Meli Damian N, Christen Stephan, Leib Stephen L, Täuber Martin G
Institute for Infectious Diseases, University of Berne, Berne, Switzerland.
Curr Opin Infect Dis. 2002 Jun;15(3):253-7. doi: 10.1097/00001432-200206000-00007.
In spite of improved antimicrobial therapy, bacterial meningitis still results in brain damage leading to significant long-term neurological sequelae in a substantial number of survivors, as confirmed by several recent studies. Meningitis caused by Streptococcus pneumoniae is associated with a particularly severe outcome. Experimental studies over the past few years have increased our understanding of the molecular mechanisms underlying the events that ultimately lead to brain damage during meningitis. Necrotic damage to the cerebral cortex is at least partly mediated by ischemia and oxygen radicals and therefore offers a promising target for adjunctive therapeutic intervention. Neuronal apoptosis in the hippocampus may represent the major pathological process responsible for cognitive impairment and learning disabilities in survivors. However, the mechanisms involved in causing this damage remain largely unknown. Anti-inflammatory treatment with corticosteroids aggravates hippocampal damage, thus underlining the potential shortcomings of current adjuvant strategies. In contrast, the combined inhibition of matrix metalloproteinase and tumour necrosis factor-alpha converting enzyme protected both the cortex and hippocampus in experimental meningitis, and may represent a promising new approach to adjunctive therapy. It is the hope that a more refined molecular understanding of the pathogenesis of brain damage during bacterial meningitis will lead to new adjunctive therapies.
尽管抗菌治疗有所改进，但正如最近几项研究所证实的那样，细菌性脑膜炎仍会导致脑损伤，致使大量幸存者出现严重的长期神经后遗症。肺炎链球菌引起的脑膜炎与特别严重的后果相关。过去几年的实验研究增进了我们对脑膜炎期间最终导致脑损伤的事件背后分子机制的理解。大脑皮质的坏死性损伤至少部分由局部缺血和氧自由基介导，因此为辅助治疗干预提供了一个有前景的靶点。海马体中的神经元凋亡可能是导致幸存者认知障碍和学习障碍的主要病理过程。然而，造成这种损伤的机制在很大程度上仍不清楚。用皮质类固醇进行抗炎治疗会加重海马体损伤，从而凸显了当前辅助治疗策略的潜在缺陷。相比之下，在实验性脑膜炎中，联合抑制基质金属蛋白酶和肿瘤坏死因子-α转换酶可保护皮质和海马体，这可能代表了一种有前景的辅助治疗新方法。人们希望，对细菌性脑膜炎期间脑损伤发病机制有更精细的分子理解将带来新的辅助治疗方法。
