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The common neurotrophin receptor, p75NTR , has been proposed to be an inhibitor of axon regeneration after peripheral nerve injury, but whether this effect is on the regenerating axons, immune cells migrating into the injury site, or cells in the pathway surrounding the axons is not clear. Cut nerves in mice expressing fluorescent proteins in axons were repaired with grafts from non-fluorescent hosts to study axon elongation when p75NTR was eliminated separately from axons and immune cells in the proximal stump of cut nerves, from cells in the regeneration pathway, or both. Two weeks later, axons from wild type mice regenerating into grafts devoid of p75NTR had elongated more than twice as far as axons in grafts from wild type mice. No enhancement of regeneration of axons in p75NTR knockout mice was observed, whether nerves were repaired with grafts from wild type mice or from p75NTR knockout mice. To evaluate whether inhibition of p75NTR could be used to improve regeneration, nerves in wild type mice repaired without grafts were exposed to a specific inhibitor of the p75NTR receptor, LM11A-31, at the time of nerve repair. This local blockade of p75NTR resulted in successful regeneration of axons of nearly three times as many motoneurons and reinnervation of twice as many muscle fibers by regenerating motor axons as untreated controls. Expression of p75NTR surrounding regenerating axons contributes to poor regeneration during the first 2 weeks after peripheral nerve injury. Inhibition of p75NTR might be a therapeutic target for treatments of peripheral nerve injuries.

BACKGROUND Downslope walking (DSW) is an eccentric-based exercise intervention that promotes neuroplasticity of spinal reflex circuitry by inducing depression of Soleus Hoffman (H)-reflexes in young, neurologically unimpaired adults. OBJECTIVE The objective of the study was to evaluate the effects of DSW on spinal excitability (SE) and walking function (WF) in people with multiple sclerosis (PwMS). METHODS Our study comprised two experiments on 12 PwMS (11 women; 45.3±11.8 years). Experiment 1 evaluated acute effects of a single 20-minute session of treadmill walking at three different walking grades on SE, 0% or level walking (LW), - 7.5% DSW, and - 15% DSW. Experiment 2 evaluated the effects of 6 sessions of DSW, at - 7.5% DSW (with second session being - 15% DSW) on SE and WF. RESULTS Experiment 1 showed significantly greater acute % H-reflex depression following - 15% DSW compared to LW (p = 0.02) and - 7.5% DSW (p = 0.05). Experiment 2 demonstrated significant improvements in WF. PwMS who showed greater acute H-reflex depression during the - 15% DSW session also demonstrated greater physical activity, long-distance WF, and the ability to have greater H-reflex depression after DSW training. Significant changes were not observed in regards to SE. CONCLUSIONS Though significant changes were not observed in SE after DSW training, we observed an improvement in WF which merits further investigation of DSW in PwMS.

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can be used to evaluate descending corticomotor influences on spinal reflex excitability through modulation of the Hoffman reflex (H-reflex). The purpose of this study was to characterize between-session reliability of cortical, spinal, and cortical-conditioned spinal excitability measures collected from the soleus muscle. Thirteen able-bodied young adult participants were tested over four sessions. Intraclass correlation coefficients were calculated to quantify between-session reliability of active motor threshold (AMT), unconditioned H-reflexes (expressed as a percentage of Mmax), and conditioned H-reflexes using short-latency facilitation (SLF) and long-latency facilitation (LLF). Pearson correlation coefficients were calculated to assess associations between H-reflex facilitation and unconditioned H-reflex amplitude. Between-session reliability for SLF (ICC = 0.71) was higher than for LLF (ICC = 0.45), was excellent for AMT (ICC = 0.95), and was moderate for unconditioned H-reflexes (ICC = 0.63). Our results suggest moderate-to-good reliability of SLF and LLF to evaluate cortical influences on spinal reflex excitability across multiple testing sessions in able-bodied individuals.

This article outlines the novel hypothesis that exercise promotes axon regeneration after peripheral nerve injury through neuronal brain-derived neurotrophic factor (BDNF), and there are three required means of promoting BDNF expression: 1) increased signaling through androgen receptors, 2) increased cAMP-responsive element-binding protein expression, and 3) increased expression of the transcription factor SRY-box containing gene 11.

