B-Cells in Stroke and Preconditioning-Induced Protection Against Stroke

It is well-understood that inflammation following stroke onset contributes to neuronal injury, blood–brain barrier (BBB) disruption, and functional deficits during recovery. But which leukocyte subsets critically contribute to injury, and more importantly which may be necessary for neurorepair, remains to be fully elucidated. One emerging concept is that B-cells, and specifically regulatory B-cells, exhibit the potential to contribute to anti-inflammatory, protective mechanisms during acute recovery. Unfortunately, few studies have investigated the role of B-cells during ischemic brain injury. This chapter reviews B-cell development and function, as well as the contribution of B-cells to pathology during other autoimmune diseases. This is followed by an overview of inflammatory mechanisms after stroke, with emphasis on a potential role for B-cells in post-stroke autoimmunity. Research will be summarized that highlights the role for B-cells in acute CNS neuroprotection after stroke, as well as new data suggesting that B-cells may be detrimental to long-term cognitive function in experimental stroke. Finally, this chapter will focus on preconditioning, a method by which non-injurious, noxious stimuli create an ischemia-tolerant phenotype to protect from stroke. Several preconditioning paradigms that affect B-cell function, including hypoxia, exercise, and exposure to lipopolysaccharide (LPS), will be reviewed, with an emphasis on the clinical relevance to populations at-risk for stroke. While more research is needed to clearly define the role of B-cells in post-stroke recovery, this chapter will highlight several mechanisms by which B-cells can directly influence recovery in the injured CNS.