Πέμπτη 20 Ιουλίου 2017

Previous physical exercise alters hepatic profile of oxidative-inflammatory status and limits the secondary brain damage induced by severe TBI 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. In this sense, we decided to investigate whether peripheral oxidative/inflammatory response contributes to the neuronal dysfunction after TBI as well as prophylactic role of exercise training. Animals were submitted to fluid percussion injury (FPI) after 6 weeks of swimming training. Previous exercise training increased mRNA expression of X receptor alpha (LXR-α), ATP-binding cassette transporter (ABCA1), and decreased inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (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 (NPSH and GSH decreases, and 2',7'-dichlorofluorescein diacetate oxidation and protein carbonyl increases) which altered hepatic redox status (myeloperoxidase and superoxide dismutase activities increase, and catalase activity inhibition) mitochondrial function (MTT, Δψ decrease and citrate synthase activity inhibition) and ion gradient homeostasis (Na+,K+-ATPase activity inhibition) when analysed 24 h after TBI. Previous exercise training also protected against the dysglycemia, impaired hepatic signalling (pJNK increase, pIRS and pAKT expression decrease) high levels of circulating and neuronal cytokines, opening of BBB, neutrophils infiltration and Na+,K+-ATPase activity inhibition in ipsilateral cortex after TBI. Moreover, the impairment of protein function, neurobehavioral (neuromotor dysfunction and spatial learning) disability and hippocampal cell damage in sedentary rats suggest exercise training also modulates peripheral oxidative/inflammatory pathways in TBI, which corroborates the ever increasing evidence on health-related outcomes of a physically active lifestyle.

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