Relative Gastrocnemius Research Articles

Probiotics Attenuate Myopathic Changes in Aging Rats via Activation of the Myogenic Stellate Cells.

Aging represents a complex biological process associated with decline in skeletal muscle functions. Aging impairs satellite cells that serve as muscle progenitor cells. Probiotic supplementation may have many beneficial effects via various mechanisms. We examined the possible effects of probiotics in stimulating the proliferation of myogenic stellate cells in aging rats. Twenty-four male albino Sprague-Dawley rats were classified equally into four groups: adult control, old control, adult + probiotics, and old + probiotics. Probiotics (Lactobacillus LB) were administered gavage at a dose of 1ml (1 × 109CFU/ml/day) for 4 weeks. A significant increase in the relative gastrocnemius weight ratio and improvement of contractile parameters was detected in the old + probiotics group (0.6 ± 0.01) compared to the old control group (0.47 ± 0.01; P < 0.001). Probiotics significantly upregulated the activities of GSH, while NO and MDA were markedly decreased compared to control groups (P ≤ 0.001). Also, probiotics increased the mRNA and protein expressions of myogenin and CD34 (P < 0.05) as determined by real-time PCR and immunohistochemistry. Moreover, the old + probiotics group showed apparent restoration of the connective tissue spaces, reflecting the all-beneficial effects of probiotics. Our findings indicated that probiotics attenuated myopathic changes in aging rats probably through activation of the myogenic stellate cells. Probiotics improved the muscle weight, function, antioxidant activity, and myogenic transcription factors of the skeletal muscle.

Effects of Obesity in Old Age on the Basement Membrane of Skeletal Muscle in Mice.

Obesity and aging are known to affect the skeletal muscles. Obesity in old age may result in a poor basement membrane (BM) construction response, which serves to protect the skeletal muscle, thus making the skeletal muscle more vulnerable. In this study, older and young male C57BL/6J mice were divided into two groups, each fed a high-fat or regular diet for eight weeks. A high-fat diet decreased the relative gastrocnemius muscle weight in both age groups, and obesity and aging individually result in a decline in muscle function. Immunoreactivity of collagen IV, the main component of BM, BM width, and BM-synthetic factor expression in young mice on a high-fat diet were higher than that in young mice on a regular diet, whereas such changes were minimal in obese older mice. Furthermore, the number of central nuclei fibers in obese older mice was higher than in old mice fed a regular diet and young mice fed a high-fat diet. These results suggest that obesity at a young age promotes skeletal muscle BM formation in response to weight gain. In contrast, this response is less pronounced in old age, suggesting that obesity in old age may lead to muscle fragility.

An Effective Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Improves Sarcopenic Obesity in Obese Mice by Modulating Skeletal Muscle Metabolism.

PurposeThis study aimed to investigate the effect of Semaglutide on skeletal muscle and its metabolomics.MethodsA total of 18 male C57BL/6 mice were randomly divided into normal control (NC) group, high-fat diet (HFD) group and HFD+Semaglutide group, and were given standard diet, HFD diet, HFD diet plus Semaglutide, respectively. The body weight, gastrocnemius weight, serum lipid, blood glucose and inflammatory index levels of mice in each group were observed and compared, and the morphological and structural changes of gastrocnemius were also analyzed. Meanwhile, gastrocnemius metabolite changes were analyzed by untargeted metabolomics.ResultsAfter Semaglutide treatment, the food intake and body weight of mice were evidently decreased, while the relative gastrocnemius weight ratio were conversely increased. Meanwhile, the levels of TG, CHO, LDL, HDL, TNF-α, IL-6, IL-1β and HOMA-IR were all observed to decrease remarkably after Semaglutide intervention. Histological analysis showed that Semaglutide significantly improved the pathological changes of gastrocnemius, manifested as increased type I/type II muscle fiber ratio, total muscle fiber area, muscle fiber density, sarcomere length, mitochondrial number and mitochondrial area. Furthermore, metabolic changes of gastrocnemius after Semaglutide intervention were analyzed, and 141 kinds of differential metabolites were screened out, mainly embodied in lipids and organic acids, and enriched in 9 metabolic pathways including a variety of amino acids.ConclusionSemaglutide can significantly reduce the body weight and the accumulation of intramuscular fat, promote muscle protein synthesis, increase the relative proportion of skeletal muscle, and improve muscle function of obese mice, possibly by altering the metabolism of muscle lipids and organic acids.

