Bogdan I, Leib S L, Bergeron M, Chow L, Täuber M G
San Francisco General Hospital, Department of Neurology, San Francisco VA Medical Center, USA.
J Infect Dis. 1997 Sep;176(3):693-7. doi: 10.1086/514092.
To evaluate the role of tumor necrosis factor-alpha (TNF-alpha) in neuronal injury in experimental group B streptococcal meningitis, infected neonatal rats were treated with a monoclonal antibody against TNF-alpha (20 mg/kg intraperitoneally) or saline given at the time of infection. Histopathology after 24 h showed necrosis in the cortex and apoptosis in the hippocampal dentate gyrus. Treated animals had significantly less hippocampal injury than did controls (P < .001) but had similar cortical injury and cerebrospinal fluid (CSF) inflammation. The antibody was then administered directly intracisternally (170 microg) to test whether higher CSF concentrations reduced inflammation or cortical injury. Again, hippocampal apoptosis was significantly reduced (P < .01), while cortical injury and inflammation were not. Thus, TNF-alpha played a critical role in neuronal apoptosis in the hippocampus, while it was not essential for the development of inflammation and cortical injury in this model.
为评估肿瘤坏死因子-α（TNF-α）在实验性B族链球菌脑膜炎神经元损伤中的作用，给受感染的新生大鼠在感染时腹腔注射抗TNF-α单克隆抗体（20毫克/千克）或生理盐水进行治疗。24小时后的组织病理学检查显示，皮质有坏死，海马齿状回有凋亡。接受治疗的动物海马损伤明显少于对照组（P <.001），但皮质损伤和脑脊液（CSF）炎症与对照组相似。然后将抗体直接注入脑池（170微克），以测试更高的脑脊液浓度是否能减轻炎症或皮质损伤。同样，海马凋亡明显减少（P <.01），而皮质损伤和炎症则没有减轻。因此，TNF-α在海马神经元凋亡中起关键作用，而在该模型中，它对炎症和皮质损伤的发生并非必不可少。
