Wei Benjamin P C, Shepherd Robert K, Robins-Browne Roy M, Clark Graeme M, O'Leary Stephen J
Bionic Ear Institute, Department of Otolaryngology, University of Melbourne, Royal Victorian Eye & Ear Hospital, Melbourne, Victoria, Australia.
Otol Neurotol. 2006 Sep;27(6):844-54. doi: 10.1097/01.mao.0000231603.25961.f1.
The rat is a suitable animal to establish a model for the study of pneumococcal meningitis postcochlear implantation.
There has been an increase in the number of cases of cochlear implant-related meningitis. The most common organism identified was Streptococcus pneumoniae. Whether cochlear implantation increases the risk of pneumococcal meningitis in healthy subjects without other risk factors remains to be determined. Previous animal studies do not focus on the pathogenesis and risk of pneumococcal meningitis postimplantation and are based on relatively small animal numbers, making it difficult to assess the cause-and-effect relationship. There is, therefore, a need to develop a new animal model allowing direct examination of the pathogenesis of meningitis in the presence of a cochlear implant.
Eighteen nonimplanted rats were infected with 1 x 10 and 1 x 10 colony-forming units (CFU) of a clinical isolate of S. pneumoniae via three different inoculation routes (middle ear, inner ear, and i.p.) to examine for evidence of meningitis during 24 hours. Six implanted rats were infected with the highest amount of bacteria possible for each route of inoculation (4 x 10 CFU i.p., 3 x 10 CFU middle ear, and 1 x 10 CFU inner ear) to examine for evidence of meningitis with the presence of an implant. The histological pattern of cochlear infections for each of the three different inoculating routes were examined.
Pneumococcal meningitis was evident in all 6 implanted animals for each of the three different routes of inoculation. Once in the inner ear, bacteria were found to enter the central nervous system via either the cochlear aqueduct or canaliculi perforantes of the osseous spiral lamina, reaching the perineural and perivascular space then the internal acoustic meatus. The rate, extent, and pattern of infection within the cochleae depended on the route of inoculation. Finally, there was no evidence of pneumococcal meningitis observed in 18 nonimplanted rats inoculated at a lower concentration of S. pneumoniae when observed for 24 hours postinoculation.
Meningitis in implanted rats after inoculation with a clinical isolate of S. pneumoniae is possible via all three potential routes of infection via the upper respiratory tract. The lack of meningitis observed in the 18 nonimplanted rats suggests that longer postinoculation monitoring periods are required to ensure whether or not meningitis will develop. Based on this work, we have developed a new animal model that will allow quantitative risk assessment of meningitis postcochlear implantation, and the assessment of the efficacy of potential interventional strategies in future studies.
大鼠是建立用于研究人工耳蜗植入后肺炎球菌性脑膜炎模型的合适动物。
人工耳蜗相关脑膜炎的病例数有所增加。最常见的病原体是肺炎链球菌。在没有其他危险因素的健康受试者中，人工耳蜗植入是否会增加肺炎球菌性脑膜炎的风险仍有待确定。先前的动物研究未关注人工耳蜗植入后肺炎球菌性脑膜炎的发病机制和风险，且基于相对较少的动物数量，难以评估因果关系。因此，需要开发一种新的动物模型，以便在存在人工耳蜗的情况下直接检查脑膜炎的发病机制。
18只未植入人工耳蜗的大鼠通过三种不同接种途径（中耳、内耳和腹腔注射）分别感染1×10⁶和1×10⁷菌落形成单位（CFU）的肺炎链球菌临床分离株，以检查24小时内是否有脑膜炎迹象。6只已植入人工耳蜗的大鼠通过每种接种途径感染尽可能多的细菌（腹腔注射4×10⁶CFU、中耳3×10⁶CFU、内耳1×10⁶CFU），以检查在有植入物的情况下是否有脑膜炎迹象。检查三种不同接种途径各自的耳蜗感染组织学模式。
在三种不同接种途径的所有6只已植入人工耳蜗的动物中均明显出现肺炎球菌性脑膜炎。一旦进入内耳，细菌可通过蜗水管或骨螺旋板的穿孔小管进入中枢神经系统，到达神经周围和血管周围间隙，然后进入内耳道。耳蜗内感染的速率、范围和模式取决于接种途径。最后，在接种较低浓度肺炎链球菌的18只未植入人工耳蜗的大鼠接种后24小时观察期间，未发现肺炎球菌性脑膜炎的迹象。
接种肺炎链球菌临床分离株后，已植入人工耳蜗的大鼠可能通过上呼吸道的所有三种潜在感染途径发生脑膜炎。18只未植入人工耳蜗的大鼠未观察到脑膜炎，这表明需要更长的接种后监测期以确保是否会发生脑膜炎。基于这项工作，我们开发了一种新的动物模型，可用于人工耳蜗植入后脑膜炎的定量风险评估，以及在未来研究中评估潜在干预策略的疗效。
