The long-term microvascular and behavioral consequences of experimental traumatic brain injury after hypothermic intervention.
The long-term microvascular and behavioral consequences of experimental traumatic brain injury after hypothermic intervention.
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低温干预后实验性脑外伤的长期微血管和行为后果。
DOI：
10.1089/neu.2008.0797
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发表时间：
2009
影响因子：
4.2
通讯作者：
Povlishock,JohnT
中科院分区：
文献类型：
--
作者：
Wei,EnochP;Hamm,RobertJ;Baranova,AnnaI;Povlishock,JohnT
创伤性脑损伤(TBI)可引起脑血管功能障碍，反映在对多种血管扩张剂反应的改变上。虽然以前的报道主要集中在短期的血管变化上，但很少有人研究这些血管变化超过7天，或者试图将这些变化与任何持续的行为变化或潜在的治疗调节联系起来。因此，我们评估了实验性脑外伤对微血管和行为的长期影响，以及通过低温对其治疗的调节。在本研究中，一组损伤后不处理，另一组损伤后1 h后进行120 分钟的低温治疗，然后缓慢复温，第三组为非损伤组。在颅脑损伤后1周或3周，用不同的血管扩张剂，包括乙酰胆碱、高碳酸血症、腺苷、匹那地尔和硝普钠，对装备有软脑膜微血管可视化的颅窗的动物进行挑战。此外，所有动物在伤后1周进行前庭运动测试，存活3周的动物在Morris水迷宫(MWM)中进行测试。这项研究的结果表明，颅脑损伤导致了长期的血管功能障碍，改变了血管对各种血管扩张剂的反应性，这种情况在延迟120分钟的低温治疗后得到显著改善。相比之下，来自MWM任务的数据表明，受伤的动物在空间记忆测试中表现出持续的缺陷，低温没有起到保护作用。总之，这些数据表明，脑外伤可以引起长期存在的脑血管和空间记忆功能障碍，这些功能障碍对低温干预表现出不同的反应。这些发现进一步说明了创伤性脑损伤的复杂性，并强调了所选择的低温干预不一定会产生全球保护性反应。
Traumatic brain injury (TBI) has been demonstrated to induce cerebral vascular dysfunction that is reflected in altered responses to various vasodilators. While previous reports have focused primarily on the short-term vascular alterations, few have examined these vascular changes for more than 7 days, or have attempted to correlate these alterations with any persisting behavioral changes or potential therapeutic modulation. Accordingly, we evaluated the long-term microvascular and behavioral consequences of experimental TBI and their therapeutic modulation via hypothermia. In this study, one group was injured with no treatment, another group was injured and 1 h later was treated with 120 min of hypothermia followed by slow rewarming, and a third group was non-injured. Animals equipped with cranial windows for visualization of the pial microvasculature were challenged with various vasodilators, including acetylcholine, hypercapnia, adenosine, pinacidil, and sodium nitroprusside, at either 1 or 3 weeks post-TBI. In addition, all animals were tested for vestibulomotor tasks at 1 week post-TBI, and animals surviving for 3 weeks post-TBI were tested in a Morris water maze (MWM). The results of this investigation demonstrated that TBI resulted in long-term vascular dysfunction in terms of altered vascular reactivity to various vasodilators, which was significantly improved with the use of a delayed 120-min hypothermic treatment. In contrast, data from the MWM task indicated that injured animals revealed persistent deficits in the spatial memory test performance, with hypothermia exerting no protective effects. Collectively, these data illustrate that TBI can evoke long-standing brain vascular and spatial memory dysfunction that manifest different responses to hypothermic intervention. These findings further illustrate the complexity of TBI and highlight the fact that the chosen hypothermic intervention may not necessarily exert a global protective response.