Alterations in Peripheral Organs following Combined Hypoxemia and Hemorrhagic Shock in a Rat Model of Penetrating Ballistic-Like Brain Injury

Abstract

Polytrauma, with combined traumatic brain injury (TBI) and systemic damage are common among military and civilians. However, the pathophysiology of peripheral organs following polytrauma is poorly understood. Using a rat model of TBI combined with hypoxemia and hemorrhagic shock, we studied the status of peripheral redox systems, liver glycogen content, creatinine clearance, and systemic inflammation. Male Sprague-Dawley rats were subjected to hypoxemia and hemorrhagic shock insults (HH), penetrating ballistic-like brain injury (PBBI) alone, or PBBI followed by hypoxemia and hemorrhagic shock (PHH). Sham rats received craniotomy only. Biofluids and liver, kidney, and heart tissues were collected at 1 day, 2 days, 7 days, 14 days, and 28 days post-injury (DPI). Creatinine levels were measured in both serum and urine. Glutathione levels, glycogen content, and superoxide dismutase (SOD) and cytochrome C oxidase enzyme activities were quantified in the peripheral organs. Acute inflammation marker serum amyloid A-1 (SAA-1) level was quantified using western blot analysis. Urine to serum creatinine ratio in PHH group was significantly elevated on 7-28 DPI. Polytrauma induced a delayed disruption of the hepatic GSH/GSSG ratio, which resolved within 2 weeks post-injury. A modest decrease in kidney SOD activity was observed at 2 weeks after polytrauma. However, neither PBBI alone nor polytrauma changed the mitochondrial cytochrome C oxidase activity. Hepatic glycogen levels were reduced acutely following polytrauma. Acute inflammation marker SAA-1 showed a significant increase at early time-points following both systemic and brain injury. Overall, our findings demonstrate temporal cytological/tissue level damage to the peripheral organs due to combined PBBI and systemic injury.

Potential Immune Indicators for Predicting the Prognosis of COVID-19 and Trauma: Similarities and Disparities

“…Serum levels of Amyloid A (AA) during 6 to 24 hours posttrauma have been suggested as a prognostic indicator to predict poor outcomes in patients (75,76). Another study showed a positive association between severity of injuries and increased AA concentrations in blood circulation after trauma (77).…”

“…Moreover, an increase in serum concentration of this cytokine at days 4 to 6 after the onset of disease symptoms, which decreases over the next few days, is associated with good prognosis (88). It appears a high expression of IFN-g at admission, which continues for 3 to 4 weeks, could cause negative consequences due to over-activity in the immune (30,32,33,37,80), PCT (30,33,38,(51)(52)(53)55), ferritin (33,68) and SAA (73,75,76,78) system, inducing ACE2 expression (the binding site for SARS-CoV-2) and promoting virus replication (87). Anti-IFN-I autoantibodies have recently been detected in COVID-19 and are associated with poor prognosis of the disease.…”

Cryptotanshinone ameliorates hemorrhagic shock-induced liver injury via activating the Nrf2 signaling pathway

“…The treatment of CTS in higher concentrations effectively alleviated the above phenomenon. In the preliminary stage of the study, we found that most of the researchers used male animals to build this model [26,27,[34][35][36], thus we speculate that there may be no gender difference in HS-induced liver injury. In addition, there are hormonal changes in the physiological cycle of female rats and mice, thus, in order to avoid the uncontrollable factors, we chose male rats for modeling.…”

The Clinical Differences of Patients With Traumatic Brain Injury in Plateau and Plain Areas

“…For another, the level of creatinine and urea nitrogen was higher in patients with TBI in plateau areas, and the percentage of renal injury was higher but without significance. Previous studies have demonstrated that multiple systemic and local changes occur following TBI, including liver and renal injury ( 5 , 7 , 17 – 20 ). Concerning the liver, TBI can modulate the synthesis of acute-phase proteins by hepatocytes and exert the neuro-innate immune response, which further induces acute liver injury with increased expression of oxidative stress markers and mitochondrial dysfunction within hepatocytes ( 5 , 17 , 18 ).…”

“…Previous studies have demonstrated that multiple systemic and local changes occur following TBI, including liver and renal injury ( 5 , 7 , 17 – 20 ). Concerning the liver, TBI can modulate the synthesis of acute-phase proteins by hepatocytes and exert the neuro-innate immune response, which further induces acute liver injury with increased expression of oxidative stress markers and mitochondrial dysfunction within hepatocytes ( 5 , 17 , 18 ). As for the kidney, TBI may cause acute kidney injury through increased sympathetic nervous system activity and plasma catecholamines, systolic hypertension, and hypovolemia by the brain–kidney crosstalk ( 7 , 19 – 21 ).…”