MO414: Sucroferric Oxyhydroxide (Velphoro®) Treatment Mitigates the Signs of Ageing-Related Sarcopaenia in Old Mice

Abstract BACKGROUND AND AIMS Sarcopaenia, defined as the loss of muscle mass and function, is an ageing-related pathology associated with some important diseases such as chronic kidney disease (CKD). Hyperphosphatemia has been associated with both, ageing and CKD. Old mice show an increase in serum phosphate concentration and a reduction in muscle mass, forelimb strength, gait speed and transition time in the static bar, with respect to young mice. Previous results of our group showed the beneficial effects of a low phosphate diet on ageing-related sarcopaenia. Given that the implementation of dietary phosphate restriction entails difficulties in the elderly, the aim of this work was to analyse the beneficial effects of a diet supplemented with a phosphate binder on the signs of sarcopaenia. METHOD C57BL6 male mice were used for in vivo studies: 5-month-old (young) and 24-month-old (old), which were fed with a powder standard diet (containing 0.6% of phosphate). Some old mice were fed with a hypophosphatemic diet (containing 0.2% of phosphate) or with a diet supplemented with 5% sucroferric oxyhydroxide (Velphoro®) for the last 3 months before sacrifice. Serum phosphate levels were analysed with a commercial kit. Muscle mass was estimated by measuring the gastrocnemius muscle mass divided by total body mass, muscle force was measured by a grip test and physical performance was evaluated by a gait test and the static bar test. RESULTS Velphoro® treated old mice showed a significant and more effective reduction in phosphate serum levels than old mice fed with the hypophosphatemic diet. No differences were observed in the relative gastrocnemius muscle mass between the three old mice experimental groups. By contrast, old mice fed with the standard diet supplemented with Velphoro® displayed an increased muscular strength and physical performance, improving the gait speed and reducing the transition time in the static bar, compared with old mice fed with the standard diet. Results obtained with Velphoro® treatment were similar to those observed in old mice fed with the hyphophosphatemic diet, but Velphoro® treatment achieve better results in motor coordination in the static bar test. CONCLUSION Dietary restriction of phosphate is a useful approach to mitigate the signs of ageing-related sarcopaenia (muscle strength and physical performance) in old mice. The use of Velphoro®, as a phosphate binder, exhibits similar or even better results than the hypophosphatemic diet. Therefore, the administration of Velphoro® could attenuate the signs of sarcopaenia in the elderly or in ageing-related diseases in which sarcopaenia is common, like CKD.

Three-Dimensional Microfilament Printing of a Decellularized Extracellular Matrix (dECM) Bioink Using a Microgel Printing Bath for Nerve Graft Fabrication and the Effectiveness of dECM Graft Combined with a Polycaprolactone Conduit.

Various synthetic and decellularized materials are being used to reconstruct peripheral nerve defects and replace autologous nerve grafts. In this study, we developed a microgel printing bath to three-dimensionally (3D) print a peripheral nervous system decellularized extracellular matrix nerve graft reinforced by a polycaprolactone (PCL) conduit. The straightforward fabrication method of an alginate microgel-supplemented printing bath allows a 30 μm filament resolution of a low viscous decellularized extracellular matrix hydrogel with neutral pH. When applied to a sciatic nerve defect model of rats, the total number of regenerated axons and relative gastrocnemius muscle weight ratio were comparable to those of the autologous nerve graft group. Meanwhile, the results were superior to those of the porcine decellularized nerve graft group or the 3D printed decellularized extracellular matrix graft group. This study will be the first step demonstrating that the 3D printed decellularized extracellular matrix (dECM) graft with a PCL conduit is an effective and reliable choice to replace an autologous nerve graft in the near future.

