Endothelin and the neurovascular unit in pediatric traumatic brain injury.
Endothelin and the neurovascular unit in pediatric traumatic brain injury.
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DOI：
10.1179/016164111x12881719352138
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发表时间：
2011-03
影响因子：
1.9
通讯作者：
Raghupathi R
中科院分区：
文献类型：
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作者：
Armstead WM;Raghupathi R
本研究表征了新生猪流体冲击脑损伤后内皮素-1、脑血流动力学和组织病理学之间的关系。在配备封闭颅窗的新生猪中诱发侧向液体冲击损伤。用放射性标记微球测定脑血流量，并用放射免疫测定法测定脑脊液内皮素-1。液体冲击损伤后 8 小时，脑脊液内皮素-1 从 26 ± 4 增加至 296 ± 37 pg/ml (~10−10M)。使用内皮素-1拮抗剂BQ-123（1 mg/kg，静脉注射）进行损伤后治疗（30分钟），可阻断局部内皮素-1（~10−10M）的软脑膜动脉血管收缩，并减弱流体冲击损伤引起的脑血流量减少，在损伤后8小时（56 ± 6和26±4 ml/分钟对比57 ± 6和40 ±4毫升/分钟；车辆和 BQ-123 治疗后动物受伤前和流体冲击损伤后 8 小时的脑血流量分别为 100 g）。液体冲击损伤导致顶叶皮质中神经元细胞损失和微管相关蛋白 2 免疫反应性降低，而 BQ-123 会减弱这些免疫反应性。这些数据表明，液体冲击损伤引起的脑血流动力学变化与神经元损伤相关，并且内皮素-1有助于液体冲击损伤引起的组织病理学变化。
This study characterized the association between endothelin-1, cerebral hemodynamics, and histopathology after fluid percussion brain injury in the newborn pig. Lateral fluid percussion injury was induced in newborn pigs equipped with a closed cranial window. Cerebral blood flow was determined with radiolabeled microspheres and cerebrospinal fluid endothelin-1 was measured by radioimmunoassay. Cerebrospinal fluid endothelin-1 was increased from 26 ± 4 to 296 ± 37 pg/ml (~10−10M) at 8 hours following fluid percussion injury. Post-injury treatment (30 minutes) with the endothelin-1 antagonist BQ-123 (1 mg/kg, intravenous) blocked pial artery vasoconstriction to topical endothelin-1 (~10−10M) and blunted fluid percussion injury-induced reductions in cerebral blood flow at 8 hours post-insult (56 ± 6 and 26±4 ml/minute versus 57 ± 6 and 40 ± 4 ml/minute; 100 g for cerebral blood flow before injury and 8 hours post-fluid percussion injury in vehicle and BQ-123 post-treated animals, respectively). Fluid percussion injury resulted in neuronal cell loss and decreased microtubule associated protein 2 immunoreactivity in the parietal cortex, which were blunted by BQ-123. These data indicate that fluid percussion injury-induced changes in cerebral hemodynamics are associated with neuronal damage and that endothelin-1 contributes to fluid percussion injury-induced histopathologic changes.