key factor in the development of a traditional acute inflammatory response after TBI in the immature rat.
我们试图研究未成熟大鼠局灶性和弥漫性创伤性脑损伤（TBI）后血脑屏障（BBB）通透性的过程和程度，并检查这两种类型损伤后急性炎症标志物（中性粒细胞积聚和E-选择素[E-sel]表达）的时间进程。我们通过静脉注射伊文思蓝（EB）测量BBB通透性，并使用免疫组织化学技术鉴定中性粒细胞（单克隆抗体RP-3）和内皮粘附分子E-选择素，以确定炎症程度。雄性Sprague-Dawley未成熟（17日龄）大鼠（30-45克，n = 80）接受控制性皮质撞击（CCI：2毫米，4米/秒）、闭合性头部弥漫性损伤（DI：150克/2米）或相应的假手术（有或无开颅手术）。在处死前30分钟静脉注射EB，处死时间为损伤后1小时、4小时或24小时。损伤后1小时在CCI和DI大鼠中均观察到BBB通透性，到24小时时基本恢复。在CCI中，在挫伤部位及其周围可见EB外渗。在DI中，可见弥漫性BBB通透性。DI与急性炎症无关，因为既没有中性粒细胞积聚也没有E-选择素表达。然而，CCI大鼠每高倍视野有5.1±2.2个中性粒细胞和3.0±0.4个表达E-选择素的内皮细胞（平均值±标准误）（与假手术组和DI组相比，两者p均<0.05）。这些数据表明，在未成熟大鼠中，局灶性和弥漫性TBI后都会发生BBB破坏。这种早期BBB通透性在DI中与急性炎症无关，但在CCI中有关。这些数据还表明，挫伤是未成熟大鼠TBI后传统急性炎症反应发展的关键因素。
