Chicago Sky Blue 6B Exerts Neuroprotective and Anti-inflammatory Effects
on Focal Cerebral Ischemia
Abstract
Background and Purpose. Brain ischemia is one of the leading
causes of death and long-term disability worldwide. Cessation of the
blood supply to the brain directly stimulates many pathological events,
including glutamate overload and neuroinflammation. Glial cell
activation occurs shortly after ischemia onset, resulting in the release
of proinflammatory cytokines and exacerbation of the detrimental effects
of neuroinflammation. Proinflammatory signals influence the infiltration
of a wide range of immune cells, including neutrophils, T cells and
monocytes/macrophages. In this study, we aimed to verify the potential
anti-inflammatory effect of Chicago Sky Blue 6B (CSB6B) in a rat model
of focal cerebral ischemia (90-minute middle cerebral artery occlusion).
Experimental approach. CSB6B was administered 2 h before
ischemia induction (pretreatment) or 1.5 h after reperfusion onset
(posttreatment). A model of ischemic preconditioning was used as the
comparator to pretreatment with CSB6B. Key Results
&Conclusions. The results of indicated that posttreatment with CSB6B
had profound anti-inflammatory effects that were associated with reduced
neurological deficits and a decreased infarct volume. At 24 h, 3 days
and 7 days after brain ischemia, CSB6B administration reduced the
protein levels of proinflammatory cytokines, such as Il1β, Il6, Il18 and
TNFα, in the cerebral cortex and the dorsal striatum. Treatment with
CSB6B also limited the scope of microglia and astrocyte activation and
the infiltration of immune cells. Implications. Taken together,
this study shows that compounds such as CSB6B might be promising
pharmacological tools; however, further studies on the improvements in
the drug-like properties of these compounds must be undertaken.