Role of tumor necrosis factor-α in sensorineural hearing loss after bacterial meningitis
Role of tumor necrosis factor-α in sensorineural hearing loss after bacterial meningitis
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DOI：
10.1097/01.mao.0000178121.28365.0d
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发表时间：
2005-07-01
影响因子：
2.1
通讯作者：
Brodie, HA
中科院分区：
文献类型：
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作者：
Aminpour, S;Tinling, SP;Brodie, HA
假设：用肿瘤坏死因子-α 抗体阻断肿瘤坏死因子-α 将减少与肺炎链球菌脑膜炎相关的耳蜗损伤和听力损失的程度。背景：炎症介质在与细菌性脑膜炎相关的发病中发挥重要作用，包括听力损失和骨化性迷路炎。先前的研究表明，非特异性阻断此类通路可减轻听力损失。方法：将 50 只蒙古沙鼠分为四组。进行听觉脑干反应测试来测量听力阈值。第I组和第2组诱导肺炎链球菌脑膜炎。然后第2组腹腔内单次注射肿瘤坏死因子-α抗体，而第I组接受磷酸盐缓冲盐水。第 3 组和第 4 组中未感染的动物植入渗透泵，连续 8 天鞘内输送肿瘤坏死因子-α（第 4 组）或磷酸盐缓冲盐水（第 3 组）。 6周后，重复听觉脑干反应测试。收获耳蜗并进行组织形态计量学分析。结果：也接受肿瘤坏死因子-α抗体的患有肺炎链球菌脑膜炎的第2组动物的听力损失比仅患有脑膜炎的第1组动物显着减少。 4、8、16 和 32 kHz 处的平均阈值降低分别为 31、30、25 和 28 dB 声压级（每个均 p < 0.0092）。此外，组织形态计量学分析显示，第 2 组对柯蒂氏器、螺旋神经节、螺旋韧带和血管纹的损伤显着减少。相反，与磷酸盐缓冲盐水对照组（第 4 组）相比，肿瘤坏死因子-α 诱导的脑膜炎动物（第 3 组）听力损失增加，所有频率下 p < 0.0001。结论：肿瘤坏死 α因子在细菌性脑膜炎后的耳蜗损伤中发挥重要作用。阻断肿瘤坏死因子-α 可减少脑膜炎后听力损失和耳蜗损伤。与细菌性脑膜炎类似，鞘内肿瘤坏死因子-α诱导脑膜炎也会导致听力丧失和耳蜗损伤。
Hypothesis: Blockade of tumor necrosis factor-alpha with tumor necrosis factor-alpha antibody will reduce the extent of cochlear injury and hearing loss associated with Streptococcus pneumoniae meningitis.Background: Inflammatory mediators play a significant role in the morbidity associated with bacterial meningitis, including hearing loss and labyrinthitis ossificans. Previous studies have shown the attenuation of hearing loss by the nonspecific blockade of such pathways.Methods: Fifty Mongolian gerbils were divided into four groups. Auditory brainstem response testing was conducted to measure hearing thresholds. Streptococcus pneumoniae meningitis was induced in Groups I and 2. Group 2 was then given a single intraperitoneal injection of tumor necrosis factor-alpha antibody, whereas Group I received phosphate-buffered saline. Uninfected animals in Groups 3 and 4 were implanted with osmotic pumps that delivered a continuous 8-day intrathecal flow of either tumor necrosis factor-alpha (Group 4) or phosphate-buffered saline (Group 3). After 6 weeks, auditory brainstem response testing was repeated. The cochleas were harvested and analyzed histomorphometrically.Results: Group 2 animals with Streptococcus pneumoniae meningitis that also received tumor necrosis factor-alpha antibody developed significantly less hearing loss than Group I animals with meningitis alone. The decrease in the average threshold at 4, 8, 16, and 32 kHz was 31, 30, 25, and 28 dB sound pressure level, respectively (p < 0.0092 for each). Furthermore, histomorphometric analysis showed significantly less damage to the organ of Corti, spiral ganglion, spiral ligament, and stria vascularis in Group 2. Conversely, tumor necrosis factor-alpha induced meningitis animals (Group 3) showed increased hearing loss compared with phosphate-buffered saline controls (Group 4), with p < 0.0001 at all frequencies.Conclusion: Tumor necrosis factor-alpha plays an important role in cochlear injury after bacterial meningitis. Blockade of tumor necrosis factor-alpha reduces postmeningitic hearing loss and cochlear injury. Induction of meningitis with intrathecal tumor necrosis factor-alpha also resulted in hearing loss and cochlear injury similar to bacterial meningitis.