Sodium phenylbutyrate inhibits Schwann cell inflammation via HDAC and NF\u03baB to promote axonal regeneration and remyelination

BackgroundEpigenetic regulation by histone deacetylases (HDACs) in Schwann cells (SCs) after injury facilitates them to undergo de- and redifferentiation processes necessary to support various stages of nerve repair. Although de-differentiation activates the synthesis and secretion of inflammatory cytokines by SCs to initiate an immune response during nerve repair, changes in either the timing or duration of prolonged inflammation mediated by SCs can affect later processes associated with repair and regeneration. Limited studies have investigated the regulatory processes through which HDACs in SCs control inflammatory cytokines to provide a favorable environment for peripheral nerve regeneration.MethodsWe employed the HDAC inhibitor (HDACi) sodium phenylbutyrate (PBA) to address this question in an in vitro RT4 SC inflammation model and an in vivo sciatic nerve transection injury model to examine the effects of HDAC inhibition on the expression of pro-inflammatory cytokines. Furthermore, we assessed the outcomes of suppression of extended inflammation on the regenerative potential of nerves by assessing axonal regeneration, remyelination, and reinnervation.ResultsSignificant reductions in lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (tumor necrosis factor-α [TNFα]) expression and secretion were observed in vitro following PBA treatment. PBA treatment also affected the transient changes in nuclear factor κB (NFκB)-p65 phosphorylation and translocation in response to LPS induction in RT4 SCs. Similarly, PBA mediated long-term suppressive effects on HDAC3 expression and activity. PBA administration resulted in marked inhibition of pro-inflammatory cytokine secretion at the site of transection injury when compared with that in the hydrogel control group at 6-week post-injury. A conducive microenvironment for axonal regrowth and remyelination was generated by increasing expression levels of protein gene product 9.5 (PGP9.5) and myelin basic protein (MBP) in regenerating nerve tissues. PBA administration increased the relative gastrocnemius muscle weight percentage and maintained the intactness of muscle bundles when compared with those in the hydrogel control group.ConclusionsSuppressing the lengthened state of inflammation using PBA treatment favors axonal regrowth and remyelination following nerve transection injury. PBA treatment also regulates pro-inflammatory cytokine expression by inhibiting the transcriptional activation of NFκB-p65 and HDAC3 in SCs in vitro.

Obesity-induced alterations to the immunoproteasome: a potential link to intramuscular lipotoxicity.

Although the mechanisms are unclear, inflammation and/or lipotoxicity likely contribute to obese muscle pathology. The immunoproteasome is known to respond to inflammation and oxidative damage and may aid muscle regeneration. We sought to determine whether diet-induced obesity (DIO) influences the immunoproteasome subunits LMP7 and MECL-1 in mouse muscle with and without exercise-induced muscle damage (EIMD). Muscle mass, regeneration, macrophage content and lipid peroxidation (8-isoprostane) were also assessed. Sixty male, 4-week-old C57BL/6J mice were fed a high-fat (HFD) or low-fat diet for 12 weeks. Mice were then subdivided into EIMD or no muscle damage (NMD) groups. The gastrocnemius muscle was excised 1 or 5 days after EIMD, producing 6 groups (n = 10/group). Body mass was greater; however, relative gastrocnemius mass was lower in HFD-fed mice. Despite no macrophage or MECL-1 alterations, LMP7 and 8-isoprostane were increased in obese mice in the NMD and 1 day post-EIMD groups. However, 8-isoprostane was reduced in obese mice 5 days post-EIMD, and accompanied by increased muscle LMP7, MECL-1 and macrophage content. Consequently, DIO may impair the immunoproteasome's ability to control muscle lipid peroxidation but is reversed with eccentric exercise. Although muscle regeneration was unchanged, immunoproteasome dysregulation occurs in obese muscle and may contribute to muscle pathology. Novelty: DIO may impair the intramuscular immunoproteasome response to lipid peroxidation. Acute eccentric exercise may protect obese individuals from muscle lipotoxicity via immunoproteasome upregulation.

Protein Supplementation Enhances the Effects of Intermittent Loading on Skeletal Muscles by Activating the mTORC1 Signaling Pathway in a Rat Model of Disuse Atrophy.

