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With 4 billion people in lockdown in the world, COVID-19 outbreak may result in excessive sedentary time, especially in the population of vulnerable and disabled subjects. In many chronic disorders and diseases including type 2 diabetes mellitus and hypertension, cardiovascular and immune beneficial effects of exercise interventions should be reminded.

Cervical spinal cord injury (SCI) results in permanent life-altering motor and respiratory deficits. Other than mechanical ventilation for respiratory insufficiency secondary to cervical SCI, effective treatments are lacking and the development of animal models to explore new therapeutic strategies are needed. The aim of this work was to demonstrate the feasibility of using a mouse model of partial cervical spinal hemisection at the second cervical metameric segment (C2) to investigate the impact of 6 weeks training on forced exercise wheel system on locomotor/respiratory plasticity muscles. To measure run capacity locomotor and respiratory functions, incremental exercise tests and diaphragmatic electromyography were done. In addition, muscle fiber type composition and capillary distribution were assessed at 51 days following chronic C2 injury in diaphragm, extensor digitorum communis (EDC), tibialis anterior (TA) and soleus (SOL) muscles. Six-week exercise training increased the running capacity of trained SCI mice. Fiber type composition in EDC, TA and SOL muscles was not modified by our protocol of exercise. The vascularization was increased in all muscle limbs in SCI trained group. No increase in diaphragmatic electromyography amplitude of the diaphragm muscle on the side of SCI was observed, while the contraction duration was significantly decreased in sedentary group compared to trained group. Cross-sectional area of type IIa myofiber in the contralateral diaphragm side of SCI was smaller in trained group. Fiber type distribution between contralateral and ipsilateral diaphragm in SCI sedentary group was affected, while no difference was observed in trained group. In addition, the vascularization of the diaphragm side contralateral to SCI was increased in trained group. All these results suggest an increase in fatigue resistance and a contribution to the running capacity in SCI trained group. Our exercise protocol could be a promising non-invasive strategy to sustain locomotor and respiratory muscle plasticity following SCI.

Dexamethasone (DEX) causes rarefaction. In contrast, training (T) prevents rarefaction and stimulates angiogenesis. This study investigated the mechanisms responsible for the preventive role of T in DEX-induced rarefaction. Rats underwent T or were kept sedentary (8 weeks) and were treated with DEX or saline during the following 14 days. Tibialis anterior muscle was used for measurements of capillary density (CD), capillary-to-fiber ratio (C:F ratio), superoxide dismutase CuZn (SOD-1), superoxide dismutase MnSOD (SOD-2), catalase (CAT) mRNA as well as SOD-1, SOD-2, CAT, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGF-R2), cyclooxygenase-2 (COX-2), B-cell lymphoma 2 (Bcl-2), Bd-2-like protein 4 (Bax), p-Bax, and caspase-3 cleaved protein levels. DEX decreased CD (-38.1%), C:F ratio (-30.0%), VEGF (-19.0%), VEGFR-2 (-20.1%), COX-2 (-22.8%), Bcl-2 (-20.5%), Bcl-2/Bax ratio (-13.7%), p-Bax/Bax (-20.0%) and increased SOD-2 (+41.6%) and caspase-3 cleaved (+24.1%). Conversely, T prevented reductions in CD (+54.2%), C:F ratio (+32.9%), VEGF (+25.3%), VEGFR-2 (+22.2%), COX-2 (+31.5%), Bcl-2 (+35.5%), Bcl-2/Bax ratio (+19.9%), p-Bax/Bax (+32.1%), and caspase-3 cleaved increase (-7.8%). T increased CAT mRNA (+21.5%) in the DEX-treated group. In conclusion, T prevented the DEX-induced rarefaction by increasing antioxidant enzymes resulting in a better balance between apoptotic and anti-apoptotic protein levels.

