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中华神经创伤外科电子杂志

中华神经创伤外科电子杂志 ›› 2019, Vol. 05 ›› Issue (02) : 101 -105. doi: 10.3877/cma.j.issn.2095-9141.2019.02.009

所属专题： 文献；

基础研究

局灶性脑低温处理对大鼠创伤性脑损伤模型的保护作用
费晓炜1, 徐如祥1, 魏明海2, 贺业霆2,†()   
  1. 1. 100700　北京，解放军总医院第七医学中心原附属八一脑科医院
    2. 116023　大连，大连医科大学附属第二医院神经外科
  • 收稿日期:2019-02-19 出版日期:2019-04-15
  • 通信作者: 贺业霆
  • 基金资助:
    辽宁省自然科学基金(20170540277)

Protective effect of focal cerebral hypothermia on traumatic brain injury model

Xiaowei Fei1, Ruxiang Xu1, Minghai Wei2, Yeting He2,†()   

  1. 1. Affiliated BaYi Brain Hospital, The 7th Medical Center of the Chinese People’s Liberation Army General Hospital, Beijing 100700, China
    2. Department of Neurosurgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China
  • Received:2019-02-19 Published:2019-04-15
  • Corresponding author: Yeting He
  • About author:
    Correspondence author: He Yeting, Email:
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引用本文：

费晓炜, 徐如祥, 魏明海, 贺业霆. 局灶性脑低温处理对大鼠创伤性脑损伤模型的保护作用[J]. 中华神经创伤外科电子杂志, 2019, 05(02): 101-105.

Xiaowei Fei, Ruxiang Xu, Minghai Wei, Yeting He. Protective effect of focal cerebral hypothermia on traumatic brain injury model[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2019, 05(02): 101-105.

目的

探讨局灶性低温处理对SD大鼠创伤性脑损伤（TBI）模型的保护作用并探讨其相关机制。

方法

将15只雄性SD大鼠随机平均分成假手术组（sham），非冷却组（non-cooling）和冷却组（cooling）。Non-cooling组和cooling组制作TBI模型，3组实验同步进行，创伤后低温处理3 h，复温3 h，过程中检测大鼠血气、皮层脑电。复温结束处死大鼠后，对脑组织进行TTC和HE染色以评价脑死亡和脑水肿情况，Western blot检测相关机制蛋白表达情况。

结果

Sham组和non-cooling组受外部刺激脑组织代谢升高，cooling组较其他组脑组织代谢低，TTC和HE染色显示cooling组脑死亡的面积和细胞死亡数量均少于non-cooling组，差异均具有统计学意义（P<0.05）。大鼠TBI后局灶性低温处理能显著降低大脑皮层的癫痫样棘波，在回温时这种不完全抑制持续存在，且低温处理降低了GABAB1R蛋白的表达，差异均具有统计学意义（P<0.05）。Cooling组的脑水肿情况较non-cooling组轻，且cooling组AQP4蛋白表达降低，差异均具有统计学意义（P<0.05）。

结论

局灶性低温处理对TBI大鼠具有保护作用，能显著减轻TBI引起的脑水肿，抑制大脑皮层的癫痫样棘波，具体机制可能分别与GABAB1R和AQP4相关。为临床治疗TBI提供了一种更加安全、简单有效的方法。

关键词: 创伤性脑损伤, 亚低温治疗, 癫痫样棘波, 水肿
Objective

To explore the protective effect of focal cerebral hypothermia on traumatic brain injury (TBI) model in SD rats and the underlying mechanisms.

Methods

Fifteen male SD rats were randomly divided into a sham group, a non-cooling group, and a cooling group, with 5 in each group. The TBI model was made by non-cooling group and cooling group. Three groups of experiments were performed simultaneously. After trauma, the mice were treated with hypothermia for 3 h and rewarmed for 3 h. Rat blood gas and cortical brain electricity were detected during the experiment. Rats were sacrificed at the end of rewarming, and brain tissue was stained with TTC or HE to evaluate brain death. The cerebral edema was evaluated and the expression of related proteins was detected by Western blot.

Results

Sham group and non-cooling group were increased in metabolism by externally stimulated brain tissue, and metabolism of cooling group is low (P<0.05). TTC and HE staining showed that the area of brain death and cell death in the cooling group were less than those in the non-cooling group (P<0.05). Focal hypothermia after TBI significantly reduces epileptic spikes in the cerebral cortex (P<0.05). This incomplete inhibition persists during rewarming, and hypothermia treatment reduces the expression of GABAB1R (P<0.05). Brain edema in the cooling group was significantly improved compared with the non-cooling group (P<0.05) and expression of AQP4 protein in the cooling group was significantly lower (P<0.05).