Inactivity leads to skeletal muscle atrophy, whereas intermittent loading (IL) during hind limb unloading (HU) attenuates muscle atrophy. However, the combined effects of IL and protein supplementation on disuse muscle atrophy are unclear. Therefore, we investigated the effects of IL and a high-protein oral nutritional supplement (HP) during HU on skeletal muscle mass and protein synthesis/breakdown. Male F344 rats were assigned to the control (CON), 14-day HU (HU), IL during HU (HU + IL), and IL during HU followed by HP administration (2.6 g protein/kg/day; HU + IL + HP) groups. Soleus and gastrocnemius muscles were sampled 30 min after the last IL and HP supplementation. HU decreased relative soleus and gastrocnemius muscle masses. Relative muscle masses and p70 ribosomal protein S6 kinase/ribosomal protein S6 phosphorylation in soleus and gastrocnemius muscles were higher in the HU + IL group than the HU group and further higher in the HU + IL + HP group than the HU + IL group in gastrocnemius muscle. Therefore, protein administration plus IL effectively prevented skeletal muscle atrophy induced by disuse, potentially via enhanced activation of targets downstream of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.

Age-related changes in histone modification in rat gastrocnemius muscle.

Changes in histone acetylation and methylation status with aging affect gene expression and phenotype in several tissues; however, age-related changes in histone modification in the skeletal muscle have not been elucidated yet. This study investigated age-related global changes in histone modification in rat gastrocnemius muscle. Male Wistar rats (n = 28) were assigned to one of four age groups (n = 7 per group) corresponding to different life stages: 3 months old (3-mo; young), 6 months old (adult), 12 months old (12-mo; middle-aged), and 24 months old (24-mo; old). The gastrocnemius muscle was removed and global histone modification (acetylation and tri-methylation) at K9 and K27 was evaluated by western blotting. Relative muscle mass decreased in the 12- and 24-mo rats accompanied with reduction in type IIb myosin heavy chain isoforms and Myh4 (MHC IIB) mRNA expression. Histone H3 acetylation decreased in an age-dependent manner, with lower levels in 12- and 24-mo groups than in the 3-mo group. K9 and K27 acetylation decreased with age. Although there was no significant change in K27 tri-methylation, K9 tri-methylation showed an age-dependent decline. Histone modification status (acetylation at K9 and K27 and tri-methylation at K9) was positively associated with relative gastrocnemius muscle weight, the percentage of type IIb myosin heavy chain isoform, myosin heavy chain type IIb protein expression, and the level of Myh4 mRNA. Thus, global histone H3 methylation and acetylation decrease with age, and the latter might be associated with age-related muscle atrophy of rat gastrocnemius muscle.

Adipose-Derived Neural Stem Cells Combined with Acellular Dermal Matrix as a Neural Conduit Enhances Peripheral Nerve Repair

Reconstruction to close a peripheral nerve gap continues to be a challenge for clinical medicine, and much effort is being made to develop nerve conduits facilitate nerve gap closure. Acellular dermal matrix (ADM) is mainly used to aid wound healing, but its malleability and plasticity potentially enable it to be used in the treatment of nerve gaps. Adipose-derived stem cells (ADSCs) can be differentiated into three germ layer cells, including neurospheres. We tested the ability of ADSC-derived neural stem cells (NSCs) in combination with ADM or acellular sciatic nerve (ASN) to repair a transected sciatic nerve. We found that NSCs form neurospheres that express Nestin and Sox2, and could be co-cultured with ADM in vitro, where they express the survival marker Ki67. Following sciatic nerve transection in rats, treatment with ADM+NSC or ASN+NSC led to increases in relative gastrocnemius weight, cross-sectional muscle fiber area, and sciatic functional index as compared with untreated rats or rats treated with ADM or ASN alone. These findings suggest that ADM combined with NSCs can improve peripheral nerve gap repair after nerve transection and may also be useful for treating other types of neurological gaps.

