Brandt Christian T, Holm David, Liptrot Matthew, Ostergaard Christian, Lundgren Jens D, Frimodt-Møller Niels, Skovsted Ian C, Rowland Ian J
National Center for Antimicrobials and Infection Control, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
J Infect Dis. 2008 Jan 15;197(2):235-44. doi: 10.1086/524874.
Bacteremia plays a major role in the outcome of pneumococcal meningitis. This experimental study investigated how bacteremia influences the pathophysiologic profile of the brain.
Rats with Streptococcus pneumoniae meningitis were randomized to 1 of 3 groups of infected study rats: (1) rats with attenuated bacteremia resulting from intravenous injection of serotype-specific pneumococcal antibody, (2) rats with early-onset bacteremia resulting from concomitant intravenous infection, or (3) a meningitis control group. The blood-brain barrier (BBB) breakdown, ventricle size, brain water distribution, and brain pathologic findings were analyzed using magnetic resonance morphological and functional imaging. Laboratory data and clinical disease scores were obtained.
Attenuation of the bacteremic component of pneumococcal meningitis improved clinical disease symptoms and significantly reduced ventricle expansion and BBB breakdown (P< .05). Early-onset bacteremia did not further increase ventricle size or BBB leakage. Significantly increased brain edema developed among rats with both attenuated and early-onset bacteremia (P< .05). Focal brain pathologic findings were unaffected by bacteremia and were found to be associated with cerebrospinal fluid inflammation.
Although brain lesions appear to result from local meningeal infection, systemic infection significantly contributes to clinical disease presentation and the pathophysiology of BBB breakdown and ventricle expansion. The different end points affected by the systemic and local infectious processes should be addressed in future studies.
菌血症在肺炎球菌性脑膜炎的转归中起主要作用。本实验研究探讨了菌血症如何影响脑部的病理生理特征。
将患有肺炎球菌性脑膜炎的大鼠随机分为3组受感染研究大鼠中的1组:(1)通过静脉注射血清型特异性肺炎球菌抗体导致菌血症减弱的大鼠;(2)通过同时静脉感染导致早期菌血症的大鼠;或(3)一个脑膜炎对照组。使用磁共振形态学和功能成像分析血脑屏障(BBB)破坏、脑室大小、脑水分布和脑病理结果。获取实验室数据和临床疾病评分。
肺炎球菌性脑膜炎菌血症成分的减弱改善了临床疾病症状,并显著减少了脑室扩张和BBB破坏(P<0.05)。早期菌血症并未进一步增加脑室大小或BBB渗漏。菌血症减弱和早期菌血症的大鼠中均出现显著增加的脑水肿(P<0.05)。局灶性脑病理结果不受菌血症影响,且发现与脑脊液炎症有关。
尽管脑损伤似乎由局部脑膜感染引起,但全身感染对临床疾病表现以及BBB破坏和脑室扩张的病理生理学有显著影响。全身和局部感染过程影响的不同终点应在未来研究中加以探讨。