Downslope walking (DSW) causes H-reflex depression in healthy adults, and thus may hold promise for inducing spinal reflex plasticity in people with Multiple Sclerosis (PwMS). The study purpose was to test the hypothesis that DSW will cause acute depression of spinal excitability in PwMS. Soleus H-reflexes were measured in PwMS (n = 18) before and after 20 min of treadmill walking during three visits. Participants walked on a different slope each visit [level: 0% level walking (LW), upslope: +7.5% treadmill walking with an upslope (USW) or downslope: −7.5% (DSW)]. The soleus Hmax/Mmax ratio was used to measure spinal excitability. Heart rate and ratings of perceived exertion (RPE) were measured during walking. DSW induced the largest change in spinal excitability (a 26.7% reduction in soleus Hmax/Mmax (p = 0.001)), although LW also reduced Hmax/Mmax (-5.3%, p = 0.05). Heart rate (p

The pathological complications of atherosclerosis, namely heart attacks and strokes, remain the leading cause of mortality in the Western world. Preceding atherosclerosis is endothelial dysfunction. There is therefore interest in the application of non-invasive clinical tools to assess endothelial function. The flow-mediated dilation (FMD) test is the standard tool used to assess endothelial function. Reduced FMD is an early marker of atherosclerosis and has been noted for its capacity to predict future cardiovascular disease events. This review discusses the measurement of endothelial function using ultrasound, with a focus on the FMD technique.

Full functional recovery after traumatic peripheral nerve injury is rare. We postulate three reasons for the poor functional outcome measures observed. Axon regeneration is slow and not all axons participate. Significant misdirection of regenerating axons to reinnervate inappropriate targets occurs. Seemingly permanent changes in neural circuitry in the central nervous system are found to accompany axotomy of peripheral axons. Exercise in the form of modest daily treadmill training impacts all three of these areas. Compared to untrained controls, regenerating axons elongate considerably farther in treadmill trained animals and do so via an autocrine/paracrine neurotrophin signaling pathway. This enhancement of axon regeneration takes place without an increase in the amount of misdirection of regenerating axons found without training. The enhancement also occurs in a sex-dependent manner. Slow continuous training is effective only in males, while more intense interval training is effective only in females. In treadmill trained, but not untrained mice the extent of coverage of axotomized motoneurons is maintained, thus preserving important elements of the spinal circuitry.

The validity of the flow-mediated dilation (FMD) test has been doubted due to the lack of normalization to the primary stimulus, shear stress. Shear stress can be calculated using a simplified mathematical model based on Poiseuille’s law. Poiseuille’s law assumes that the blood velocity profile is parabolic. The presence of turbulence will violate this assumption. The Reynolds number (RE) is used to define critical values for the transition from laminar to turbulent flow. Between RE values of 2000 and 4000, flow enters a transitional phase where turbulence is possible. Purpose: To determine whether brachial artery blood flow becomes turbulent during reactive hyperemia following forearm ischemia. Methods: Eleven healthy male subjects (25 ± 5 years) were tested. Brachial artery diameters and blood velocities were measured continuously following 2, 4, 6 and 10 minutes ischemia. The peak post-ischemic RE (REpeak) and RE integrated over 40 seconds (RE40) post-ischemia were calculated. Results: There was a significant change in REpeak (F4,7 = 98.573, p = ≤ 0.001) and RE40) (F4,7) = 50.613, p = ≤ 0.001) in response to ischemia. Within-subjects contrasts revealed a significant increase in REpeak and RE40 for each duration of ischemia versus baseline (p = ≤ 0.001). Following 4 minutes of ischemia there was approximately 12 seconds of potentially turbulent flow. Conclusion: Blood flow transitions between laminar and turbulent flow during ischemia-induced reactive hyperemia. This may limit the efficacy of estimating shear stress when using the standard FMD test protocol.

