Inosine administration following ischemic stroke regulates inflammasome mediated microglial polarization
Pallab Bhattacharya1, Deepaneeta Sarmah2, Aishika Datta2
1National Institute of Pharmaceutical Education and Research (NIPER),Ahmedabad., 2Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER),Ahmedabad.
Objective:
The present study aims to decipher the molecular mechanism of Inosine mediated neuroprotection via regulating activated inflammasome mediated microglial polarization in rodent model of ischemic stroke.
Background:
Neuroinflammation is attributed to microglial polarization following stroke. The outcome of M1 phenotype depends on the activation of inflammasome that facilitates caspase-1 mediated pro-inflammatory response towards neuro-inflammation. Inosine, an adenosine derivative, is reported to maintain cellular energy homeostasis during cellular stress. It also stimulate axonal sprouting and improves motor-coordination in neurodegenerative diseases.
Design/Methods:
Inosine was administered to male SD rats at 60 mins post stroke in rodents. Rats were evaluated for neurodeficit score and motor coordination. Brains were harvested for infarct size estimation, biochemical estimations, and molecular assays for the evaluation of neuroprotective effects of Inosine.
Results:
Inosine therapy renders neuroprotection as evident by reduced infarct size, improved motor and functional outcome and normalization of biochemical parameters. Microglial polarization towards its anti-inflammatory phenotype and modulation of inflammation were evident by relevant gene and protein expression studies.
Conclusions:
This study provides preliminary evidence of the role of Inosine in microglial polarization modulation towards its anti-inflammatory form via regulating inflammasome activation post-stroke.