PTP1B inhibitor alleviates deleterious microglial activation and neuronal injury after ischemic stroke by modulating the ER stress-autophagy axis via PERK signaling in microglia

Cerebral ischemia/reperfusion (IR) after ischemic stroke causes deleterious microglial activation. Protein tyrosine phosphatase 1B (PTP1B) exacerbates neuroinflammation, yet the effect of inhibition on activation and cerebral IR injury is unknown. A rat model was induced by middle artery occlusion (MCAO) reperfusion. The PTP1B inhibitor, sc-222227, administered intracerebroventricularly. Neurologic deficits, infarct volume, brain water content were examined. An in vitro oxygen glucose deprivation/reoxygenation (OGD/R) established primary microglia BV-2 cells. Microglial activation/polarization, endoplasmic reticulum (ER) stress, autophagy, apoptosis detected using western blot, immunohistology, ELISA, real-time PCR. interaction assessed a proximity ligation assay. results showed significant increase expression injury. Sc-222227 attenuated IR-induced activation, ER autophagy promoted M2 polarization. Upon OGD/R, sc-222227 mitigated inhibiting stress-dependent which abolished PERK PTP1B-phosphorylated protein significantly increased but decreased upon treatment. Finally, neuronal damage neurologic deficits Treatment targeting might be potential therapeutic strategy for