Assessment of Blood-Brain Barrier Function and the Neuroinflammatory Response in the Rat Brain by Using Cerebral Open Flow Microperfusion (cOFM)

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.

Are Chronic Periodontitis and Gingivitis Associated with Dementia? A Nationwide, Retrospective, Matched-Cohort Study in Taiwan

“…These effects could be related to peripheral proinflammatory factors released by periodontal inflammatory mediators such as C-reactive protein, interleukin-6, haptoglobin, tumor necrosis factor-alpha, and fibrinogen [71,80,81]. Other studies have also shown that these proinflammatory factors may penetrate the blood-brain barrier, and that this may be the reason why local or systemic inflammatory mediators can influence the brain [82,83]. We, therefore, hypothesize that these proinflammatory factors may penetrate the blood-brain barrier during inflammatory conditions, resulting in neurodegenerative changes in the development of dementia.…”

Lipopolysaccharide-Induced Apoptosis of Astrocytes: Therapeutic Intervention by Minocycline

“…Lipopolysaccharide (LPS), a bacterial endotoxin is widely used to mimic systemic inflammatory conditions with activation of glial cells (microglia and astrocytes) in brain to synthesize and secrete a variety of neuroactive and neurotoxic molecules, interleukins and free radicals (Henry et al 2008;Ghosh et al 2014). Activated astrocytes proliferate and produce a variety of inflammatory mediators such as nitric oxide (NO), TNF-a, etc.…”

Early-life enteric infections: relation between chronic systemic inflammation and poor cognition in children

“…144 Recently, it was demonstrated that acute injection of a septic dose of LPS intraperitoneally could lead to breakdown of the blood-brain barrier and increased brain levels of proinflammatory cytokines with activated microglia in an experimental model. 145 Systemic LPS (indirectly, by inducing blood-brain barrier epithelial cells or proinflammatory cytokine release) could activate microglia and cause neuroinflammation in the adult 142 and aged brain. 146,147 This may predispose to neurodegeneration, 142 whereas aging reduces the responsiveness to the interleukin 4-induced M2 microglia phenotype.…”