We investigated the extent of misdirection of regenerating axons when that regeneration was enhanced using treadmill training. Retrograde fluorescent tracers were applied to the cut proximal stumps of the tibial and common fibular nerves two or four weeks after transection and surgical repair of the mouse sciatic nerve. The spatial locations of retrogradely labeled motoneurons were studied in untreated control mice and in mice receiving two weeks of treadmill training, either according to a continuous protocol (10 m/min, one hour/day, five day/week) or an interval protocol (20 m/min for two minutes, followed by a five minute rest, repeated 4 times, five days/week). More retrogradely labeled motoneurons were found in both treadmill trained groups. The magnitude of this increase was as great as or greater than that found after using other enhancement strategies. In both treadmill trained groups, the proportions of motoneurons labeled from tracer applied to the common fibular nerve that were found in spinal cord locations reserved for tibial motoneurons in intact mice was no greater than in untreated control mice and significantly less than found after electrical stimulation or chondroitinase treatment. Treadmill training in the first two weeks following peripheral nerve injury produces a marked enhancement of motor axon regeneration without increasing the propensity of those axons to choose pathways leading to functionally inappropriate targets.

Animal studies have identified monocyte chemoattractive protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) as critical mediators of arterial diameter enlargement in response to chronic increases in blood flow (arteriogenesis). Furthermore, cellular studies have shown that the shear stresses resulting from increased blood flow stimulate synthesis of MCP-1, which in turn stimulates synthesis of VEGF. The purpose of this study was to determine if these mechanisms are evident in healthy women. Resting femoral artery diameter and blood flow, lean leg mass, MCP-1 and VEGF concentrations, and aerobic capacity were measured in 34 healthy women along with plasma concentrations of lipids associated with cardiovascular disease risk. Femoral artery diameter was independently related to metabolically active (lean) leg mass (b=0.41, P=0.008) and aerobic capacity (b=0.45, P=0.004). Plasma MCP-1 correlated negatively with the ratio of femoral artery diameter to lean leg mass (b=-0.42, P=0.009) and positively with serum triglycerides (b=0.46, P=0.005). Plasma VEGF exhibited similar correlations and strongly correlated with MCP-1 (R=0.92, P

Physical activity after spinal cord injury promotes improvements in motor function, but its effects following peripheral nerve injury are less clear. Although axons in peripheral nerves are known to regenerate better than those in the CNS, methods of accelerating regeneration are needed due to the slow overall rate of growth. Therefore we studied the effect of two weeks of treadmill locomotion on the growth of regenerating axons in peripheral nerves following injury. The common fibular nerves of thy-1-YFP-H mice, in which a subset of axons in peripheral nerves express yellow fluorescent protein (YFP), were cut and repaired with allografts from non-fluorescent littermates, and then harvested two weeks later. Mice were divided into groups of low-intensity continuous training (CT, 60 minutes), low-intensity interval training (IT; one group, 10 reps, 20 minutes total), and high-intensity IT (three groups, 2, 4, and 10 reps). One repetition consisted of two minutes of running and five minutes of rest. Sixty minutes of CT resulted in the highest exercise volume, whereas two reps of IT resulted in the lowest volume of exercise. The lengths of regenerating YFP+ axons were measured in images of longitudinal optical sections of nerves. Axon profiles were significantly longer than control in all exercise groups except the low-intensity IT group. In the CT group and the high-intensity IT groups that trained with four or 10 repetitions axons were more than twice as long as unexercised controls. The number of intervals did not impact axon elongation. Axon sprouting was enhanced in IT groups but not the CT group. Thus exercise, even in very small quantities, increases axon elongation in injured peripheral nerves whereas continuous exercise resulting in higher volume (total steps) may have no net impact on axon sprouting.

Electrical stimulation of cut peripheral nerves at the time of their surgical repair results in an enhancement of axon regeneration. Regeneration of axons through nerve allografts was used to evaluate whether this effect is due to an augmentation of cell autonomous neurotrophin signaling in the axons or signaling from neurotrophins produced in the surrounding environment. In the thy-1-YFP-H mouse, a single one hour application of electrical stimulation at the time of surgical repair of the cut common fibular nerve results in a significant increase in the proportion of YFP+ dorsal root ganglion neurons that were also immunoreactive for BDNF or trkB as well as an increase in the length of regenerating axons through allografts from wild type litter mates, both one and two weeks later. Axon growth through allografts from neurotrophin-4/5 knockout mice or grafts made acellular by repeated cycles of freezing and thawing is normally very poor, but electrical stimulation results in a growth of axons through these grafts which is similar to that observed through grafts from wild type mice after electrical stimulation. When cut nerves in NT-4/5 knockout mice were electrically stimulated, no enhancement of axon regeneration was found. Electrical stimulation thus produces a potent enhancement of the regeneration of axons in cut peripheral nerves which is independent of neurotrophin production by cells in their surrounding environment but is dependent on stimulation of trkB and its ligands in the regenerating axons themselves.

