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

Bernard S Wilfred,Janice S Gilsdorf,Hye Mee Hwang,Sarah Urankar,Deborah A Shear,Sindhu K Madathil,Xiaofang Yang,Lai Yee Leung,Katherine Cardiff

doi:10.1089/neu.2019.6570

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.

Highlights

Combat-associated traumatic brain injury (TBI) commonly occurs in combination with peripheral organ damage
Food and water intake improved over time, it remained lower than baseline at all time-points
Compared with the sham and hemorrhagic shock (HH) animals, the food and water intake were significantly lower in the penetrating ballistic-like brain injury (PBBI) and PBBI combined with HH (PHH) groups at acute timepoints

Summary

Introduction

Combat-associated traumatic brain injury (TBI) commonly occurs in combination with peripheral organ damage. The majority of TBI-polytrauma studies have focused primarily on the cerebral changes following combined injuries.[1,2,3,4] Using a rat model of penetrating ballistic-like brain injury (PBBI) combined with hypoxemia and hemorrhagic shock (HH),[5,6] the current study examines pathological changes in the peripheral organs. Systemic hypoxemia and hypoperfusion reduce oxygen supply to the peripheral organs, leading to an energy deficit. Part of this deficit can be compensated for by the intracellular degradation of stored adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and adenosine monophosphate (AMP).[7] a persistent energy crisis will deplete ATP stores and lead to hepatic glycogenolysis.[8] hepatic glycogen content represents an indirect measurement of liver stress

Methods

Results

Discussion

Conclusion