The role of excitatory amino acids in traumatic brain injury and effects of hypothermia

兴奋性氨基酸在创伤性脑损伤中的作用和低温的影响

• 批准号: 07671524
• 负责人: FUJISAWA Hirosuke
• 金额: $ 1.34万
• 依托单位: Yamaguchi Univeristy
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671524/
• 关键词: head injury; cerebral contusion; excitatory amino acids; glutamate; hypothermia; cerebral blood flow; microdialysis; hypoxia; 低血圧; 外傷性脳損傷; ラット

Purpose : The purpose of this study was to investigate the effects of hypothermia on the release of the excitatory amino acids (EAAs) and cerebral blood flow (CBF) during cerebral contusion. The effects of hypothermia on hypoxia-induced changes in the amino acids were also investigated.Methods : Adult male Wistar rats were used. The animals were devieded two experimental groups : normothermia group (37ﾟC) and hypothermia group (32ﾟC). Cerebral contusion was created in the parietal cortex by a weight-drop method. (1) CBF was monitored using the hydrogen clearance technique, and cortical levels of EAAs were measured by intracerebral microdialysis. (2) Cerebral hypoxia (PaO2 : 30-40 mmHg) was induced for 60 min. CBF was measured by laser-Doppler flowmetry, and the extracelular concentrations of EAAs were measured by microdialysis. (3) After cerebral contusion was created, hypoxia was induced. CBF and the EAA concentrations were measured by the same methods as (2).Results : (1) CBF in both … More groups decreased significantly after contusion but never fell below the threshold for ischemia. Cortical levels of EAAs were significantly increased after contusion in each group. However, these increases were greater in the hypothermic than in the normothermic rats. (2) Arterial blood pressurefell markedly during hypoxia in both groups, and returned to the normal range after cessation of hypoxia. CBF showed modest increases during hypoxia in both groups. Mild hypothermia abolished the EAA surge seen under norjmothermic conditions. (3) EAA levels were significantly increased after contusion in each group, and these increases were greater in the hypothermic than in the normothermic rats as the experiment (1). The EAA levels of the normothermic animals increased again after hypoxia induction. Mild hypothermia abolished such hypoxia-induced EAA surge.Conclusion : Hypothermic cerebroprotection in traumatic brain injury (TBI) is likely to occur through a kmechanism other than reduction in interstitial excitatory amino acids. It is postulated that the postsynaptic effects of hypothermia may be more important than the presynaptic effects, when CBF is kept above the ischemic threshold. Cerebral hypoxia contributes to the complex spectrum of pathology of TBI.The results of these study suggest that secondary damage caused by cerebral hypoxia can be ameliorated by hypothermia. Less

目的：本研究的目的是探讨低温对脑挫裂伤过程中兴奋性氨基酸（EAA）释放和脑血流量（CBF）的影响。还研究了低温对缺氧引起的氨基酸变化的影响。方法：使用成年雄性Wistar大鼠。将动物分为两个实验组：常温组（37℃）和低温组（32℃）。通过坠落法在顶叶皮层造成脑挫裂伤。 (1)使用氢清除技术监测CBF，并通过脑内微透析测量皮质EAA水平。 (2)诱导脑缺氧(PaO2：30-40mmHg)60分钟。通过激光多普勒血流计测量CBF，通过微透析测量EAA的细胞外浓度。 (3)脑挫裂伤后，引起缺氧。 CBF和EAA浓度的测量方法与（2）相同。结果：（1）挫伤后两组的CBF均显着下降，但从未降至缺血阈值以下。每组挫伤后皮层 EAA 水平均显着升高。然而，这些增加在低温大鼠中比在常温大鼠中更大。 (2)两组缺氧期间动脉血压均明显下降，缺氧停止后恢复至正常范围。两组的CBF在缺氧期间均表现出适度的增加。轻度低温消除了常温条件下出现的 EAA 激增。 (3)各组挫伤后EAA水平均显着升高，且与实验(1)一样，低温组大鼠的升高幅度大于常温组大鼠。常温动物缺氧诱导后EAA水平再次升高。轻度低温消除了这种缺氧引起的 EAA 激增。结论：创伤性脑损伤 (TBI) 中的低温脑保护作用可能是通过除间质兴奋性氨基酸减少之外的其他机制发生的。据推测，当 CBF 保持在缺血阈值以上时，低温的突触后效应可能比突触前效应更重要。脑缺氧导致了 TBI 的复杂病理学谱。这些研究结果表明，脑缺氧引起的继发性损伤可以通过低温得到改善。较少的

项目成果

藤澤 博亮 ら: "ラット外傷性脳損傷後の脳血流と細胞外液中アミノ酸に対する軽度低体温の影響" 神経外傷. 18. 14-18 (1995)

Hiroaki Fujisawa 等人：“轻度低温对大鼠创伤性脑损伤后脑血流和细胞外液中氨基酸的影响”《神经创伤》18. 14-18 (1995)。

Fujisawa H,koizumi H,Die X,Ito H,Maekawa T: "Effects of mild hypothermia on cerebral blood flow and extracellular levels of amino acids following traumatic brain injury in the rat." Neurotraumatology. 18. 14-18 (1995)

Fujisawa H、koizumi H、Die X、Ito H、Maekawa T：“轻度低温对大鼠脑外伤后脑血流和细胞外氨基酸水平的影响。”

Fujisawa H et al.: "Effects of mild hypothermia on nitric oxide synthesis following cerebral hypoxia in the rat." Advances in Neurotrauma Research. 8. 72-73 (1996)

Fujisawa H 等人：“轻度低温对大鼠脑缺氧后一氧化氮合成的影响。”