B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice

What the hell are your doctors and stroke hospital doing to ensure that human testing occurs? Waiting for SOMEONE ELSE TO SOLVE THE PROBLEM is pure incompetency.  I'd suggest having survivors run that stroke hospital. We finally would get stroke solved. Current stroke leaders have been failing for 50+ years, we can't do worse. 

B cells migrate into remote brain areas and support neurogenesis and functional recovery after focal stroke in mice

Sterling B. Ortegaa,b,c,1, Vanessa O. Torresb,c,1, Sarah E. Latchneyd,e, Cody W. Whooleryd, Ibrahim Z. Noorbhaib,c, Katie Poinsatteb,c, Uma M. Selvarajb,c, Monica A. Bensonb,c, Anouk J. M. Meeuwissenb,c, Erik J. Plautzb,c, Xiangmei Kongb,c, Denise M. Ramirezb,c, Apoorva D. Ajayb,c, Julian P. Meeksb,c,f, Mark P. Goldbergb,c, Nancy L. Monsonb,c, Amelia J. Eischd,g,h, and Ann M. Stoweb,c,i,2
aDepartment of Pathology, University of Iowa, Iowa City, IA 52242; bDepartment of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390; cPeter O’Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX 75390; dDepartment of Psychiatry, UT Southwestern Medical Center, Dallas, TX 75390; eDepartment of Biology, St. Mary’s College of Maryland, St. Mary’s City, MD 20686; fDepartment of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390; gDepartment of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; hDepartment of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, Philadelphia, PA 19104; and iDepartment of Neurology, University of Kentucky, Lexington, KY 40506
Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved January 16, 2020 (received for review August 1, 2019)
Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified post stroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20+ (hCD20+) transgenic mice to continuously deplete hCD20+-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) litter mates also receiving rituximab. B cell depletion reduced stroke induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain.