Nau Roland, Brück Wolfgang
Dept of Neurology, University of Göttingen, University Hospital, Robert-Koch-Str. 40, D-37075, Göttingen, Germany.
Trends Neurosci. 2002 Jan;25(1):38-45. doi: 10.1016/s0166-2236(00)02024-5.
In bacterial meningitis, long-term neurological sequelae and death are caused jointly by several factors: (1) the systemic inflammatory response of the host, leading to leukocyte extravasation into the subarachnoid space, vasculitis, brain edema and secondary ischemia; (2) stimulation of resident microglia within the CNS by bacterial compounds; and (3) possible direct toxicity of bacterial compounds on neurons. Neuronal injury is mediated by the release of reactive oxygen intermediates, proteases, cytokines and excitatory amino acids, and is executed by the activation of transcription factors, caspases and other proteases. In experimental meningitis, dexamethasone as an adjunct to antibiotic treatment leads to an aggravation of neuronal damage in the hippocampal formation, suggesting that corticosteroids might not be the ideal adjunctive therapy. Several approaches that interfere selectively with the mechanisms of neuronal injury are effective in animal models, including the use of nonbacteriolytic protein synthesis-inhibiting antibiotics, antioxidants and inhibitors of transcription factors, matrix metalloproteinases, and caspases.
在细菌性脑膜炎中，长期神经后遗症和死亡是由多种因素共同导致的：（1）宿主的全身炎症反应，导致白细胞渗入蛛网膜下腔、血管炎、脑水肿和继发性缺血；（2）中枢神经系统内常驻小胶质细胞受到细菌化合物的刺激；以及（3）细菌化合物对神经元可能的直接毒性。神经元损伤由活性氧中间体、蛋白酶、细胞因子和兴奋性氨基酸的释放介导，并通过转录因子、半胱天冬酶和其他蛋白酶的激活来实现。在实验性脑膜炎中，地塞米松作为抗生素治疗的辅助药物会导致海马结构中神经元损伤加重，这表明皮质类固醇可能不是理想的辅助治疗药物。几种选择性干扰神经元损伤机制的方法在动物模型中有效，包括使用非溶菌性蛋白质合成抑制抗生素、抗氧化剂以及转录因子、基质金属蛋白酶和半胱天冬酶的抑制剂。
