Ghosh Arijit, Birngruber Thomas, Sattler Wolfgang, Kroath Thomas, Ratzer Maria, Sinner Frank, Pieber Thomas R
Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
HEALTH - Institute of Biomedicine and Health Sciences, Joanneum Research, Graz, Austria.
PLoS One. 2014 May 22;9(5):e98143. doi: 10.1371/journal.pone.0098143. eCollection 2014.
Blood-brain barrier (BBB) impairment in systemic inflammation leads to neuroinflammation. Several factors including cytokines, chemokines and signal transduction molecules are implicated in BBB dysfunction in response to systemic inflammation. Here, we have adopted a novel in vivo technique; namely, cerebral open flow microperfusion (cOFM), to perform time-dependent cytokine analysis (TNF-alpha, IL-6 and IL-10) in the frontal cortex of the rat brain in response to a single peripheral administration of lipopolysaccharide (LPS). In parallel, we monitored BBB function using sodium fluorescein as low molecular weight reporter in the cOFM sample. In response to the systemic LPS administration, we observed a rapid increase of TNF-alpha in the serum and brain, which coincides with the BBB disruption. Brain IL-6 and IL-10 synthesis was delayed by approximately 1 h. Our data demonstrate that cOFM can be used to monitor changes in brain cytokine levels and BBB disruption in a rat sepsis model.
全身炎症反应中的血脑屏障（BBB）损伤会导致神经炎症。细胞因子、趋化因子和信号转导分子等多种因素与全身炎症反应时的血脑屏障功能障碍有关。在此，我们采用了一种新的体内技术，即脑开放流动微灌注（cOFM），来对大鼠脑额叶皮质进行时间依赖性细胞因子分析（肿瘤坏死因子-α、白细胞介素-6和白细胞介素-10），以响应单次外周注射脂多糖（LPS）。同时，我们在cOFM样本中使用荧光素钠作为低分子量报告物来监测血脑屏障功能。响应全身注射LPS，我们观察到血清和脑中肿瘤坏死因子-α迅速增加，这与血脑屏障破坏同时发生。脑白细胞介素-6和白细胞介素-10的合成延迟约1小时。我们的数据表明，cOFM可用于监测大鼠脓毒症模型中脑内细胞因子水平的变化和血脑屏障破坏情况。
