Assessment of Blood-Brain Barrier Function and the Neuroinflammatory Response in the Rat Brain by Using Cerebral Open Flow Microperfusion (cOFM) |
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| Authors: | Arijit Ghosh Thomas Birngruber Wolfgang Sattler Thomas Kroath Maria Ratzer Frank Sinner Thomas R. Pieber |
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| Affiliation: | 1. Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.; 2. HEALTH – Institute of Biomedicine and Health Sciences, Joanneum Research, Graz, Austria.; 3. Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria.; Universidade de São Paulo, Brazil, |
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| Abstract: | 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. |
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