Post-Traumatic Hypoxia Exacerbates Neuronal Cell Death in the Hippocampus
Post-Traumatic Hypoxia Exacerbates Neuronal Cell Death in the Hippocampus
复制标题
DOI：
10.1089/neu.2011.1867
复制
发表时间：
2012-04-01
影响因子：
4.2
通讯作者：
Lyeth, Bruce G.
中科院分区：
文献类型：
--
作者：
Feng, Jun-feng;Zhao, Xueren;Lyeth, Bruce G.
缺氧经常发生在创伤性脑损伤（TBI）患者中，并与发病率和死亡率增加有关。本研究探讨了创伤后立即或延迟缺氧（吸入氧分数[FiO(2)] 11%）对大鼠中度液体冲击损伤后海马区急性神经元变性和长期神经元存活的影响。在实验1中，单独或在脑外伤后立即诱导缺氧15或30分钟。在实验2和实验3中，在脑外伤后立即或延迟至脑外伤后60分钟诱导缺氧30分钟。实验1采用荧光玉染色和体视学定量法对损伤后24 h海马区急性神经变性进行评价。在单独缺氧或合并TBI时，平均动脉血压显著降低约30%，随后在恢复到损伤前的FiO后迅速恢复到正常值(2)。在损伤后24小时测量时，单独缺氧未引起海马神经元变性。单独脑外伤导致各同侧海马区神经元变性，主要发生在CA2-CA3和齿状回。与单纯创伤性脑损伤相比，创伤性脑损伤加立即缺氧15或30分钟显著增加了大部分同侧海马区、对侧海门和齿状回的神经元损失。在实验2中，TBI加缺氧延迟30分钟，仅在同侧CA2-CA3中显著增加变性。在实验3中，30分钟的即时缺氧显著减少了脑损伤后14天CA3中存活的神经元数量。创伤后立即缺氧30分钟大大增加了所有海马区的易感性，为TBI合并缺氧/低血压提供了相关模型。这些数据强调了继发性损伤的重要性，更好地描述TBI患者所经历的损伤范围的必要性，以及在TBI患者的早期治疗中严格避免缺氧的重要性。
Hypoxia frequently occurs in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. This study examined the effects of immediate or delayed post-traumatic hypoxia (fraction of inspired oxygen [FiO(2)] 11%) on acute neuronal degeneration and long-term neuronal survival in hippocampal fields after moderate fluid percussion injury in rats. In Experiment 1, hypoxia was induced for 15 or 30 min alone or immediately following TBI. In Experiments 2 and 3, 30 min of hypoxia was induced immediately after TBI or delayed until 60 min after TBI. In Experiment 1, acute neurodegeneration was evaluated in the hippocampal fields 24 h after insults using Fluoro-Jade staining and stereological quantification. During hypoxia alone, or in combination with TBI, mean arterial blood pressure was significantly reduced by approximately 30%, followed by a rapid return to normal values upon return to pre-injury FiO(2). Hypoxia alone failed to cause hippocampal neuronal degeneration when measured at 24 h after insult. TBI alone resulted in neuronal degeneration in each ipsilateral hippocampal field, predominantly in CA2-CA3 and the dentate gyrus. Compared to TBI alone, TBI plus immediate hypoxia for either 15 or 30 min significantly increased neuronal loss in most ipsilateral hippocampal fields and in the contralateral hilus and dentate gyrus. In Experiment 2, TBI plus hypoxia delayed 30 min significantly increased degeneration only in ipsilateral CA2-CA3. In Experiment 3, 30 min of immediate hypoxia significantly reduced the numbers of surviving neurons in the CA3 at 14 days after TBI. The greatly increased vulnerability in all hippocampal fields by immediate 30 min post-traumatic hypoxia provides a relevant model of TBI complicated with hypoxia/hypotension. These data underscore the significance of the secondary insult, the necessity to better characterize the range of injuries experienced by the TBI patient, and the importance of strictly avoiding hypoxia in the early management of TBI patients.