The purpose of this study was to test the hypothesis that downslope treadmill walking decreases spinal excitability. Soleus H-reflexes were measured in sixteen adults on 3 days. Measurements were taken before and twice after 20 min of treadmill walking at 2.5 mph (starting at 10 and 45 min post). Participants walked on a different slope each day [level (Lv), upslope (Us) or downslope (Ds)]. The tibial nerve was electrically stimulated with a range of intensities to construct the M-response and H-reflex curves. Maximum evoked responses (Hmax and Mmax) and slopes of the ascending limbs (Hslp and Mslp) of the curves were evaluated. Rate-dependent depression (RDD) was measured as the % depression of the H-reflex when measured at a rate of 1.0 Hz versus 0.1 Hz. Heart rate (HR), blood pressure (BP), and ratings of perceived exertion (RPE) were measured during walking. Ds and Lv walking reduced the Hmax/Mmax ratio (P = 0.001 & P = 0.02), although the reduction was larger for Ds walking (29.3 ± 6.2% vs. 6.8 ± 5.2%, P = 0.02). The reduction associated with Ds walking was correlated with physical activity level as measured via questionnaire (r = −0.52, P = 0.04). Us walking caused an increase in the Hslp/Mslp ratio (P = 0.03) and a decrease in RDD (P = 0.04). These changes recovered by 45 min. Exercise HR and BP were highest during Us walking. RPE was greater during Ds and Us walking compared to Lv walking, but did not exceed “Fairly light” for Ds walking. In conclusion, in healthy adults treadmill walking has a short-term effect on soleus H-reflex excitability that is determined by the slope of the treadmill surface.

The purpose of the study was to determine whether arterial diameter, flow-mediated dilatation (FMD), and arterial range are affected by spinal cord injury (SCI). We assessed arm (radial) and leg (posterior-tibial) arteries that are comparable in size and function to determine whether (a) arterial function is reduced in individuals with SCI vs nondisabled subjects and (b) decrements to SCI arterial function are greater in the legs vs arms.Eighteen men with chronic (9.8 +/- 6.3 years) SCI (T2 to T11; American Spinal Injury Association A) and 13 nondisabled subjects matched for age (33.1 +/- 4.8 vs 29.8 +/- 8.2 years old, respectively), height, and weight (BMI = 25.3 +/- 5.8 vs 26.6 +/- 5.5 kg/m2, respectively).Radial and posterior tibial artery B-mode ultrasound images were continuously captured to measure resting diameter, occluded diameter, and postischemic diameters. Hierarchical linear modeling accounted for the nested experimental design.Individuals with SCI have lower systemic (arm + leg) FMD than nondisabled subjects (9.3% vs 12.3%, respectively; P= 0.035), primarily because of reduced leg FMD (11.5 +/- 3.1% vs 7.0 +/- 2.8% for SCI arms vs legs, respectively; P = 0.010). Persons with SCI also had lower arterial range than nondisabled subjects (0.79 vs 1.00 mm, respectively; P = 0.043), primarily because of the legs (0.81 +/- 0.09 vs 0.56 +/- 0.11 mm for SCI arms vs legs, respectively; P = 0.030).Leg arterial function seems to deteriorate at greater rates compared to the arms for individuals with SCI. Interventions to improve cardiovascular health should include measurements taken in the legs.

