Region-specific and activity-dependent regulation of SVZ neurogenesis and recovery after stroke

You can have your doctor analyze these 10 pages and come back to you with stroke rehab protocols. I don't care that this is in mice, waiting for human trials will take place after you are dead.

Region-specific and activity-dependent regulation of SVZ neurogenesis and recovery after stroke

Huixuan Lianga, Handi Zhaoa, Amy Gleichmana, Michal Machnickia, Sagar Telanga, Sydney Tanga, Mary Rshtounia,Jack Ruddella, and S. Thomas Carmichaela,1aDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095Edited by Anders Björklund, Lund University, Lund, Sweden, and approved May 13, 2019 (received for review July 10, 2018)
 Stroke is the leading cause of adult disability. Neurogenesis after stroke is associated with repair; however, the mechanisms regulating post stroke neurogenesis and its functional effect remain unclear. Here, we investigate multiple mechanistic routes of induced neurogenesis in the poststroke brain, using both a fore-limb overuse manipulation that models a clinical neurorehabilitation paradigm, as well as local manipulation of cellular activity in the periinfarct cortex. Increased activity in the forelimb peri-infarct cortex via either modulation drives increased subventricular zone (SVZ) progenitor proliferation, migration, and neuronal maturation in periinfarct cortex. This effect is sensitive to com-petition from neighboring brain regions. By using orthogonal tract tracing and rabies virus approaches in transgenic SVZ lineage tracing mice, SVZ-derived neurons synaptically integrate into the perinfarct cortex; these effects are enhanced with forelimb over-use. Synaptic transmission from these newborn SVZ-derived neurons is critical for spontaneous recovery after stroke, as tetanus neurotoxin silencing specifically of the SVZ-derived neurons disrupts the formation of these synaptic connections and hinders functional recovery after stroke. SVZ-derived neurogenesis after stroke is activity-dependent, region-specific, and sensitive to modulation, and the synaptic connections formed by these newborn cells are functionally critical for post stroke recovery.