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.

KEY POINTS: An early inflammatory response and oxidative stress are implicated in the signal transduction that alters both hepatic redox status and mitochondrial function after traumatic brain injury (TBI). Peripheral oxidative/inflammatory responses contribute to neuronal dysfunction after TBI Exercise training alters the profile of oxidative-inflammatory status in liver and protects against acute hyperglycaemia and a cerebral inflammatory response after TBI. Approaches such as exercise training, which attenuates neuronal damage after TBI, may have therapeutic potential through modulation of responses by metabolic organs. The vulnerability of the body to oxidative/inflammatory in TBI is significantly enhanced in sedentary compared to physically active counterparts. 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.

Swimming training prevents alterations in acetylcholinesterase and butyrylcholinesterase activities in hypertensive rats.

BACKGROUND: Cholinergic enzyme activities are altered in hypertension, reflecting a low-grade inflammation. Regular physical exercise exerts anti-inflammatory effects and has been described as a coadjutant in the treatment of hypertension. In this study, we investigated the effect of 6 weeks of swimming training on cholinergic enzyme activities (acetylcholinesterase and butyrylcholinesterase) in Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. METHODS: The rats were divided into 4 groups: control (n = 10), exercise (n = 10), L-NAME (n = 10), and exercise L-NAME (n = 10). The animals were trained 5 times per week in an adapted swimming system for 60 minutes with a gradual increase of the workload up to 5% of animal's body weight. Enzyme activities were measured spectrophotometrically in lymphocytes, whole blood, and serum. RESULTS: A significant rise in acetylcholinesterase activity was observed in lymphocytes and whole blood as well as in serum butyrylcholinesterase activity in the L-NAME group when compared with the other groups (P < 0.05), and the increase in cholinesterase activities was positively correlated with the rise in blood pressure (r = 0.5721, r = 0.6121, and r = 0.5811, respectively). Swimming training was efficient in preventing these alterations in the exercise L-NAME group, which displayed values similar to those of the control group. Exercise training demonstrated a significant hypotensive effect in hypertensive rats. CONCLUSIONS: Exercise training was shown to prevent increased cholinesterase related to inflammatory processes in hypertensive rats, providing a new insight about protective exercise mechanisms to avoid hypertension-related inflammation.

Treadmill exercise protects against pentylenetetrazol-induced seizures and oxidative stress after traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of acquired epilepsy, and significant resources are required to develop a better understanding of the pathologic mechanism as targets for potential therapies. Thus, we decided to investigate whether physical exercise after fluid percussion injury (FPI) protects from oxidative and neurochemical alterations as well as from behavioral electroencephalographic (EEG) seizures induced by subeffective convulsive doses of pentylenetetrazol (PTZ; 35 mg/kg). Behavioral and EEG recordings revealed that treadmill physical training increased latency to first clonic and tonic-clonic seizures, attenuated the duration of generalized seizures, and protected against the increase of PTZ-induced Racine scale 5 weeks after neuronal injury. EEG recordings also revealed that physical exercise prevented PTZ-induced amplitude increase in TBI animals. Neurochemical analysis showed that exercise training increased glutathione/oxidized glutathione ratio and glutathione levels per se. Exercise training was also effective against alterations in the redox status, herein characterized by lipid peroxidation (thiobarbituric acid reactive substances), protein carbonyl increase, as well as the inhibition of superoxide dismutase and Na⁺,K⁺-ATPase activities after FPI. On the other hand, histologic analysis with hematoxylin and eosin revealed that FPI induced moderate neuronal damage in cerebral cortex 4 weeks after injury and that physical exercise did not protect against neuronal injury. These data suggest that the ability of physical exercise to reduce FPI-induced seizures is not related to its protection against neuronal damage; however, the effective protection of selected targets, such as Na⁺/K⁺-ATPase elicited by physical exercise, may represent a new line of treatment for post-traumatic seizure susceptibility.

Physical training prevents oxidative stress in L-NAME-induced hypertension rats.

The present study investigated the effects of a 6-week swimming training on blood pressure, nitric oxide (NO) levels and oxidative stress parameters such as protein and lipid oxidation, antioxidant enzyme activity and endogenous non-enzymatic antioxidant content in kidney and circulating fluids, as well as on serum biochemical parameters (cholesterol, triglycerides, urea and creatinine) from Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension treated rats. Animals were divided into four groups (n = 10): Control, Exercise, L-NAME and Exercise L-NAME. Results showed that exercise prevented a decrease in NO levels in hypertensive rats (P < 0·05). An increase in protein and lipid oxidation observed in the L-NAME-treated group was reverted by physical training in serum from the Exercise L-NAME group (P < 0·05). A decrease in the catalase (CAT) and superoxide dismutase (SOD) activities in the L-NAME group was observed when compared with normotensive groups (P < 0·05). In kidney, exercise significantly augmented the CAT and SOD activities in the Exercise L-NAME group when compared with the L-NAME group (P < 0·05). There was a decrease in the non-protein thiols (NPSH) levels in the L-NAME-treated group when compared with the normotensive groups (P < 0·05). In the Exercise L-NAME group, there was an increase in NPSH levels when compared with the L-NAME group (P < 0·05). The elevation in serum cholesterol, triglycerides, urea and creatinine levels observed in the L-NAME group were reverted to levels close to normal by exercise in the Exercise L-NAME group (P < 0·05). Exercise training had hypotensive effect, reducing blood pressure in the Exercise L-NAME group (P < 0·05). These findings suggest that physical training could have a protector effect against oxidative damage and renal injury caused by hypertension.