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一种由单核细胞增生李斯特菌引起的菱形脑炎沙鼠模型。

A gerbil model for rhombencephalitis due to Listeria monocytogenes.

作者信息

Blanot S, Joly M M, Vilde F, Jaubert F, Clement O, Frija G, Berche P

机构信息

INSERM U411, Faculté de Médecine Necker-Enfants Malades, Paris, France.

出版信息

Microb Pathog. 1997 Jul;23(1):39-48. doi: 10.1006/mpat.1997.0131.

DOI:10.1006/mpat.1997.0131
PMID:9250779
Abstract

Rhombencephalitis due to Listeria monocytogenes is a frequent complication of human listeriosis, inducing a high mortality and severe neurological sequelae despite antibiotic therapy. However, there is no animal model which consistently reproduces clinical rhombencephalitis. Here, we present a model of Listeria rhombencephalitis in gerbils. Animals were inoculated in the middle ears with a low infective dose of L. monocytogenes, thus creating prolonged otitis media with persistent bacteremia. Gerbils developed a severe rhombencephalitis with circling syndrome, paresia, ataxia, rolling movements. The invasion of the central nervous system was visualized on living animals by resonance magnetic imaging and characterized by bacterial growth in the brain, reaching about 10(7) bacteria in the rhombencephalum by day 12 of infection. The histological lesions were mainly located in the brainstem, and consisted in coalescent, necrotic abscesses with perivascular sheaths, mimicking those observed in human rhombencephalitis. Bacteria were detected by electronmicroscopy inside infectious foci, either free in necrotic material or inside inflammatory cells, mainly polymorphonuclear cells. This gerbil model of Listeria rhombencephalitis will be useful to study the molecular mechanisms allowing bacteria to cross the blood-brain barrier, and to evaluate the intracerebral efficacy of antibiotics.

摘要

由单核细胞增生李斯特菌引起的菱形脑炎是人类李斯特菌病的常见并发症,尽管进行了抗生素治疗,但仍会导致高死亡率和严重的神经后遗症。然而,目前尚无能够始终如一地再现临床菱形脑炎的动物模型。在此,我们展示了一种沙鼠李斯特菌菱形脑炎模型。给动物中耳接种低感染剂量的单核细胞增生李斯特菌,从而导致持续性菌血症伴发长期中耳炎。沙鼠出现了严重的菱形脑炎,伴有转圈综合征、轻瘫、共济失调和翻滚运动。通过磁共振成像在活体动物上观察到中枢神经系统的侵袭,其特征是大脑中细菌生长,感染第12天时菱形脑内细菌数量达到约10⁷个。组织学病变主要位于脑干,表现为融合性坏死性脓肿伴血管周围鞘,类似于人类菱形脑炎中观察到的病变。通过电子显微镜在感染灶内检测到细菌,细菌要么游离于坏死物质中,要么存在于炎症细胞内,主要是多形核细胞。这种沙鼠李斯特菌菱形脑炎模型将有助于研究细菌穿越血脑屏障的分子机制,并评估抗生素的脑内疗效。

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