Enriched environment downregulates macrophage migration inhibitory factor and increases parvalbumin in the brain following experimental stroke

Housing rodents in an enriched environment (EE) following experimental stroke enhances neurological recovery. Understanding the underlying neural cues may provide the basis for improving stroke rehabilitation. We studied the contribution of brain macrophage migration inhibitory factor (MIF) to functional recovery after permanent middle cerebral artery occlusion (pMCAo) in rats. In the cerebral cortex, MIF is predominantly found in neurons, particularly in parvalbumin interneurons. Following pMCAo, MIF increases around the infarct core, where it is located to neurons and astrocytes. Housing rats in an EE after pMCAo resulted in a decrease of MIF protein levels in peri-infarct areas, which was accompanied by an increase in parvalbumin immunoreactive interneurons. Our data suggest that MIF is part of a signaling network involved in brain plasticity, and elevated neuronal and/or astrocytic MIF levels repress the recovery of sensory–motor function after stroke. Downregulating MIF could constitute a new therapeutic approach to promote recovery after stroke.

Research Highlights
► Cortical parvalbumin (PV)-containing interneurons are rich in MIF.
► MIF-immunoreactivity increases in the peri-infarct region after pMCAo.
► MIF is expressed in peri-infarct neurons and particularly in reactive astrocytes.
► Enriched environment (EE) decreases MIF protein levels in the brain after pMCAo.
► EE increases the density of PV-cells in the peri-infarct cortex after pMCAo.