The brain is in principle capable of far more repair than it actually undertakes in practice. This is generally true of most tissues, since the processes and pathways of developmental growth still exist. New neurons can be produced by neural stem cells, and the synaptic connections between neurons can be rearranged to bypass damage, where possible. It is all a matter of finding the right points of control for cellular activities. With that in mind, researchers here demonstrate a way to upregulate neuroplasticity and show that, this approach produces improved function in mice, even comparatively late in the treatment of stroke damage.
In addition to neuroprotective strategies, neuroregenerative processes could provide targets for stroke recovery. However, the upregulation of inhibitory chondroitin sulfate proteoglycans (CSPGs) impedes innate regenerative efforts. Here, we examine the regulatory role of PTPσ (a major proteoglycan receptor) in dampening post-stroke recovery. Use of a receptor modulatory peptide (a mimetic of the PTPσ regulatory wedge region with a TAT domain to facilitate membrane penetration) or PTPσ gene deletion leads to increased neurite outgrowth and enhanced neural stem cell migration in vitro.
Post-stroke ISP treatment results in increased axonal sprouting as well as neuroblast migration deeply into the lesion scar with a transcriptional signature reflective of repair. Lastly, peptide treatment post-stroke (initiated acutely or more chronically at 7 days) results in improved behavioral recovery in both motor and cognitive functions. Therefore, we propose that CSPGs induced by stroke play a predominant role in the regulation of neural repair and that blocking CSPG signaling pathways will lead to enhanced neurorepair and functional recovery in stroke.