Making sense of gut feelings in the traumatic brain injury pathogenesis

Abstract

Traumatic brain injury (TBI) is a devastating condition which often initiates a sequel of neurological disorders that can last throughout lifespan. From metabolic perspective, TBI also compromises systemic physiology including the function of body organs with subsequent malfunctions in metabolism. The emerging panorama is that the effects of TBI on the periphery strike back on the brain and exacerbate the overall TBI pathogenesis. An increasing number of clinical reports are alarming to show that metabolic dysfunction is associated with incidence of long-term neurological and psychiatric disorders. The autonomic nervous system, associated hypothalamic-pituitary axis, and the immune system are at the center of the interface between brain and body and are central to the regulation of overall homeostasis and disease. We review the strong association between mechanisms that regulate cell metabolism and inflammation which has important clinical implications for the communication between body and brain. We also discuss the integrative actions of lifestyle interventions such as diet and exercise on promoting brain and body health and cognition after TBI.

Association of Traumatic Brain Injury With the Risk of Developing Chronic Cardiovascular, Endocrine, Neurological, and Psychiatric Disorders

“… 22 Recent clinical and experimental studies suggest TBI may alter systemic metabolomic, gut flora, and immune pathways. 23 , 24 , 25 Therefore, the higher risk of comorbidities after TBI likely represents a combination of direct (hormonal and inflammatory changes caused by injury) and indirect factors (psychosocial risk factors).…”

Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits

“…Preclinical and clinical studies indicate that TBI causes structural and functional damage to the GI tract [ 66 , 67 ]. In rodents, TBI results in mucosal injury and impaired barrier function in the small intestine up to 72 h after injury [ 68 – 70 ] and 28 days after injury in the colon [ 24 ].…”

Gene Expression Signature of Traumatic Brain Injury

“…After TBI, peripheral blood leukocytes increased significantly, releasing complement factors and proinflammatory cytokines (Dalle Lucca et al, 2012 ). The sustained up-regulation of various cytokines is associated with changes in blood–brain barrier permeability, edema formation, and neurological deficits (Royes and Gomez-Pinilla, 2019 ). Interferon-γ can regulate neuronal networks and is associated with more severe disability in the acute phase after brain injury (Kramer et al, 2019 ).…”