Bidirectional Brain-Systemic Interactions and Outcomes After TBI

Abstract

Traumatic brain injury (TBI) is a debilitating disorder associated with chronic progressive neurodegeneration and long-term neurological decline. Importantly, there is now substantial and increasing evidence that TBI can negatively impact systemic organs, including the pulmonary, gastrointestinal (GI), cardiovascular, renal, and immune system. Less well appreciated, until recently, is that such functional changes can affect both the response to subsequent insults or diseases, as well as contribute to chronic neurodegenerative processes and long-term neurological outcomes. In this review, we summarize evidence showing bidirectional interactions between the brain and systemic organs following TBI and critically assess potential underlying mechanisms.

Keywords: bidirectional; microglia; neuroinflammation; systemic; traumatic brain injury.

Figure 1:. Bi-directional effects of TBI and systemic organs.

TBI can induce lung and intestinal injury (right-side and bottom insets, respectively). This in turn can lead to organ dysfunction and subsequent increases in systemic inflammatory responses including EV release. Subsequent bacterial insults to both the lung and gut may result in exacerbation of TBI-induced deficits including neuroinflammation, neurodegeneration and neurological decline. In addition, TBI can result in cardiac, hepatic and renal dysfunction which may increase mortality (left-side column); however, the subsequent effects on long-term neurological function remain to be determined. Abbreviations: Traumatic brain injury (TBI); Extracellular vesicles (EV); Left ventricular ejection fraction (LVEF); Serum amyloid A (SSA).

Figure 2:. TBI-induced alterations in systemic and central immune function.

During the early stages of TBI, alterations can emerge in the systemic innate and adaptive immune responses that can in turn alter TBI-induced microglia responses and subsequent neurodegenerative processes. In addition, TBI can induce late changes in systemic immune responses including altered bone-marrow-derived myeloid cell function, which may in turn alter chronic microglial responses and neurodegenerative processes. Abbreviations: Traumatic brain injury (TBI); Reactive oxygen species (ROS); C-C chemokine receptor 2 (CCR2).