Factors affecting excitatory amino acid release following severe human head injury
Factors affecting excitatory amino acid release following severe human head injury
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DOI：
10.3171/jns.1998.89.4.0507
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发表时间：
1998-10-01
影响因子：
4.1
通讯作者：
Young, HF
中科院分区：
文献类型：
--
作者：
Bullock, R;Zauner, A;Young, HF
最近的动物研究表明，兴奋性氨基酸（EAAs）在脑外伤和缺血后的神经元损伤中起主要作用。然而，EAA在严重脑损伤患者中的作用尚不清楚。细胞外间隙中过量的谷氨酸可能导致钠、钾和钙的不受控制的变化，破坏离子稳态，这可能导致严重的细胞肿胀和细胞死亡。作者评价了EEAs在人类创伤性脑损伤中的作用。在连续50例重型颅脑损伤患者中，将微透析探针与脑室引流导管或颅内压（ICP）监测仪一起沿着放置在灰质中，持续4天。使用高效液相色谱法分析EAA和结构氨基酸的水平。对氨基酸模式进行多因素分析，并检验其与临床参数和结局的相关性。在30%的患者中，EAA水平增加至正常值的50倍，并且在每个患者和整个组中与结构氨基酸水平显著相关（p < 0.01）。继发性缺血性脑损伤和局灶性挫伤与高EAA水平（27 +/- 22 μ mol/L）密切相关。持续高ICP和不良预后与高水平EAA（谷氨酸> 20 μ mol/L; p < 0.01）显著相关。EAA的释放与结构氨基酸的释放密切相关，因此可能反映了膜微孔的非特异性发育，而不是突触前神经元囊泡胞吐。局灶性挫伤和缺血事件患者中EAA释放的幅度可能足以加剧神经元损伤，这些患者可能是未来谷氨酸拮抗剂治疗的最佳候选人。
Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury.Methods. In SO consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27 +/- 22 mu mol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 mu mol/L; p < 0.01).Conclusions. The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.