Ceren Yarar-Fisher

Body mass index underestimates adiposity in women with spinal cord injury

To assess the relationship between body mass index (BMI) and adiposity as well as the influence of injury level on this relationship in 24 women with spinal cord injury (SCI) and 23 able‐bodied (AB) women with similar age, race, and BMI.

Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity

The mechanisms underlying poor glucose tolerance in persons with spinal cord injury (SCI), along with its improvement after several weeks of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) training, remain unclear, but presumably involve the affected skeletal musculature. We, therefore, investigated skeletal muscle signaling pathways associated with glucose transporter 4 (GLUT-4) translocation at rest and shortly after a single bout of NMES-RE in SCI (n = 12) vs. able-bodied (AB, n = 12) men. Subjects completed an oral glucose tolerance test during visit 1 and ≈90 NMES-RE isometric contractions of the quadriceps during visit 2. Muscle biopsies were collected before, and 10 and 60 min after, NMES-RE. We assessed transcript levels of GLUT-4 by quantitative PCR and protein levels of GLUT-4 and phosphorylated- and total AMP-activated protein kinase (AMPK)-α, CaMKII, Akt, and AS160 by immunoblotting. Impaired glucose tolerance in SCI was confirmed by higher (P < 0.05) plasma glucose concentrations than AB at all time points after glucose ingestion, despite equivalent insulin responses to the glucose load. GLUT-4 protein content was lower (P < 0.05) in SCI vs. AB at baseline. Main group effects revealed higher phosphorylation in SCI of AMPK-α, CaMKII, and Akt (P < 0.05), and Akt phosphorylation increased robustly (P < 0.05) following NMES-RE in SCI only. In SCI, low skeletal muscle GLUT-4 protein concentration may, in part, explain poor glucose tolerance, whereas heightened phosphorylation of relevant signaling proteins (AMPK-α, CaMKII) suggests a compensatory effort. Finally, it is encouraging to find (based on Akt) that SCI muscle remains both sensitive and responsive to mechanical loading (NMES-RE) even ≈22 yr after injury.

MECHANOSENSITIVITY MAY BE ENHANCED IN SKELETAL MUSCLES OF SPINAL CORD–INJURED VERSUS ABLE-BODIED MEN

We investigated the effects of an acute bout of neuromuscular electrical stimulation–induced resistance exercise (NMES‐RE) on intracellular signaling pathways involved in translation initiation and mechanical loading–induced muscle hypertrophy in spinal cord–injured (SCI) versus able‐bodied (AB) individuals. AB and SCI individuals completed 90 isometric knee extension contractions at 30% of maximum voluntary or evoked contraction, respectively. Muscle biopsies were collected before, and 10 and 60 min after NMES‐RE. Protein levels of α7‐ and β1‐integrin, phosphorylated and total GSK‐3α/β, S6K1, RPS6, 4EBP1, and FAK were assessed by immunoblotting. SCI muscle appears to be highly sensitive to muscle contraction even several years after the injury, and in fact it may be more sensitive to mechanical stress than AB muscle. Heightened signaling associated with muscle mechanosensitivity and translation initiation in SCI muscle may be an attempted compensatory response to offset elevated protein degradation in atrophied SCI muscle. Muscle Nerve 50: 599–601, 2014

Neuromuscular Electrical Stimulation–Induced Resistance Training After SCI: A Review of the Dudley Protocol