Abstract 88: Local Delivery of FK506 to a Mouse Sciatic Nerve Injury Increases Nerve Regeneration Outcomes

PURPOSE: In the clinic, there are limited treatment strategies for the repair of peripheral nerve injuries, and the majority of off-the-shelf nerve repair devices lack added functionality. Direct repair is among the most commonly performed nerve repair procedures and presently there is no clinical therapeutic available that improves outcomes after direct repair. The objective of this study is to assess the efficacy of local, controlled delivery of FK506 to improve nerve regeneration outcomes in the setting of nerve transection injury and repair. METHODS: Solvent casting techniques were used to embed FK506 into poly(lactide-co-caprolactone) (PLC) films for the creation of a nerve wrap – drug delivery system that is capable of an extended, localized release of FK506 to injured nerves. In vitro drug rate of release testing and drug bioactivity assays were performed to determine the FK506 release profile and to verify release FK506 bioactivity. A mouse sciatic transection and direct-suture repair model was used to evaluate the effect local, controlled FK506 delivery could have on nerve regeneration outcomes greater than direct-suture repair alone. Animals were sacrificed at 6 weeks for electrophysiological assessment, determination of gastrocnemius muscle mass recovery, and sciatic nerve histological evaluation. RESULTS: A linear release (R2=0.991) of FK506 for 30+ days was observed for two FK506 loading concentrations (0.01 % and 0.05% w/w of FK506/PLC). The released FK506 matched control FK506 levels of neurite extension in the dorsal root ganglion assay. Relative gastrocnemius muscle weight, relative foot EMG, and total number of axons distal of the repair site were significantly greater in mice treated with the 0.01% FK506 nerve wrap than the non-drug groups. For the 0.05% nerve wraps, the total axon count distal to the repair site was found to be significantly greater, but no significant differences were observed for the other metrics. CONCLUSION: Results of this study indicate that extended, localized delivery of FK506 to a mouse sciatic transection and direct repair can improve nerve regeneration outcomes in a sciatic nerve transection and repair model. A dose-dependent response in the nerve regeneration metrics was observed, indicating there is an optimal dose range for local delivery of FK506.

Cross talk between androgen and Wnt signaling potentially contributes to age-related skeletal muscle atrophy in rats.

We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum-free and total testosterone (TEST) and gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3, 6, 12, 18, and 24 mo (mo) old ( n = 9 per group). Free and total TEST was greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass ( r = 0.395, P = 0.007) as well as AR and Wnt5 protein levels (r = 0.670, P < 0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating C2C12-derived myotubes with lower (75 ng/ml) and higher (150 ng/ml) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size ( P < 0.05) suggesting this ligand may affect muscle fiber size in vivo. We next tested if Wnt5a protein levels were androgen-modulated by examining 10-mo-old male Fischer 344 rats ( n = 10-11 per group) that were orchiectomized and treated with testosterone-enanthate (TEST-E); trenbolone enanthate (TREN), a nonaromatizable synthetic testosterone analogue; or a vehicle (ORX only) for 4 wk. Interestingly, TEST-E and TREN treatments increased Wnt5a protein in the androgen-sensitive levator ani/bulbocavernosus muscle compared with ORX only ( P < 0.05). To summarize, aromatizable and nonaromatizable androgens increase Wnt5a protein expression in skeletal muscle, age-related decrements in muscle AR may contribute Wnt5a protein decrements, and our in vitro data imply this mechanism may contribute to age-related muscle loss. NEW & NOTEWORTHY Results from this study demonstrate androgen and Wnt5 protein expression decrease with aging, and this may be a mechanism involved with age-related muscle loss.

The Relationship Between Serum Testosterone And Skeletal Muscle Wnt Signaling Markers In 3-24-month Old Rats

