Hemorrhagic Shock after Experimental Traumatic Brain Injury in Mice: Effect on Neuronal Death
Hemorrhagic Shock after Experimental Traumatic Brain Injury in Mice: Effect on Neuronal Death
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DOI：
10.1089/neu.2008.0512
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发表时间：
2009-06-01
影响因子：
4.2
通讯作者：
Kochanek, Patrick M.
中科院分区：
文献类型：
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作者：
Dennis, Alia Marie;Haselkorn, M. Lee;Kochanek, Patrick M.
恐怖袭击受害者中，爆炸伤引起的脑外伤 (TBI) 通常会并发失血性休克 (HS)。大多数实验性 TBI 后 HS 的研究都集中在颅内压上。很少有人探讨 HS 对 TBI 后神经元死亡的影响，而且还没有在小鼠身上进行过研究。我们假设实验性 TBI 后 HS 会加剧 CA1 海马神经元死亡。 C57BL6J 雄性小鼠用异氟烷麻醉，监测平均动脉血压 (MAP)，并将受控皮质冲击 (CCI) 传递至左侧顶叶皮质，然后持续麻醉（仅 CCI），或 60 或 90 分钟的容量控制 HS。还研究了平行 60 分钟或 90 分钟仅 HS 组。 HS (+/-CCI) 后，在 30 分钟的院前复苏阶段，使用 6% 羟乙基淀粉，目标 MAP >= 50 mm Hg。然后，重新输注流下的血液，并在 30 分钟的最终护理阶段给予羟乙基淀粉，目标 MAP >= 60 mm Hg。在24小时（氟玉C）或7天（CA1和CA3海马神经元计数）时评估神经损伤。 HS 将所有组中的 MAP 降低至 30-40 mm Hg，与仅 CCI 组相比，p < 0.05。 90 分钟 CCI + HS 组的同侧 CA1 神经元计数减少为 16.5 +/- 14.1，而仅 CCI、60 分钟 HS、90 分钟组中的同侧 CA1 神经元计数减少为 30.8 +/- 6.8、32.3 +/- 7.6、30.6 +/- 2.2、28.1 +/- 2.2 神经元/100 μm仅 HS 和 60 分钟 CCI + HS 分别全部 p < 0.05。 CA3 神经元计数在各组之间没有差异。 Fluorojade C 染色证实 90 分钟 CCI + HS 组 CA1 区神经变性。我们的数据表明，CCI 后 HS 导致的神经元死亡加剧存在一个关键时间窗口，并且可能对在严峻环境中导致最终治疗延迟的爆炸伤受害者产生影响。
Traumatic brain injury (TBI) from blast injury is often complicated by hemorrhagic shock (HS) in victims of terrorist attacks. Most studies of HS after experimental TBI have focused on intracranial pressure; few have explored the effect of HS on neuronal death after TBI, and none have been done in mice. We hypothesized that neuronal death in CA1 hippocampus would be exacerbated by HS after experimental TBI. C57BL6J male mice were anesthetized with isoflurane, mean arterial blood pressure (MAP) was monitored, and controlled cortical impact (CCI) delivered to the left parietal cortex followed by continued anesthesia (CCI-only), or either 60 or 90 min of volume-controlled HS. Parallel 60- or 90-min HS-only groups were also studied. After HS (+/-CCI), 6% hetastarch was used targeting MAP of >= 50 mm Hg during a 30-min Pre-Hospital resuscitation phase. Then, shed blood was re-infused, and hetastarch was given targeting MAP of >= 60 mm Hg during a 30-min Definitive Care phase. Neurological injury was evaluated at 24 h (fluorojade C) or 7 days (CA1 and CA3 hippocampal neuron counts). HS reduced MAP to 30-40 mm Hg in all groups, p < 0.05 versus CCI-only. Ipsilateral CA1 neuron counts in the 90-min CCI + HS group were reduced at 16.5 +/- 14.1 versus 30.8 +/- 6.8, 32.3 +/- 7.6, 30.6 +/- 2.2, 28.1 +/- 2.2 neurons/100 mu m in CCI-only, 60-min HS-only, 90-min HS-only, and 60-min CCI + HS, respectively, all p < 0.05. CA3 neuron counts did not differ between groups. Fluorojade C staining confirmed neurodegeneration in CA1 in the 90-min CCI + HS group. Our data suggest a critical time window for exacerbation of neuronal death by HS after CCI and may have implications for blast injury victims in austere environments where definitive management is delayed.