Abstract
This paper explored the potential mediating role of hydrogen sulfide (H2S) and the oxytocin (OT) systems in hemorrhagic shock (HS) and/or traumatic brain injury (TBI). Morbidity and mortality after trauma mainly depend on the presence of HS and/or TBI. Rapid “repayment of the O2 debt” and prevention of brain tissue hypoxia are cornerstones of the management of both HS and TBI. Restoring tissue perfusion, however, generates an ischemia/reperfusion (I/R) injury due to the formation of reactive oxygen (ROS) and nitrogen (RNS) species. Moreover, pre-existing-medical-conditions (PEMC’s) can aggravate the occurrence and severity of complications after trauma. In addition to the “classic” chronic diseases (of cardiovascular or metabolic origin), there is growing awareness of psychological PEMC’s, e.g., early life stress (ELS) increases the predisposition to develop post-traumatic-stress-disorder (PTSD) and trauma patients with TBI show a significantly higher incidence of PTSD than patients without TBI. In fact, ELS is known to contribute to the developmental origins of cardiovascular disease. The neurotransmitter H2S is not only essential for the neuroendocrine stress response, but is also a promising therapeutic target in the prevention of chronic diseases induced by ELS. The neuroendocrine hormone OT has fundamental importance for brain development and social behavior, and, thus, is implicated in resilience or vulnerability to traumatic events. OT and H2S have been shown to interact in physical and psychological trauma and could, thus, be therapeutic targets to mitigate the acute post-traumatic effects of chronic PEMC’s. OT and H2S both share anti-inflammatory, anti-oxidant, and vasoactive properties; through the reperfusion injury salvage kinase (RISK) pathway, where their signaling mechanisms converge, they act via the regulation of nitric oxide (NO).
Highlights
Polytrauma–Hemorrhage and Brain InjuryThe presence of hemorrhage and traumatic brain injury (TBI) are the main determiners of morbidity and mortality after poly-trauma
It should be noted that the actual presence of early life stress (ELS)/adverse childhood experience (ACE) may be of particular importance for the effectiveness of intranasal OT application: if pigs were repetitively treated immediately postnatal with intranasal OT, stress tolerance was worsened
In line with the CSE−/−-related development of arterial hypertension, we showed that CSE−/− mice undergoing pre-traumatic cigarette smoke exposure to induce chronic obstructive pulmonary disease (COPD) presented with higher mean arterial pressures (MAP) during the acute phase after blunt chest trauma despite more pronounced metabolic depression as evidenced by reduced capacity to maintain normoglycemia [127]
Summary
The presence of hemorrhage and traumatic brain injury (TBI) are the main determiners of morbidity and mortality after poly-trauma. Vascular comorbid patients are characterized by chronic hyper-inflammation, excess ROS formation, and mitochondrial dysfunction [31,32] and, patients with underlying cardiovascular co-morbidity (hypertension, coronary artery disease (CAD), congestive heart failure) present with a several-fold higher risk of MOF and mortality after HS and/or TBI [28,30] This is in line with the worse outcome of TBI in the elderly [33], which in mice was shown to result from more pronounced oxidative stress [34]. A reciprocal relationship between TBI and psychological stress was demonstrated in rats: posttraumatic behavioral disturbances were directly related to mitochondrial dysfunction [80], and repetitive psychological stress in turn amplified the effect of TBI on mitochondrial respiratory chain protein expression [81]
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