Longitudinal. The purpose of this study was to evaluate the effect of lower extremity resistance training on quadriceps fatigability, femoral artery diameter, and femoral artery blood flow. Academic Institution. Five male chronic spinal cord injury (SCI) individuals (American Spinal Injury Association (ASIA): A complete; C5–T10; 36±5 years old) completed 18 weeks of home-based neuromuscular electrical stimulation (NMES) resistance training. Subjects trained the quadriceps muscle group twice a week with four sets of 10 dynamic knee extensions against resistance while in a seated position. All measurements were made before training and after 8, 12, and 18 weeks of training. Ultrasound was used to measure femoral artery diameter and blood flow. Blood flow was measured before and after 5 and 10 min of distal cuff occlusion, and during a 4-min isometric electrical stimulation fatigue protocol. Training resulted in significant increases in weight lifted and muscle mass, as well as a 60% reduction in muscle fatigue (P=0.001). However, femoral arterial diameter did not increase. The range was 0.44±0.03 to 0.46±0.05 cm over the four time points (P=0.70). Resting, reactive hyperemic, and exercise blood flow did not appear to change with training. NMES resistance training improved muscle size and fatigue despite an absence of response in the supplying vasculature. These results suggest that the decreases in arterial caliber and blood flow seen with SCI are not tightly linked to muscle mass and fatigue resistance. In addition, muscle fatigue in SCI patients can be improved without increases in arterial diameter or blood flow capacity. Grants HL65179, HD39676, and HD39676S2.

The pathological complications of atherosclerosis, namely heart attacks and strokes, remain the leading cause of mortality in the Western world (Lloyd-Jones & Adams et al. 2010). Preceding atherosclerosis is endothelial dysfunction (Ross 1993; Cohn 1999; Quyyumi 2003). The endothelium comprises a continuous monolayer of cells which separate the vascular wall from the circulation (Lerman & Zeiher 2005). Disruption of this essential monolayer is thought to occur early in the pathogenesis of cardiovascular disease (CVD). There is, therefore, interest in the application of non-invasive clinical tools to assess the function and health of this essential monolayer.

Flow-mediated dilation (FMD) is the standard tool used to assess endothelial function. The premise behind the standard FMD test is that it serves as an endothelial-dependant nitric oxide bioassay; however, the endothelium may release additional dilatory molecules which contribute to FMD, most notably prostacyclin and endothelial-derived hyperpolarizing factor. The relative importance of these molecules to the dilatory response may vary substantially among individuals, particularly in response to a number of diseased states. This review discusses how each of these molecules may contribute to vasodilation, and considers the circumstances in which they may vary.

The validity of the flow-mediated dilation test has been questioned due to the lack of normalization to the primary stimulus, shear stress. Shear stress can be calculated using Poiseuille's law. However, little attention has been given to the most appropriate blood velocity parameter(s) for calculating shear stress. The pulsatile nature of blood flow exposes the endothelial cells to two distinct shear stimuli during the cardiac cycle: a large rate of change in shear at the onset of flow (velocity acceleration), followed by a steady component. The parameter typically entered into the Poiseuille's law equation to determine shear stress is time-averaged blood velocity, with no regard for flow pulsatility. This paper will discuss (1) the limitations of using Posieuille's law to estimate shear stress and (2) the importance of the velocity profile—with emphasis on velocity acceleration—to endothelial function and vascular tone.

Application of chondroitinase ABC (ChABC) to injured peripheral nerves improves axon regeneration, but it is not known whether functional recovery is also improved. Recordings of EMG activity [soleus (Sol) M response and H reflexes] evoked by nerve stimulation and of Sol and tibialis anterior (TA) EMG activity and hindlimb and foot kinematics during slope walking were made to determine whether ChABC treatment of the sciatic nerve at the time of transection improves functional recovery. Recovery of evoked EMG responses began as multiple small responses with a wide range of latencies that eventually coalesced into one or two more distinctive and consistent responses (the putative M response and the putative H reflex) in both groups. Both the initial evoked responses and the time course of their maturation returned sooner in the ChABC group than in the untreated (UT) group. The reinnervated Sol and TA were coactivated during treadmill locomotion during downslope, level, and upslope walking throughout the study period in both UT and ChABC-treated rats. By 10 wk after nerve transection and repair, locomotor activity in Sol, but not TA, had returned to its pretransection pattern. There was an increased reliance on central control of Sol activation across slopes for both groups as interpreted from elevated prestance Sol EMG activity that was no longer modulated with slope. Limb length and orientation during locomotion were similar to those observed prior to nerve injury during upslope walking only in the ChABC-treated rats. Thus treatment of cut nerves with ChABC leads to improvements in functional recovery.

