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肺炎球菌性脑膜炎大鼠脑内抑郁样行为和促炎细胞因子水平。

Depressive-like-behavior and proinflamatory interleukine levels in the brain of rats submitted to pneumococcal meningitis.

机构信息

Laboratory of Experimental Microbiology and National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000 Criciúma, SC, Brazil.

出版信息

Brain Res Bull. 2010 Jul 30;82(5-6):243-6. doi: 10.1016/j.brainresbull.2010.04.015. Epub 2010 May 5.

Abstract

Bacterial meningitis due to Streptococcus pneumoniae is associated with a significant mortality rate and persisting neurologic sequelae including sensorymotor deficits, seizures, and impairments of learning and memory. The presence of proliferating bacteria within the subarachnoid and ventricular space compartments triggers an intense inflammatory host response. Proinflammatory mediators released in the process include tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and all of which have been shown to contribute to the development of brain injury in bacterial meningitis. The animals underwent a magna cistern tap receiving either 10muL sterile saline as a placebo or an equivalent volume of a S. pneumoniae suspension at the concentration 5x10(9)cfu/mL. Ten days after induction we evaluated depressive-like behavior by using the forced swimming test and verified the levels of the TNF-alpha, IL-1beta, IL-6 and CINC-1 in the brain of rats induced to pneumococcal meningitis. In the forced swimming test we observed a significant increase in the immobility time in the meningitis group compared to the sham group (p<0.05). The TNFlevels were found increased in the prefrontal cortex (p<0.05, F=4.921), but not hippocampus. The IL-6, CINC-1 and IL-1beta levels presented no alteration in both prefrontal cortex and hippocampus 10 days after meningitis induction by S. pneumoniae. These findings suggest that the meningitis model could be a good research tool for the study of the biological mechanisms involved in the behavioral alterations secondary to pneumococcal meningitis.

摘要

肺炎链球菌引起的细菌性脑膜炎与高死亡率和持续存在的神经后遗症相关,包括感觉运动缺陷、癫痫发作以及学习和记忆障碍。在蛛网膜下腔和脑室空间中增殖的细菌会引发强烈的炎症宿主反应。在此过程中释放的促炎介质包括肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6,所有这些都被证明有助于细菌性脑膜炎的脑损伤发展。动物接受了脑池穿刺,接受了 10μL 无菌生理盐水作为安慰剂或相当于 5x10(9)cfu/mL 肺炎链球菌混悬液的体积。诱导后 10 天,我们通过强迫游泳试验评估了抑郁样行为,并验证了诱导肺炎球菌性脑膜炎大鼠大脑中 TNF-α、IL-1β、IL-6 和 CINC-1 的水平。在强迫游泳试验中,我们观察到脑膜炎组的不动时间明显长于假手术组(p<0.05)。在额皮质(p<0.05,F=4.921)中发现 TNF 水平升高,但海马体中没有升高。肺炎链球菌诱导脑膜炎 10 天后,在额皮质和海马体中,IL-6、CINC-1 和 IL-1β 水平均无变化。这些发现表明,该脑膜炎模型可能是研究与肺炎球菌性脑膜炎相关的行为改变的生物学机制的良好研究工具。

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