BACKGROUND Neuromuscular electrical stimulation (NMES), often referred to as functional electrical stimulation (FES), has been used to activate paralyzed skeletal muscle in people with spinal cord injury (SCI). The goal of NMES has been to reverse some of the dramatic losses in skeletal muscle mass, to stimulate functional improvements in people with incomplete paralysis, and to produce some of the health benefits associated with exercise. OBJECTIVE The purpose of this brief review is to describe a quantifiable resistance training form of NMES developed by Gary A. Dudley. METHODS People with motor complete SCI were first tested to confirm that an NMES-induced muscle contraction of the quadriceps muscle could be achieved. The contraction stimulus consisted of biphasic pulses at 35 Hz performed with increasing current up to what was needed to produce full knee extension. Four sets of 10 knee extensions were elicited, if possible. Training occurred biweekly for 3 to 6 months, with ankle weights being increased up to an added weight of 9.1 kg if the 40 repetitions could be performed successfully for 2 sessions. RESULTS Many participants have performed this protocol without adverse events, and all participants showed progression in the number of repetitions and/or the amount of weight lifted. Large increases in muscle mass occur, averaging 30% to 40%. Additional physiological adaptations to stimulated muscle have also been reported. CONCLUSIONS These results demonstrate that the affected skeletal muscle after SCI responds robustly to progressive resistance training many years after injury. Future work with NMES should determine whether gains in lean mass translate to improved health, function, and quality of life.

Heightened TWEAK-NF-κB signaling and inflammation-associated fibrosis in paralyzed muscles of men with chronic spinal cord injury.

Individuals with long-standing spinal cord injury (SCI) often present with extreme muscle atrophy and impaired glucose metabolism at both the skeletal muscle and whole body level. Persistent inflammation and increased levels of proinflammatory cytokines in the skeletal muscle are potential contributors to dysregulation of glucose metabolism and atrophy; however, to date no study has assessed the effects of long-standing SCI on their expression or intracellular signaling in the paralyzed muscle. In the present study, we assessed the expression of genes (TNFαR, TNFα, IL-6R, IL-6, TWEAK, TWEAK R, atrogin-1, and MuRF1) and abundance of intracellular signaling proteins (TWEAK, TWEAK R, NF-κB, and p-p65/p-50/105) that are known to mediate inflammation and atrophy in skeletal muscle. In addition, based on the effects of muscle inflammation on promotion of skeletal muscle fibrosis, we assessed the degree of fibrosis between myofibers and fascicles in both groups. For further insight into the distribution and variability of muscle fiber size, we also analyzed the frequency distribution of SCI fiber size. Resting vastus lateralis (VL) muscle biopsy samples were taken from 11 men with long-standing SCI (≈22 yr) and compared with VL samples from 11 able-bodied men of similar age. Our results demonstrated that chronic SCI muscle has heightened TNFαR and TWEAK R gene expression and NF-κB signaling (higher TWEAK R and phospho-NF-κB p65) and fibrosis, along with substantial myofiber size heterogeneity, compared with able-bodied individuals. Our data suggest that the TWEAK/TWEAK R/NF-κB signaling pathway may be an important mediator of chronic inflammation and fibrotic adaptation in SCI muscle.

Paralytic and non-paralytic muscle adaptations to exercise training vs. high protein diet in individuals with long-standing spinal cord injury

This study compares the effects of an 8-wk isocaloric high-protein (HP) diet versus a combination exercise (Comb-Ex) regimen on paralytic vastus lateralis (VL) and nonparalytic deltoid muscle in individuals with long-standing spinal cord injury (SCI). Fiber-type distribution, cross-sectional area (CSA), levels of translation initiation signaling proteins (Erk-1/2, Akt, p70S6K1, 4EBP1, RPS6, and FAK), and lean thigh mass were analyzed at baseline and after the 8-wk interventions. A total of 11 participants (C5-T12 levels, 21.8 ± 6.3 yr postinjury; 6 Comb-Ex and 5 HP diet) completed the study. Comb-Ex training occurred 3 days/wk and consisted of upper body resistance training (RT) in addition to neuromuscular electrical stimulation (NMES)-induced-RT for paralytic VL muscle. Strength training was combined with high-intensity arm-cranking exercises (1-min intervals at 85-90%, V̇o2peak) for improving cardiovascular endurance. For the HP diet intervention, protein and fat each comprised 30%, and carbohydrate comprised 40% of total energy. Clinical tests and muscle biopsies were performed 24 h before and after the last exercise or diet session. The Comb-Ex intervention increased Type IIa myofiber distribution and CSA in VL muscle and Type I and IIa myofiber CSA in deltoid muscle. In addition, Comb-Ex increased lean thigh mass, V̇o2peak, and upper body strength ( P < 0.05). These results suggest that exercise training is required to promote favorable changes in paralytic and nonparalytic muscles in individuals with long-standing SCI, and adequate dietary protein consumption alone may not be sufficient to ameliorate debilitating effects of paralysis. NEW & NOTEWORTHY This study is the first to directly compare the effects of an isocaloric high-protein diet and combination exercise training on clinical and molecular changes in paralytic and nonparalytic muscles of individuals with long-standing spinal cord injury. Our results demonstrated that muscle growth and fiber-type alterations can best be achieved when the paralyzed muscle is sufficiently loaded via neuromuscular electrical stimulation-induced resistance training.

Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: a pilot, randomized safety and feasibility trial

Study designLongitudinal, randomized study.Objectives(1) Test the safety and feasibility of a ketogenic diet (KD) intervention in the acute stages of spinal cord injury (SCI), (2) assess the effects of a KD on neurological recovery, and (3) identify potential serum biomarkers associated with KD-induced changes in neurological recovery.SettingAcute care and rehabilitation facility.MethodsThe KD is a high-fat, low-carbohydrate diet that includes ≈70–80% total energy as fat. Seven participants with acute complete and incomplete SCI (AIS A–D) were randomly assigned to KD (n = 4) or standard diet (SD, n = 3). Neurological examinations, resting energy expenditure analysis, and collection of blood for evaluation of circulating ketone levels were performed within 72 h of injury and before discharge. Untargeted metabolomics analysis was performed on serum samples to identify potential serum biomarkers that may explain differential responses between groups.ResultsOur pilot findings primarily demonstrated that KD is safe and feasible to be administered in acute SCI. Furthermore, upper extremity motor scores were higher (p < 0.05) in the KD vs. SD group and an anti-inflammatory lysophospholipid, lysoPC 16:0, was present at higher levels, and an inflammatory blood protein, fibrinogen, was present at lower levels in the KD serum samples vs. SD serum samples.ConclusionTaken together, these preliminary results suggest that a KD may have anti-inflammatory effects that may promote neuroprotection, resulting in improved neurological recovery in SCI. Future studies with larger sample size are warranted for demonstrating efficacy of KD for improving neurological recovery.

A high-protein diet or combination exercise training to improve metabolic health in individuals with long-standing spinal cord injury: a pilot randomized study

We compared the effects of an 8‐week iso‐caloric high‐protein (HP) diet versus a combined exercise regimen (Comb‐Ex) in individuals with long‐standing spinal cord injury (SCI). Effects on metabolic profiles, markers of inflammation, and signaling proteins associated with glucose transporter 4 (GLUT‐4) translocation in muscles were evaluated. Eleven participants with SCI completed the study (HP diet: n = 5; Comb‐Ex: n = 6; 46 ± 8 years; C5‐T12 levels; American Spinal Injury Association Impairment Scale A or B). The Comb‐Ex regimen included upper body resistance training (RT) and neuromuscular electrical stimulation‐induced‐RT for paralytic quadriceps muscles, interspersed with high‐intensity (80–90% VO2 peak) arm cranking exercises 3 days/week. The HP diet included ~30% total energy as protein (carbohydrate to protein ratio <1.5, ~30% energy from fat). Oral glucose tolerance tests and muscle biopsies of the vastus lateralis (VL) and deltoid muscles were performed before and after the trial. Fasting plasma glucose levels decreased in the Comb‐Ex (P < 0.05) group compared to the HP‐diet group. A decrease in areas under the curve for insulin and TNF‐α concentrations was observed for all participants regardless of group assignment (time effect, P < 0.05). Although both groups exhibited a quantitative increase in insulin sensitivity as measured by the Matsuda Index, the change was clinically meaningful only in the HP diet group (HP diet: pre, 4.6; post, 11.6 vs. Comb‐Ex: pre, 3.3; post, 4.6). No changes were observed in proteins associated with GLUT‐4 translocation in VL or deltoid muscles. Our results suggest that the HP‐diet and Comb‐Ex regimen may improve insulin sensitivity and decrease TNF‐α concentrations in individuals with SCI.

