Division of Neurosurgery, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.
Am J Pathol. 2013 Aug;183(2):450-8. doi: 10.1016/j.ajpath.2013.04.031. Epub 2013 Jun 7.
Decompressive craniectomy is often required after head trauma, stroke, or cranial bleeding to control subsequent brain swelling and prevent death. The infection rate after cranial bone flap replacement ranges from 0.8% to 15%, with an alarming frequency caused by methicillin-resistant Staphylococcus aureus, which is problematic because of recalcitrance to antibiotic therapy. Herein we report the establishment of a novel mouse model of S. aureus cranial bone flap infection that mimics several aspects of human disease. Bacteria colonized bone flaps for up to 4 months after infection, as revealed by scanning electron microscopy and quantitative culture, demonstrating the chronicity of the model. Analysis of a human cranial bone flap with confirmed S. aureus infection by scanning electron microscopy revealed similar structural attributes as the mouse model, demonstrating that it closely parallels structural facets of human disease. Inflammatory indices were most pronounced within the subcutaneous galeal compartment compared with the underlying brain parenchyma. Specifically, neutrophil influx and chemokine expression (CXCL2 and CCL5) were markedly elevated in the galea, which demonstrated substantial edema on magnetic resonance images, whereas the underlying brain parenchyma exhibited minimal involvement. Evaluation of immune mechanisms required for bacterial containment and inflammation revealed critical roles for MyD88-dependent signaling and neutrophils. This novel mouse model of cranial bone flap infection can be used to identify key immunologic and therapeutic mechanisms relevant to persistent bone flap infection in humans.
去骨瓣减压术常用于颅脑创伤、中风或颅脑出血后，以控制继发的脑肿胀并预防死亡。颅骨瓣置换术后的感染率为 0.8%至 15%，其中由耐甲氧西林金黄色葡萄球菌引起的感染率令人震惊，因为其对抗生素治疗具有顽固性。在此，我们报告了一种新的耐甲氧西林金黄色葡萄球菌颅骨骨瓣感染的小鼠模型的建立，该模型模拟了人类疾病的多个方面。扫描电子显微镜和定量培养显示，感染后细菌在颅骨瓣上定植长达 4 个月，表明该模型具有慢性特征。通过扫描电子显微镜对确诊为耐甲氧西林金黄色葡萄球菌感染的人类颅骨骨瓣进行分析，发现与小鼠模型具有相似的结构特征，表明其与人类疾病的结构方面非常相似。与脑实质相比，皮下帽状腱膜间隙的炎症指数最为明显。具体而言，中性粒细胞浸润和趋化因子表达（CXCL2 和 CCL5）在帽状腱膜中显著升高，磁共振成像显示明显水肿，而脑实质下方则很少受累。评估细菌控制和炎症所需的免疫机制表明，MyD88 依赖性信号和中性粒细胞起着关键作用。这种新的颅骨骨瓣感染小鼠模型可用于确定与人类颅骨骨瓣持续感染相关的关键免疫和治疗机制。
