Three Days Delayed Recanalization Improved Neurological Function in pMCAO Rats by Increasing M2 Microglia —Possible Involvement of the IL-4R/STAT6/PPARγ Pathway

AbstractCurrent approved therapies for acute ischemic stroke have a restricted therapeutic time window. Delayed recanalization, which has been utilized clinically in patients who have missed the time window for administration, may be a promising alternative for stroke patients. However, the underlying molecular mechanisms remain undiscovered. Herein, we hypothesized that delayed recanalization would increase M2 microglial polarization through the IL-4R (interleukin-4 receptor)/STAT6 (signal transducer and activators of transcription 6)/PPAR γ (peroxisome proliferator–activated receptor γ) pathway, subsequently promoting stroke recovery in rats. The permanent middle cerebral artery occlusion (pMCAO) model was induced via intravascular filament insertion. Recanalization was induced by withdrawing the filament at 3 days after MCAO (r MCAO). Interleukin (IL)-4 was administered intranasally at 3 days after pMCAO. AS1517499, a specific STAT6 inhibitor, was administered intranasally at 3 days after MCAO induction. Immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, volumetric measurements of brain infarct, and neurological behavior tests were conducted. Delayed recanalization at 3 days after MCAO increased the polarization of M2 microglia, decreased inflammation, and improved neurological behavior. IL-4 treatment administered on the 3rd day after pMCAO increased M2 microglial polar ization, improved neurological behavior, and reduce...
Source: Translational Stroke Research - Category: Neurology Source Type: research