Conclusion

Focal hypothermia has a protective effect on TBI rats, which significantly reduce brain edema caused by TBI and inhibit epileptic spikes in the cerebral cortex. The underlying mechanism may be related to GABAB1R and AQP4, respectively. It provides a safer, simpler and more effective method for clinical treatment of TBI.

Key words: Traumatic brain injury, Focal cerebral hypothermia, Epileptic spike, Edema
图1 手术操作示意图
图2 实验全程大鼠血气记录
图3 大鼠脑组织TTC染色和HE染色
图5 创伤性脑损伤后cooling组和non-cooling组水肿情况及AQP4表达变化
[1]
Clifton GL, Allen S, Barrodale P, et al. A phase II study of moderate hypothermia in severe brain injury[J]. J Neurotrauma, 1993, 10(3): 263-271, discussion 273.
[2]
Marion DW, Obrist WD, Earlier PM, et al. The use of moderate therapeutic hypothermia for patients with severe head injuries: a preliminary report[J]. J Neurosurg, 1993, 79(3): 354-362.
[3]
Oku T, Fujii M, Tanaka N, et al. The influence of focal brain cooling on neurophysiopathology: validation for clinical application[J]. J Neurosurg, 2009, 110(6): 1209-1217.
[4]
Clark DL, Penner M, Wowk S, et al. Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat[J]. Exp Neurol, 2009, 220(2): 391-399.
[5]
Sun H, Zheng M, Wang Y, et al. Brain tissue partial pressure of oxygen predicts the outcome of severe traumatic brain injury under mild hypothermia treatment[J]. Neuropsychiatr Dis Treat, 2016, 12: 2125-2129.
[6]
Dong HJ, Zhao ML, Li XH, et al. Hypothermia-modulating matrix elasticity of injured brain promoted neural lineage specification of mesenchymal stem cells[J]. Neuroscience, 2018, 377: 1-11.
[7]
Zhang FC, Dong HP, Lv T, et al. Moderate hypothermia inhibits microglial activation after traumatic brain injury by modulating autophagy/apoptosis and the MyD88-dependent TLR4 signaling pathway[J]. J Neuroinflammation, 2018, 15(1): 273.
[8]
Liu B, Wang L, Cao Y, et al. Hypothermia pretreatment improves cognitive impairment via enhancing synaptic plasticity in a traumatic brain injury model[J]. Brain Res, 2017, 1672: 18-28.
[9]
Jin Y, Lin Y, Feng JF, et al. Moderate hypothermia significantly decreases hippocampal cell death involving autophagy pathway after moderate traumatic brain injury[J]. J Neurotrauma, 2015, 32(14): 1090-1100.
[10]
Mattison KA, Butler KM, Inglis GAS, et al. SLC6A1 variants identified in epilepsy patients reduce γ-aminobutyric acid transport[J]. Epilepsia, 2018, 59: e135-e141.
[11]
Princivalle AP, Duncan JS, Thom M, et al. GABA(B1a), GABA(B1b) and GABA(B2) mRNA variants expression in hippocampus resected from patients with temporal lobe epilepsy[J]. Neuroscience, 2003, 122(4): 975-984.
[12]
Saadoun S, Papadopoulos MC. Aquaporin-4 in brain and spinal cord oedema[J]. Neuroscience, 2010, 168(4): 1036-1046.
[13]
Tait MJ, Saadoun S, Bell BA, et al. Increased brain edema in aqp4-null mice in an experimental model of subarachnoid hemorrhage[J]. Neuroscience, 2010, 167(1): 60-67.
[14]
Tang Y, Wu P, Su J, et al. Effects of aquaporin-4 on edema formation following intracerebral hemorrhage[J]. Exp Neurol, 2010, 223(2): 485-495.
[15]
Kapoor S, Kim SM, Farook JM, et al. Foxo3a transcriptionally upregulates AQP4 and induces cerebral edema following traumatic brain injury[J]. J Neurosci, 2013, 33(44): 17398-17403.
[16]
Marmarou CR, Liang X, Abidi NH, et al. Selective vasopressin-1a receptor antagonist prevents brain edema, reduces astrocytic cell swelling and GFAP, V1aR and AQP4 expression after focal traumatic brain injury[J]. Brain Res, 2014, 1581(10): 89-102.
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