PURPOSE: We sought to determine if canonical Wnt signaling markers are related to serum testosterone concentrations and muscle weights in rodents. METHODS: Male Fischer 344 rats (300-600g) were aged 3, 6, 12, 18 and 24 months, euthanized, gastrocnemius muscle was extracted and wet skeletal muscle weights were obtained. Muscle tissue was then processed for analysis via western blotting. Additionally, serum was obtained and assays were performed for total and free testosterone (TEST). RESULTS: Relative (body mass-adjusted) gastrocnemius masses revealed significant between-group differences (p<0.001) and were greater at 3 and 6 versus 12, 18 and 24 months (p<0.05). Serum free TEST was 102% greater at 6 versus 3 (p<0.05), 165% greater at 6 versus 12 (p<0.05), 101% greater at 6 versus 18 (p<0.05), and 95% greater at 6 versus 24 months (p<0.05).Total TEST was 305% greater at 6 versus 12 (p<0.05), 273% greater at 6 versus 18 (p<0.05), and 185% greater at 6 versus 24 months (p<0.05). Wnt5a/b was 26% greater at 3 versus 12 (p<0.05), and 54% at 3 versus 24 months (p<0.05). Additionally, Wnt5a/b was 26% greater at 6 versus 12 (p<0.05), and 54% at 6 versus greater than 24 months (p<0.05). Relative gastrocnemius masses and Wnt5a/b exhibited a moderate positive correlation r=0.397, (p=0.007). Beta-catenin was greater at 6 versus 3 and 18 months (p<0.05). Additionally, beta-catenin was greater at 12 versus 3 and 18 months (p<0.05), and 24 versus 3 and 18 months (p<0.05). Androgen receptor (AR) was greater at 3 versus 18 and 24 months (p<0.05), greater at 6 versus 18 and 24 months, and greater at 12 versus 18 and 24 months (p<0.05). Furthermore, AR had a moderate positive correlation r=0.438, (p=0.003) with relative gastrocnemius masses. Additionally, AR had a strong positive relationship correlation r=0.670, (p<0.001) with Wnt5a/b. CONCLUSIONS: It appears that intramuscular Wnt signaling proteins, androgen receptor content, serum testosterone, and gastrocnemius masses are inter-related, and decline with aging. Androgen-sensitive mechanisms related to Wnt signaling should be further investigated in skeletal muscle in order to ascertain if these processes contribute to sacropenia.

Progressive resistance-loaded voluntary wheel running increases hypertrophy and differentially affects muscle protein synthesis, ribosome biogenesis, and proteolytic markers in rat muscle.

We examined if 6weeks of progressive resistance-loaded voluntary wheel running in rats induced plantaris, soleus, and/or gastrocnemius hypertrophy and/or affected markers of translational efficiency, ribosome biogenesis, and markers of proteolysis. For 6weeks, 8 male Sprague-Dawley rats (~9-10weeks of age, ~300-325g) rats were assigned to the progressive resistance-loaded voluntary wheel running model (EX), and ten rats were not trained (SED). For EX rats, the wheel-loading paradigm was as follows - days 1-7: free-wheel resistance, days 8-15: wheel resistance set to 20%-25% body mass, days 16-24: 40% body mass, days 25-32: 60% body mass, days 33-42: 40% body mass. Following the intervention, muscles were analysed for markers of translational efficiency, ribosome biogenesis, and muscle proteolysis. Raw gastrocnemius mass (+13%, p<.01), relative (body mass-corrected) gastrocnemius mass (+16%, p<.001), raw plantaris mass (+13%, p<.05), and relative plantaris mass (+15%, p<.01) were greater in EX vs. SED rats. In spite of gastrocnemius hypertrophy, EX animals presented a 54% decrease in basal muscle protein synthesis levels (p<.01), a 125% increase in pan 4EBP1 levels (p<.001) and a 31% decrease in pan eIF4E levels (p<.05). However, in relation to SED animals, EX animals presented a 70% increase in gastrocnemius c-Myc protein levels (p<.05). Most markers of translational efficiency and ribosome biogenesis were not altered in the plantaris or soleus muscles of EX vs. SED animals. Gastrocnemius F-box protein 32 and poly-ubiquinated protein levels were approximately 150% and 200% greater in SED vs. EX rats (p<.001). These data suggest that the employed resistance training model increases hind limb muscle hypertrophy, and this may be mainly facilitated through reductions in skeletal muscle proteolysis, rather than alterations in ribosome biogenesis or translational efficiency.

Voluntary Running Aids to Maintain High Body Temperature in Rats Bred for High Aerobic Capacity.