Made available in DSpace on 2020-12-12T02:23:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-04-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) This work investigated the mechanisms induced by exercise training that may contribute to attenuate dexamethasone (DEX)-induced microvascular rarefaction and hypertension. Wistar rats underwent training protocol or were kept sedentary for 8 weeks. Dexamethasone was administered during the following 14-days and hemodynamic parameters were recorded at the end. Capillary density (CD) and capillary-to-fiber ratio (C:F ratio) were obtained in soleus muscle (SOL). Also, vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), endothelial nitric oxide synthase (eNOS), B-cell lymphoma 2 (Bcl-2), Bcl-2-like protein 4 (Bax), p-BAX and caspase-3 cleaved protein levels were analyzed. DEX treatment significantly increased blood pressure (+14%), which was associated with reduced C:F ratio (−41.0%) and CD (−43.1%). Reduction of vessel density was associated with decreased VEGF (−15.6%), VEGFR-2 (−14.6%), Bcl-2 (−18.4%), Bcl-2/Bax ratio (−29.0%) and p-Bax/Bax (−25.4%), and also with increased caspase-3 cleaved protein level (25%). Training, on the other hand, prevented microvessels loss by mitigating all proteins changes induced by DEX. In addition, angiogenic and apoptotic proteins were significantly correlated with CD, which, in turn, was associated with blood pressure. Therefore, we may point out that exercise training is a good strategy to attenuate DEX-induced microvascular rarefaction in soleus muscle and this response involves a better balance between apoptotic and angiogenic proteins, which may contribute for the attenuation of hypertension. Department of Physical Education – São Paulo State University (UNESP) Science Faculty, Av. Eng. Luiz Edmundo Carrijo Coube, 14-01 – Vargem Limpa Joint Graduate Program in Physiological Sciences PIPGCF UFSCar/UNESP, Rodovia Washington Luiz, km 235 Monjolinho, 676 Department of Biological Sciences Bauru School of Dentistry University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75 Department of Physical Education – São Paulo State University (UNESP) Science Faculty, Av. Eng. Luiz Edmundo Carrijo Coube, 14-01 – Vargem Limpa Joint Graduate Program in Physiological Sciences PIPGCF UFSCar/UNESP, Rodovia Washington Luiz, km 235 Monjolinho, 676

International audience; High spinal cord injuries (SCI) lead to permanent respiratory insufficiency, and the search for new therapeutics to restore this function is essential. To date, the most documented preclinical model for high SCI is the rat cervical C2 hemisection. However, molecular studies with this SCI model are limited due to the poor availability of genetically modified specimens. The aim of this work was to evaluate the pathophysiology of respiratory activity following a cervical C2 injury at different times post-injury in a C57BL/6 mouse model. No significant spontaneous recovery of diaphragmatic activity was observed up to 30 days post-injury in eupneic condition. However, during a respiratory challenge, i.e. mild asphyxia, a partial restoration of the injured diaphragm was observed at 7 days post-injury, corresponding to the crossed phrenic phenomenon. Interestingly, the diaphragmatic recording between 2 respiratory bursts on the injured side showed an amplitude increase between 1–7 days post-injury, reflecting a change in phrenic motoneuronal excitability. This increase in inter-burst excitability returned to pre-injured values when the crossed phrenic phenomenon started to be effective at 7 days post-injury. Taken together, these results demonstrate the ability of the mouse respiratory system to express long-lasting plasticity following a C2 cervical hemisection and genetically modified animals can be used to study the pathophysiological effects on these plasticity phenomena.

Objective Although aerobic exercise training has been recommended as nonpharmacological treatment of high blood pressure, the mechanisms of training-induced blood pressure lowering effects in dexamethasone (DEX)-induced hypertension remain unclear. Therefore, the aim of this study was to investigate the preventive role of exercise training in counteracting DEX-induced hypertension. Methods Rats were submitted to aerobic exercise training for 8 weeks or kept sedentary and then treated with DEX (50 μg/kg/day, s.c.) or saline injections for 14 days. Thereafter, all rats underwent carotid artery catheterization, and cardiovascular autonomic modulation was evaluated by spectral analysis. In addition, soleus muscle was collected for morphometric and protein level analysis. Results DEX treatment increased arterial pressure concomitantly with an increase in low-frequency spectral power of systolic arterial pressure and low frequency in pulse interval (94.11 and 58.58%, respectively), and a decrease in high-frequency spectral power of pulse interval (-12.05%). Capillary density (-25.87%), capillary-to-fibers ratio (-21.22%), vascular endothelial growth factor level (-15.10%), B-cell lymphoma 2 (Bcl-2) level (-16.40%) and Bcl-2/Bcl-2 associated X protein ratio (-27.14%) were all decreased after DEX treatment. Exercise training attenuated DEX-induced increase in arterial pressure accompanied by an attenuation of low-frequency spectral power of systolic arterial pressure, low frequency in pulse interval increases and high-frequency spectral power of pulse interval decrease. Training also prevented the decrease in capillary density (+44.43%), capillary-to-fibers ratio (+36.97%), vascular endothelial growth factor (+16.46%), Bcl-2 (+15.21%) protein level and Bcl-2/Bcl-2-associated X protein ratio (+30.93%). Conclusion These results demonstrate that exercise training improves cardiovascular autonomic balance to the heart associated with an improvement in sympathetic modulation of vascular tone and microcirculatory function in the skeletal muscle of DEX-induced hypertensive rats.