Exercise in the form of daily treadmill training results in significant enhancement of axon regeneration following peripheral nerve injury. Because androgens are also linked to enhanced axon regeneration, we wanted to investigate whether sex differences in the effect of treadmill training might exist. The common fibular nerves of thy-1-YFP-H mice were cut and repaired with a graft of the same nerve from a strain-matched wild type donor mouse. Animals were treated with one of two daily treadmill training paradigms: slow continuous walking for one hour or four higher intensity intervals of two minutes duration separated by five minute rest periods. Training was begun on the third day following nerve injury and continued five days per week for two weeks. Effects on regeneration were evaluated by measuring regenerating axon profile lengths in optical sections through the repair sites and grafts at the end of the training period. No sex differences were found in untrained control mice. Continuous training resulted in significant enhancement of axon regeneration only in males. No effect was found in females or in castrated males. Interval training was effective in enhancing axon regeneration only in females and not in intact males or castrated males. Untrained females treated with the aromatase inhibitor, anastrozole, had significant enhancement of axon regeneration without increasing serum testosterone levels. Two different mechanisms exist to promote axon regeneration in a sex-dependent manner. In males treadmill training utilizes testicular androgens. In females a different cellular mechanism for the effect of treadmill training must exist.

The role of neurotrophin-4/5 in the enhancement of axon regeneration in peripheral nerves produced by treadmill training was studied in mice. Common fibular nerves of animals of the H strain of thy-1-YFP mice, in which a subset of axons in peripheral nerves is marked by the presence of yellow fluorescent protein, were cut and surgically repaired using nerve grafts from non-fluorescent mice. Lengths of profiles of fluorescent regenerating axons were measured using optical sections made through whole mounts of harvested nerves. Measurements from mice that had undergone one hour of daily treadmill training at modest speed (10 m/min) were compared to those of untrained (control) mice. Modest treadmill training resulted in fluorescent axon profiles that were nearly twice as long as controls at one, two and four week survival times. Similar enhanced regeneration was found when cut nerves of wild type mice were repaired with grafts from neurotrophin-4/5 knockout mice or grafts made acellular by repeated freezing/thawing. No enhancement was produced by treadmill training in neurotrophin-4/5 knockout mice, irrespective of the nature of the graft used to repair the cut nerve. Much as had been observed previously for the effects of brief electrical stimulation, the effects of treadmill training on axon regeneration in cut peripheral nerves are independent of changes produced in the distal segment of the cut nerve and depend on the promotion of axon regeneration by changes in NT-4/5 expression by cells in the proximal nerve segment.

In this study, patterns of activity in the soleus (Sol) and tibialis anterior (TA) muscles and hindlimb kinematics were evaluated during slope walking in rats after transection and surgical repair either of the entire sciatic nerve (Sci group) or of its two branches separately, the tibial and common fibular nerves (T/CF group). With the latter method, axons from the tibial and common fibular nerves could not reinnervate targets of the other nerve branch after injury, reducing the opportunity for misdirection. Activity in the TA shifted from the swing phase in intact rats to nearly the entire step cycle in both injured groups. Since these changes occur without misdirection of regenerating axons, they are interpreted as centrally generated. Sol activity was changed from reciprocal to that of TA in intact rats to coactivate with TA, but only in the Sci group rats. In the T/CF group rats, Sol activity was not altered from that observed in intact rats. Despite effects of injury that limited foot movements, hindlimb kinematics were conserved during downslope walking in both injury groups and during level walking in the T/CF group. During level walking in the Sci group and during upslope walking in both groups of injured rats, the ability to compensate for the effects of the nerve injury was less effective and resulted in longer limb lengths held at more acute angles throughout the step cycle. Changes in limb movements occur irrespective of axon misdirection and reflect compensatory changes in the outputs of the neural circuits that drive locomotion.

