Meningeal mast cells control brain-meningeal-brain axis 2150

Abstract Description Cerebrospinal fluid (CSF) plays a crucial role in maintaining brain physiology, and its disruption has been shown to be critical in the development of neurodegenerative and neuroinflammatory conditions, such as Alzheimer’s disease. Recently, novel anatomical structures termed arachnoid cuff exit (ACE) points have been characterized, which facilitate cerebrospinal fluid (CSF) outflow, while also allowing dural interstitial fluid (ISF) to flow back into the subarachnoid space. However, how CSF flow is regulated at ACE points remains unclear. This bidirectional flow raises the possibility that pathogens could exploit ACE points to invade the brain, increasing the risk of brain infections. Here, we show that dura mast cells located at ACE points, which upon degranulation impair CSF flow dynamics, through the release of histamine. Moreover, during bacterial meningitis, these meningeal mast cells help to recruit neutrophils and trap bacteria in the dura, limiting pathogen spread from the dura to the brain via ACE points. Our findings position dural mast cells as key regulators of meningeal immunity and CSF/ISF dynamics. Targeting these cells pharmacologically could represent a novel therapeutic strategy to enhance brain clearance and mitigate bacterial invasion of the brain. Funding Sources NIH (AI183879) and Cure Alzheimer’s Fund. Topic Categories Neuroimmunology (NEUR)