The production of heat, i.e., thermogenesis, is a significant component of the metabolic rate, which in turn affects weight gain and health. Thermogenesis is linked to physical activity (PA) level. However, it is not known whether intrinsic exercise capacity, aging, and long-term voluntary running affect core body temperature. Here we use rat models selectively bred to differ in maximal treadmill endurance running capacity (Low capacity runners, LCR and High capacity Runners, HCR), that as adults are divergent for aerobic exercise capacity, aging, and metabolic disease risk to study the connection between PA and body temperature. Ten high capacity runner (HCR) and ten low capacity runner (LCR) female rats were studied between 9 and 21 months of age. Rectal body temperature of HCR and LCR rats was measured before and after 1-year voluntary running/control intervention to explore the effects of aging and PA. Also, we determined whether injected glucose and spontaneous activity affect the body temperature differently between LCR and HCR rats at 9 vs. 21 months of age. HCRs had on average 1.3°C higher body temperature than LCRs (p < 0.001). Aging decreased the body temperature level of HCRs to similar levels with LCRs. The opportunity to run voluntarily had a significant impact on the body temperature of HCRs (p < 0.001) allowing them to maintain body temperature at a similar level as when at younger age. Compared to LCRs, HCRs were spontaneously more active, had higher relative gastrocnemius muscle mass and higher UCP2, PGC-1α, cyt c, and OXPHOS levels in the skeletal muscle (p < 0.050). These results suggest that higher PA level together with greater relative muscle mass and higher mitochondrial content/function contribute to the accumulation of heat in the HCRs. Interestingly, neither aging nor voluntary training had a significant impact on core body temperature of LCRs. However, glucose injection resulted in a lowering of the body temperature of LCRs (p < 0.050), but not that of HCRs. In conclusion, rats born with high intrinsic capacity for aerobic exercise and better health have higher body temperature compared to rats born with low exercise capacity and disease risk. Voluntary running allowed HCRs to maintain high body temperature during aging, which suggests that high PA level was crucial in maintaining the high body temperature of HCRs.

Effects of spinal cord injury-induced changes in muscle activation on foot drag in a computational rat ankle model.

Spinal cord injury (SCI) can lead to changes in muscle activation patterns and atrophy of affected muscles. Moderate levels of SCI are typically associated with foot drag during the swing phase of locomotion. Foot drag is often used to assess locomotor recovery, but the causes remain unclear. We hypothesized that foot drag results from inappropriate muscle coordination preventing flexion at the stance-to-swing transition. To test this hypothesis and to assess the relative contributions of neural and muscular changes on foot drag, we developed a two-dimensional, one degree of freedom ankle musculoskeletal model with gastrocnemius and tibialis anterior muscles. Anatomical data collected from sham-injured and incomplete SCI (iSCI) female Long-Evans rats as well as physiological data from the literature were used to implement an open-loop muscle dynamics model. Muscle insertion point motion was calculated with imposed ankle trajectories from kinematic analysis of treadmill walking in sham-injured and iSCI animals. Relative gastrocnemius deactivation and tibialis anterior activation onset times were varied within physiologically relevant ranges based on simplified locomotor electromyogram profiles. No-atrophy and moderate muscle atrophy as well as normal and injured muscle activation profiles were also simulated. Positive moments coinciding with the transition from stance to swing phase were defined as foot swing and negative moments as foot drag. Whereas decreases in activation delay caused by delayed gastrocnemius deactivation promote foot drag, all other changes associated with iSCI facilitate foot swing. Our results suggest that even small changes in the ability to precisely deactivate the gastrocnemius could result in foot drag after iSCI.

Omental pedicle transposition and suture repair of peripheral nerve: A comparative study of functional, histological, morphometric and relative gastrocnemius muscle weight in rabbits

The peripheral nervous system is able to regenerate after injury. Etiologies of injuries include penetrating injury, crush, traction, and ischemia compression. However, the presence of various nerve injury treatments such as coaptation and another technique to attain functional nerve regeneration are still inadequate. This study aimed to compare the effectiveness of omental pedicle transposition and epineural nerve suture on peripheral nerve regeneration in a rabbit model. Ten male New Zealand white rabbits were divided into two groups. In the primary epineural repair group or control group (CG), the left sciatic nerve was skeletonized from the sciatic notch till the point of bifurcation. The nerve was transected at the mid shaft of the femoral bone and repaired with six epineural sutures. In the treatment group (TG), the epineural repaired sciatic nerve was wrapped with omental pedicle around the site of coaptation. Assessment of the nerve regeneration was based on functional (motor and sensory), histological, morphometric criteria and relative gastrocnemius muscle weight. The results of the examination show that the treated group had better regeneration and functional recovery. Key words: Omental pedicle, regeneration, hispathological, morphometric, sciatic nerve.

