Role of B cells and the aging brain in stroke recovery and treatment.

As mitigation of brain aging continues to be a key public health priority, a wholistic and comprehensive consideration of the aging body has identified immunosenescence as a potential contributor to age-related brain injury and disease. Importantly, the nervous and immune systems engage in bidirectional communication and can exert profound influence on each other. Emerging evidence supports numerous impacts of innate, inflammatory immune responses and adaptive T cell-mediated immunity in neurological function and diseased or injured brain states, such as stroke. Indeed, a growing body of evidence supports key impacts of brain-resident immune cell activation and peripheral immune infiltration in both the post-stroke acute injury phase and the long-term recovery period. As such, modulation of the immune system is an attractive strategy for novel therapeutic interventions for a devastating age-related brain injury for which there are few readily available neuroprotective treatments or neurorestorative approaches. However, the role of B cells in the context of brain function, and specifically in response to stroke, has not been thoroughly elucidated and remains controversial, leaving our understanding of neuroimmune interactions incomplete. Importantly, emerging evidence suggests that B cells are not pathogenic contributors to stroke injury, and in fact may facilitate functional recovery, supporting their potential value as novel therapeutic targets. By summarizing the current knowledge of the role of B cells in stroke pathology and recovery and interpreting their role in the context of their interactions with other immune cells as well as the immunosenescence cascades that alter their function in aged populations, this review supports an increased understanding of the complex interplay between the nervous and immune systems in the context of brain aging, injury, and disease.

Autoantibody-mediated bladder dysfunction in type 1 diabetes.

Bladder dysfunction is a common complication of diabetic autonomic neuropathy; however, its cause remains uncertain. We have recently identified a novel IgG autoantibody (Ab) in patients with type 1 diabetes that acts as an agonist at the dihydropyridine (DHP) site of L-type voltage-gated calcium channels (VGCC), disrupting neuronal regulation of visceral smooth muscle. In the present study, passive transfer to mice of IgG from patients with type 1 diabetes was used to investigate the role of anti-VGCC Abs in mediating diabetic bladder dysfunction. Injection of mice with diabetic immunoglobulin (IgG) with anti-VGCC activity induced features of an overactive bladder, including phasic detrusor contractions and a loss of bladder wall compliance. The bladder overactivity is mimicked by the DHP agonist Bay K8644, reversed by the DHP antagonist nicardipine, but is insensitive to the motor nerve blocker tetrodotoxin, indicating that the anti-VGCC Ab acts at the level of the bladder detrusor itself. This study reports the first evidence of Ab-mediated bladder dysfunction in type 1 diabetes, which may be part of a wider spectrum of smooth muscle and cardiac abnormalities.