In a groundbreaking discovery, the BrainRepair group found that MANF protein expression is initiated microglia/macrophage cells in human and rodent infarcted brains. “The shift in MANF protein expression after stroke in the brain is robust, the difference is like day and night”, says Mikko Airavaara.
Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF), a naturally occurring protein found in several tissues, has been identified to possess cytoprotective effects against various injuries, including cerebral ischemia. Previously, MANF protein expression was primarily associated with neurons in uninjured rodent brains. However, we have recently discovered a profound shift in its expression pattern during and after ischemic strokes. Our study showed as the infarct, or damaged area, in both human and rat brains progressed, MANF expression transitioned dramatically from neurons to inflammatory cells.
Specifically, intense MANF immunoreactivity was observed in phagocytic microglia/macrophages within the ischemic territory. In humans, this peak expression occurred at two weeks post-stroke, while in rat ischemic cortex, it was observed at one-week post-stroke. This revelation suggests that MANF plays a crucial role in modulating the inflammatory response following a stroke.
To further investigate the therapeutic potential of MANF, we conducted a series of experiments using systemic delivery of recombinant MANF in a rat model of cortical ischemic stroke. Intranasal administration of recombinant MANF led to a reduction in infarct volume and a decrease in the severity of neurological deficits. Additionally, intravenous delivery of recombinant MANF decreased pro-inflammatory cytokine levels and increased the levels of anti-inflammatory cytokine IL-10 in the infarcted cortex within one-day post-stroke.
This exciting breakthrough suggests that MANF protein could hold the key to regulating post-stroke inflammation. The ability of exogenously delivered MANF to modulate tissue recovery processes opens up new possibilities for stroke treatment and recovery.