Enriched housing down-regulates the Toll-like receptor 2 response in the mouse brain after experimental stroke

Abstract Post-ischemic inflammation plays an important role in the evolution of brain injury, recovery and repair after stroke. Housing rodents in an enriched environment provides multisensory stimulation to the brain and enhances functional recovery after experimental stroke, also depressing the release of cytokines and chemokines in the peri-infarct. In order to identify targets for late stroke treatment, we studied the dynamics of inflammation and the contribution of resident Toll-like receptor 2 (TLR2) expressing microglia cells. We took advantage of the biophotonic/bioluminescent imaging technique using the reporter mouse-expressing luciferase and GFP reporter genes under transcriptional control of the murine TLR2 promoter (TLR2-luc/GFP mice) for non-invasive in vivo analysis of TLR2 activation/response in photothrombotic stroke after differential housing. Real-time imaging at 1 day after stroke, revealed up-regulation of TLR2 in response to photothrombotic stroke that subsequently declined over time of recovery (14 days). The inflammatory response was persistently down-regulated within days of enriched housing, enhancing recovery of lost sensori-motor function in TLR2-luc mice without affecting infarct size. The number of YM1-expressing microglia in the peri-infarct and areas remote from the infarct was also markedly attenuated. Using a live imaging approach, we demonstrate that multisensory stimulation rapidly, persistently and generally attenuates brain inflammation after experimental stroke, reducing the TLR2 response and leading to improved neurological outcome. TLR2-expressing microglia cells may provide targets for new stroke therapeutics.