Differences in glucose metabolism among women with spinal cord injury may not be fully explained by variations in body composition

OBJECTIVE To investigate the differences in glucose metabolism among women with paraplegic, and tetraplegic spinal cord injury (SCI) in comparison to their able-bodied (AB) counterparts after adjusting for differences in body composition. DESIGN Cross-sectional study. After an overnight fast, each participant consumed a 75-g glucose solution for oral glucose tolerance test (OGTT). Blood glucose, insulin, and C-peptide concentrations were analyzed before and 30, 60, 90, and 120 minutes after ingesting glucose solution. Insulin sensitivity index (ISI) was estimated using the Matsuda index. Percentage fat mass (%FM) and total body lean mass (TBLM) were estimated using data from dual-energy x-ray absorptiometry. Visceral fat (VF) was quantified using computed tomography. Outcome measures were compared among groups using analysis of covariance with %FM (or VF) and TBLM as covariates. SETTING Research university. PARTICIPANTS Women (N=42) with SCI (tetraplegia: n=8; paraplegia: n=14) and their race-, body mass index-, and age-matched AB counterparts (n=20). INTERVENTIONS Not applicable. RESULTS At fasting, there was no difference in glucose homeostasis (glucose, insulin, C-peptide concentrations) among 3 groups of women. In contrast, glucose, insulin, and C-peptide concentrations at minute 120 during OGTT were higher in women with tetraplegia versus women with paraplegia and AB women (P<.05, adjusted for TBLM and %FM). In addition, women with tetraplegia had lower ISI (P<.05, adjusted for TBLM and %FM) versus AB women. These differences remained after adjusting for VF and TBLM. CONCLUSION Our study confirms that impaired glucose metabolism among women with tetraplegia may not be fully explained by changes in their body composition. Future studies exploring additional factors involved in glucose metabolism are warranted.

Upper extremity motor training of a subject with initially motor complete chronic high tetraplegia using constraint-induced biofeedback therapy

IntroductionThe purpose of this case study was to determine if a subject with chronic high tetraplegia (C3 AIS A) could learn to use an initially paralyzed upper extremity on the basis of training procedures alone.Case presentationInitially, an AIS examination revealed no purposive movement below the neck other than minimal shoulder movement. Training was carried out weekly over 39 months. Training began based on electromyographic biofeedback; the electrical activity of a muscle (biceps or triceps) was displayed visually on a computer monitor and the subject was encouraged to progressively increase the magnitude of the response in small increments on a trial-by-trial basis (i.e., shaping). When small, overt movements began to appear; these were, in turn, shaped so that their excursion progressively increased. Training then progressed to enable lifting the arm with the aid of the counterweight of a Swedish Help Arm. Mean movement excursions in the best session were: internal rotation 52.5 cm; external rotation 26.9 cm; shoulder extension 22.1 cm; shoulder flexion 15.2 cm; pronation/supination 120°; extension of index finger (D2) 2.5 cm. Movements were initially saltatory, becoming smoother over time. With the Swedish Help Arm, the subject was able to lift her hand an average of 24.3 cm in the best session with 0.7 kg counterweight acting at the wrist (1.9 J of work).DiscussionResults suggest in preliminary fashion the effectiveness of this approach for improving upper extremity function after motor complete high tetraplegia. Thus, future studies are warranted. Possible mechanisms are discussed.