Whalen M J, Carlos T M, Kochanek P M, Heineman S
Safar Center for Resuscitation Research, Brain Trauma Research Center, Pittsburgh, PA, USA.
Acta Neurochir Suppl. 1998;71:212-4. doi: 10.1007/978-3-7091-6475-4_61.
Previous studies in our laboratory have shown that controlled cortical impact (CCI) produces an acute inflammatory response in rat brain, including neutrophil accumulation and upregulation of cell adhesion molecules. The purpose of this study was to compare the time course of acute inflammation to blood-brain barrier (BBB) breakdown after (CCI) in rats.
Male Wistar rats (n = 4-7/group) were subjected to CCI (2.5 mm depth, 4 m/s) and injected with Evans-blue dye (2%, 5 ml/kg) at 30 min, 3.5 h, 7.5 h, or 23.5 h after trauma. 30 min after dye injection rats were saline-perfused. BBB permeability was measured by spectrophotometric quantitation of Evans-blue in injured brain. Alternate cryostat sections from the anterior segment of the injured hemisphere were analyzed immunohistochemically for neutrophils (MoAb RP-3 vs rat neutrophils) or E-selectin (MoAb vs E-selectin). Neutrophils and E-selectin-positive blood vessels were quantitated by light microscopy in 100x cortical and hippocampal fields.
BBB breakdown was maximal early after CCI, whereas maximum E-selectin upregulation (8 h) and neutrophil accumulation (24 h) occurred later. Events other than acute inflammation initiate BBB permeability after CCI. Acute inflammation may contribute to BBB permeability at 4 h to 24 h after CCI.
我们实验室之前的研究表明,控制性皮质撞击(CCI)会在大鼠脑中引发急性炎症反应,包括中性粒细胞聚集和细胞黏附分子上调。本研究的目的是比较大鼠CCI后急性炎症与血脑屏障(BBB)破坏的时间进程。
雄性Wistar大鼠(每组n = 4 - 7只)接受CCI(深度2.5 mm,速度4 m/s),并在创伤后30分钟、3.5小时、7.5小时或23.5小时注射伊文思蓝染料(2%,5 ml/kg)。染料注射后30分钟,大鼠用生理盐水灌注。通过分光光度法定量测定损伤脑中的伊文思蓝来测量BBB通透性。对损伤半球前段的交替低温切片进行免疫组织化学分析,检测中性粒细胞(抗大鼠中性粒细胞单克隆抗体RP - 3)或E - 选择素(抗E - 选择素单克隆抗体)。通过光学显微镜在100倍放大的皮质和海马区域定量中性粒细胞和E - 选择素阳性血管。
CCI后早期BBB破坏最大,而E - 选择素上调最大值(8小时)和中性粒细胞聚集最大值(24小时)出现较晚。CCI后引发BBB通透性的是急性炎症以外的事件。急性炎症可能在CCI后4小时至24小时导致BBB通透性增加。