Previous physical exercise alters the hepatic profile of oxidative‐inflammatory status and limits the secondary brain damage induced by severe traumatic brain injury in rats

Abstract

Although systemic responses have been described after traumatic brain injury (TBI), little is known regarding potential interactions between brain and peripheral organs after neuronal injury. Accordingly, we aimed to investigate whether a peripheral oxidative/inflammatory response contributes to neuronal dysfunction after TBI, as well as the prophylactic role of exercise training. Animals were submitted to fluid percussion injury after 6 weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha and ATP-binding cassette transporter, and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α and interleukin (IL)-6 expression per se in liver. Interestingly, exercise training protected against hepatic inflammation (COX-2, iNOS, TNF-α and IL-6), oxidative stress (decreases in non-protein sulfhydryl and glutathione, as well as increases in 2',7'-dichlorofluorescein diacetate oxidation and protein carbonyl), which altered hepatic redox status (increases in myeloperoxidase and superoxide dismutase activity, as well as inhibition of catalase activity) mitochondrial function (decreases in methyl-tetrazolium and Δψ, as well as inhibition of citrate synthase activity) and ion gradient homeostasis (inhibition of Na ,K -ATPase activity inhibition) when analysed 24 h after TBI. Previous exercise training also protected against dysglycaemia, impaired hepatic signalling (increase in phosphorylated c-Jun NH2-terminal kinase, phosphorylated decreases in insulin receptor substrate and phosphorylated AKT expression), high levels of circulating and neuronal cytokines, the opening of the blood-brain barrier, neutrophil infiltration and Na ,K -ATPase activity inhibition in the ipsilateral cortex after TBI. Moreover, the impairment of protein function, neurobehavioural (neuromotor dysfunction and spatial learning) disability and hippocampal cell damage in sedentary rats suggests that exercise training also modulates peripheral oxidative/inflammatory pathways in TBI, which corroborates the ever increasing evidence regarding health-related outcomes with respect to a physically active lifestyle.

Exercise and Conjugated Linoleic Acid Supplementation Induce Changes in the Composition of Liver Fatty Acids

“…n-6 PUFAs are precursors of many proinflammatory molecules (Mika and Sledzinski, 2017). Physical exercise is known to attenuate inflammation and oxidative stress in the liver (de Castro et al, 2017). However, the inflammatory response may be triggered by many various factors, and the elevated content of n-6 PUFAs might not be enough to induce inflammation in liver tissues.…”

Serum Amyloid A Protein as a Potential Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

“…This peripheric inflammation mediated by cytokines and other small molecules promotes transmigration of leukocytes and an increase in systemic inflammation and damage in peripheral organs [17], including the liver. A recent study has shown how a single fluid percussion injury (FPI) episode in the rat cortex induces significant peripheral inflammatory and oxidative stress, disrupt redox statutes, and mitochondrial function in the liver [18]. High levels of circulating cytokines elicited by brain trauma affect the response injury in the brain and contribute to a blood-brain barrier opening and neutrophil infiltration [19].…”

The role of neutrophil granulocytes in immune-to-brain communication

“…Underlying mechanism of exercise on immune cell trafficking involve changes in adhesion molecules [90] and chemokine receptor expression [91]. As a result, previous exercise reduced neutrophil infiltration to the injury side were accompanied by attenuated secondary damage in a model of severe traumatic brain injury [92].…”