Inserm U1148, Laboratory for Vascular Translational Science (LVTS), Bichat Hospital, Paris University, Sorbonne Paris Cité, Paris, France.
Department of Neurology, Saint-Antoine Hospital, AH-HP, Paris University, Sorbonne Universités, Paris, France.
Crit Care Med. 2019 Aug;47(8):e685-e692. doi: 10.1097/CCM.0000000000003796.
Embolic events from vegetations are commonly accepted as the main mechanism involved in neurologic complications of infective endocarditis. The pathophysiology may imply other phenomena, including vasculitis. We aimed to define the cerebral lesion spectrum in an infective endocarditis rat model.
Experimental model of Staphylococcus aureus or Enterococcus faecalis infective endocarditis. Neurologic lesions observed in the infective endocarditis model were compared with three other conditions, namely bacteremia, nonbacterial thrombotic endocarditis, and healthy controls.
Research laboratory of a university hospital.
Male Wistar rats.
Brain MRI, neuropathology, immunohistochemistry for astrocyte and microglia, and bacterial studies on brain tissue were used to characterize neurologic lesions.
In the infective endocarditis group, MRI revealed at least one cerebral lesion in 12 of 23 rats (52%), including brain infarctions (n = 9/23, 39%) and cerebral microbleeds (n = 8/23, 35%). In the infective endocarditis group, neuropathology revealed brain infarctions (n = 12/23, 52%), microhemorrhages (n = 10/23, 44%), and inflammatory processes (i.e., cell infiltrates including abscesses, vasculitis, meningoencephalitis, and/or ependymitis; n = 11/23, 48%). In the bacteremia group, MRI studies were normal and neuropathology revealed only hemorrhages (n = 2/11, 18%). Neuropathologic patterns observed in the nonbacterial thrombotic endocarditis group were similar to those observed in the infective endocarditis group. Immunochemistry revealed higher microglial activation in the infective endocarditis group (n = 11/23, 48%), when compared with the bacteremia (n = 1/11, 9%; p = 0.03) and nonbacterial thrombotic endocarditis groups (n = 0/7, 0%; p = 0.02).
This original model of infective endocarditis recapitulates the neurologic lesion spectrum observed in humans and suggests synergistic mechanisms involved, including thromboembolism and cerebral vasculitis, promoted by a systemic bacteremia-mediated inflammation.
感染性心内膜炎赘生物引发的栓塞事件通常被认为是导致其神经系统并发症的主要机制。病理生理学可能意味着存在其他现象，包括血管炎。本研究旨在明确感染性心内膜炎大鼠模型中的脑损伤谱。
金黄色葡萄球菌或粪肠球菌感染性心内膜炎的实验模型。比较感染性心内膜炎模型中观察到的神经病变与三种其他情况，即菌血症、非细菌性血栓性心内膜炎和健康对照。
一所大学医院的研究实验室。
雄性 Wistar 大鼠。
脑 MRI、神经病理学、星形胶质细胞和小胶质细胞免疫组化以及脑组织细菌研究用于表征神经病变。
在感染性心内膜炎组中，23 只大鼠中有 12 只（52%）至少有 1 个脑部病变，包括脑梗死（9/23，39%）和脑微出血（8/23，35%）。在感染性心内膜炎组中，神经病理学显示脑梗死（12/23，52%）、微出血（10/23，44%）和炎症过程（即包括脓肿、血管炎、脑膜脑炎和/或室管膜炎的细胞浸润；11/23，48%）。在菌血症组中，MRI 研究正常，神经病理学仅显示出血（11/11，18%）。非细菌性血栓性心内膜炎组的神经病理学模式与感染性心内膜炎组相似。免疫组化显示感染性心内膜炎组小胶质细胞激活更高（11/23，48%），与菌血症组（1/11，9%；p=0.03）和非细菌性血栓性心内膜炎组（0/7，0%；p=0.02）相比。
本感染性心内膜炎模型重现了人类观察到的神经系统病变谱，并提示包括血栓栓塞和脑血管炎在内的协同机制，这些机制可能由全身性菌血症介导的炎症引起。
