Inosine attenuates post-stroke neuroinflammation by modulating inflammasome mediated microglial activation and polarization

Biochim Biophys Acta Mol Basis Dis. 2023 Jun 5:166771. doi: 10.1016/j.bbadis.2023.166771. Online ahead of print.ABSTRACTTo date, various agents and molecules have been developed to treat post-stroke neuroinflammation; however, none of them are clinically successful. Post-stroke neuroinflammation is primarily attributed to microglial polarization as the generation of inflammasome complexes shifts microglia to their M1 phenotype and regulate the downstream cascade. Inosine, an adenosine derivative reported to maintain cellular energy homeostasis in stressed condition. Although, the exact mechanism is still unexplored, various studies have reported that it can stimulate axonal sprouting in different neurodegenerative diseases. Hence, our present study aims to decipher the molecular mechanism of inosine mediated neuroprotection by modulating inflammasome signaling towards altered microglial polarization in ischemic stroke. Inosine was administered intraperitoneally to male Sprague Dawley rats at 1 h post ischemic stroke and were further evaluated for neurodeficit score, motor coordination and long-term neuroprotection. Brains were harvested for infarct size estimation, biochemical assays and molecular studies. Inosine administration at 1 h post ischemic stroke decreased infarct size, neurodeficit score, and improved motor co-ordination. Normalization of biochemical parameters were achieved in the treatment groups. Microglial polarization towards its anti-inflammatory phenotype an...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Source Type: research