English

The peripheral nervous system has the ability to regenerate after injury. Peripheral nerve injuries are caused by penetrating injury, crush, traction and ischemia compression. However, the availability of various nerve coaptation and other techniques for the attainment of functional nerve regeneration is still inadequate. The objective of this study was to compare the effectiveness of bone marrow stromal cells (BMSCs) implantation and epineural nerve suture on peripheral nerve regeneration in a rabbit model. Ten male New Zealand white rabbits were divided into two groups. In the primary epineural repair group (control group), the left sciatic nerve was skeletonized from the sciatic notch to the point of bifurcation, with the nerve been transected at the mid-shaft of the femoral bone and repaired with six epineural sutures. In the treated group, the epineural repaired nerve was implanted with BMSCs in the proximal and distal segments of the transected sciatic nerve. Assessment of the nerve regeneration was based on functional (motor and sensory), histological and morphometric criteria, including the number of myelinated nerve fibers, nerve fiber diameter, axon diameter, myelin sheath thickness, g ratio and relative gastrocnemius muscle weight. The results of the examination showed that the treated group had the best regeneration and functional recovery. &nbsp; Keyword:&nbsp;Bone marrow stromal cells (BMSCs), histopathology, morphometric, peripheral nerve, regeneration.

Stump Rotation in a Nerve Autograft by 2 Factors

The aim of this study was to determine the influence of stump rotation (fascicular cross-connection) on nerve autograft functional recovery. Thirty rat sciatic nerves were transected and repaired by autograft. The rats were divided into 3 groups according to the number of stump rotations of the autograft: (1) plain graft (PG-g, with no change in fascicular orientation, no difference in diameter), (2) graft rotation (GR-g, with no change in fascicular orientation, and diameter difference between fascicles), (3) stump rotation (SR-g, with cross-connection and diameter difference between fascicles). Relative gastrocnemius muscle weight and nerve fiber count were examined as anatomic recovery indices, and autotomy score (ATS) and toe-out angle as functional recovery indices. The results showed that SR-g had a significantly low functional recovery compared with PG-g and GR-g. However, there was no difference found in the anatomic recovery. These findings suggest that the stump rotation in nerve autograft had no effect on neural regeneration and muscle reinnervation; however, it had a negative effect on functional recovery. Because GR-g was similar to PG-g rather than SR-g in functional recovery, the diameter difference between fascicles appears to have had little effect on the functional recovery. The results of this study suggest that a novel approach to ATS interpretation is needed. It is recommended that (1) ATS 2 be considered the onset of autotomy instead of ATS 1; and (2) the frequency of "ATS 2 and above" should be considered for the comparison of the autotomy rather than the mean ATS.

Differences between the effect of anisotropic and isotropic laminin and nerve growth factor presenting scaffolds on nerve regeneration across long peripheral nerve gaps

Anisotropic scaffolds of agarose hydrogels containing gradients of laminin-1 (LN-1) and nerve growth factor (NGF) molecules were used to promote sciatic nerve regeneration across a challenging 20 mm nerve gap in rats. Step and continuous gradient anisotropic scaffolds were fabricated and characterized, and regeneration was compared to that in isotropic scaffolds with uniform concentrations of LN-1 and NGF and sciatic nerve grafts harvested from syngenic rats. Polysulfone tubular guidance channels were used to present the agarose-based scaffolds to the nerve stumps. Four months after implantation, regenerating axons were observed in animals implanted with anisotropic scaffolds with gradients of both LN-1 and NGF molecules and nerve grafts, but not in animals with isotropic scaffold implants. Also, the scaffolds with gradients of either LN-1 or NGF, with the other component being uniformly distributed in the scaffold, did not elicit axonal regeneration. The total number of myelinated axons was similar for the anisotropic scaffold and the nerve graft conditions, with the anisotropic scaffolds having a higher density of axons than the nerve grafts. Axonal diameter distribution was similar for the anisotropic scaffolds and the nerve grafts. The nerve grafts and anisotropic scaffolds resulted in better functional outcome compared to isotropic scaffolds as measured by the relative gastrocnemius muscle weight (RGMW). Additionally the state of neuromuscular junctions as assessed by pre- and post-synaptic staining revealed that both the anisotropic scaffolds performed as well as nerve grafts.