Department of Anesthesia and Critical Care Medicine, University of Milano, Neurosurgical Intensive Care Unit, Fondazione IRCCS Ca' Granda-Ospedale Maggiore Policlinico, Milano, Italy.
J Cereb Blood Flow Metab. 2011 Sep;31(9):1919-29. doi: 10.1038/jcbfm.2011.42. Epub 2011 Apr 6.
We investigated the occurrence of endotoxin (lipopolysaccharide, LPS) preconditioning in traumatic brain injury (TBI), evaluating the time window of LPS-induced protection, its persistence, and the associated molecular mechanisms. Mice received 0.1 mg/kg LPS or saline intraperitoneally and subsequently TBI (by controlled cortical impact brain injury) at various time intervals. Mice receiving LPS 3, 5, or 7 days before TBI showed attenuated motor deficits at 1 week after injury compared with mice receiving saline. Those receiving LPS 5 days before injury had also a reduced contusion volume (7.9±1.3 versus 12±2.3 mm(3)) and decreased cell death. One month after injury, the protective effect of LPS on contusion volume (14.5±1.2 versus 18.2±1.2 mm(3)) and neurologic function was still present. Traumatic brain injury increased glial fibrillary acidic protein, CD11b, CD68, tumor necrosis factor-α, interleukin (IL)-10, and IL-6 mRNA expression 24 hours after injury. Lipopolysaccharide administered 5 (but not 9) days before injury increased the expression of CD11b (233%) and of interferon β (500%) in uninjured mice, while it reduced the expression of CD68 (by 46%) and increased that of IL-6 (by 52%) in injured mice. Lipopolysaccharide preconditioning conferred a long-lasting neuroprotection after TBI, which was associated with a modulation of microglia/macrophages activity and cytokine production.
我们研究了内毒素（脂多糖，LPS）预处理在创伤性脑损伤（TBI）中的发生情况，评估了 LPS 诱导保护的时间窗口、其持久性以及相关的分子机制。小鼠接受 0.1mg/kg LPS 或生理盐水腹膜内注射，随后在不同时间间隔接受 TBI（通过皮质撞击脑损伤）。与接受生理盐水的小鼠相比，在 TBI 前 3、5 或 7 天接受 LPS 的小鼠在损伤后 1 周时运动缺陷减轻。在损伤前 5 天接受 LPS 的小鼠也具有较小的挫伤体积（7.9±1.3 与 12±2.3mm(3)）和减少的细胞死亡。损伤后 1 个月，LPS 对挫伤体积（14.5±1.2 与 18.2±1.2mm(3)）和神经功能的保护作用仍然存在。创伤性脑损伤后 24 小时增加了胶质纤维酸性蛋白、CD11b、CD68、肿瘤坏死因子-α、白细胞介素（IL）-10 和 IL-6mRNA 的表达。LPS 在损伤前 5 天（但不是 9 天）给药可增加未损伤小鼠中 CD11b（233%）和干扰素-β（500%）的表达，同时减少损伤小鼠中 CD68（46%）的表达并增加 IL-6（52%）的表达。LPS 预处理在 TBI 后提供了持久的神经保护作用，这与小胶质细胞/巨噬细胞活性和细胞因子产生的调节有关。
