Cranial Osteopathic Manipulative Medicine Enhances Brain Fluid Flow Alleviating Neuroinflammation - PROJECT SUMMARY/ABSTRACT Osteopathic manipulative medicine (OMM) has been used clinically to improve the quality of life for several medical conditions and injuries; however, limited data is available on the brain’s response to this innovative treatment. Cranial OMM (cOMM) involves the gentle application of manual force to the head and the axial spine, subsequently affecting the patient by releasing soft tissue restrictions. This technique enhances motion of the tissues and fluid flow through the brain through natural channels and helps to regulate tissue fluid flows in the body as well as balancing the autonomic nervous system. We expect that cOMM will help to clear inflammatory molecules from the brain in clinical challenges such as traumatic brain injury (TBI). To elucidate the mechanistic effects of this integrative health approach utilizing cOMM, studies will focus on the cholinergic system. Multiple studies and preliminary data consistently demonstrate that significant dysregulation in cholinergic neurotransmission mechanisms occurs in injured rodent brains, which is intricately linked to neurological phenotypes such as cognitive impairment and other neurologic dysfunctions. This underscores the profound importance of exploring the therapeutic potential of cOMM in mitigating these adverse effects. There is a critical need to ascertain the interactions of physiological (e.g., neural, musculoskeletal, immune) and psychological systems in response to force-based interventions such as cOMM. Using TBI as a platform, the broad, long-term objective of this study is to evaluate the neuro-biological effect of cOMM as a non-invasive approach to alleviate symptoms and enhance neural tissue recovery. Using a preclinical model, we will investigate if cOMM can mitigate behavioral patterns seen following repetitive closed head brain injury. We will use biomedical MR imaging and molecular biology techniques to measure brain fluid flow and track inflammation with and without cOMM treatment. Our study will include both males and females because it has been shown that neurological symptoms, severity of injury and hence possibly changes in fluid flow in the brain are different between sexes, which will allow refinement of cOMM treatment depending on sex. Collectively, we will be the first to provide evidence for the clinically observed effects following cOMM when used as an intervention for TBI and resulting acute and chronic symptoms.