Slope-related differences in hindlimb movements and activation of the soleus and tibialis anterior muscles were studied during treadmill locomotion in intact rats and in rats 4 and 10 weeks following transection and surgical repair of the sciatic nerve. In intact rats, the tibialis anterior and soleus muscles were activated reciprocally at all slopes, and the overall intensity of activity in tibialis anterior and the mid-step activity in soleus increased with increasing slope. Based on the results of principal components analysis, the pattern of activation of soleus, but not of tibialis anterior, changed significantly with slope. Slope-related differences in hindlimb kinematics were found in intact rats, and these correlated well with the demands of walking up or down slopes. Following recovery from sciatic nerve injury, the soleus and tibialis anterior were co-activated throughout much of the step cycle and there was no difference in intensity or pattern of activation with slope for either muscle. Unlike intact rats, these animals walked with their feet flat on the treadmill belt through most of the stance phase. Even so, during downslope walking limb length and limb orientation throughout the step cycle were not significantly changed from values found in intact rats. This conservation of hindlimb kinematics was not observed during level or upslope walking. These findings are interpreted as evidence that the recovering animals adopt a novel locomotor strategy that involves stiffening of the ankle joint by antagonist co-activation and compensation at more proximal joints. Their movements are most suitable to the requirements of downslope walking but the recovering rats lack the ability to adapt to the demands of level or upslope walking.

Poor functional recovery found after peripheral nerve injury has been attributed to the misdirection of regenerating axons to reinnervate functionally inappropriate muscles. We applied brief electrical stimulation (ES) to the common fibular (CF) but not the tibial (Tib) nerve just prior to transection and repair of the entire rat sciatic nerve, to attempt to influence the misdirection of its regenerating axons. The specificity with which regenerating axons reinnervated appropriate targets was evaluated physiologically using compound muscle action potentials (M responses) evoked from stimulation of the two nerve branches above the injury site. Functional recovery was assayed using the timing of electromyography (EMG) activity recorded from the tibialis anterior (TA) and soleus (Sol) muscles during treadmill locomotion and kinematic analysis of hindlimb locomotor movements. Selective ES of the CF nerve resulted in restored M-responses at earlier times than in unstimulated controls in both TA and Sol muscles. Stimulated CF axons reinnervated inappropriate targets to a greater extent than unstimulated Tib axons. During locomotion, functional antagonist muscles, TA and Sol, were coactivated both in stimulated rats and in unstimulated but injured rats. Hindlimb kinematics in stimulated rats were comparable to untreated rats, but significantly different from intact controls. Selective ES promotes enhanced axon regeneration but does so with decreased fidelity of muscle reinnervation. Functional recovery is neither improved nor degraded, suggesting that compensatory changes in the outputs of the spinal circuits driving locomotion may occur irrespective of the extent of misdirection of regenerating axons in the periphery.

Cigarette smoking is associated with impaired arterial function as measured by reduced vasodilation in response to reactive hyperemia. However, previous studies did not account for potential differences in shear stimuli. The purpose of this study was to use young, occasional smokers to ethically evaluate the effects of acute and chronic smoking on shear rate-diameter dose-response slopes. Young (20 to 26-y-old) nonsmokers (n = 9) and occasional (1 pack/week) smokers were tested (n = 9). Smokers were tested after abstaining for 2 or more d and then immediately after smoking two cigarettes. Shear rate was manipulated using five upstream ischemic durations (0.5, 1, 2, 5 and 10 min). Radial artery blood velocities and diameters were assessed using Doppler ultrasound. Hierarchical linear modeling (HLM) was used to estimate change in diameter using repeated measures of shear rate nested within each subject. The shear rate-diameter slope was reduced by 35.9% in occasional smokers compared with nonsmoking controls (beta = 2.78(10-4) versus 1.78(10-4), p = 0.004). Acute smoking further attenuated the shear rate-diameter slope (i.e., arterial function) by 23.8% (beta = 1.79(10-4) versus 1.36(10-4), p = 0.037). These results suggest that repeated bouts of occasional cigarette smoking can chronically attenuate arterial function in otherwise healthy, young persons.

Repeated measures training intervention.To evaluate the effects of neuromuscular electrical stimulation (NMES)-induced resistance exercise therapy on lower extremity arterial health in individuals with chronic, complete spinal cord injury (SCI). We define "arterial health" using three surrogate markers: (a) resting diameter, (b) flow-mediated dilation (FMD), and (c) arterial range.Department of Kinesiology, University of Georgia, USA.We assessed five 36+/-5-year-old male individuals with chronic, complete SCI before, during, and after 18 weeks of training. The quadriceps femoris muscle group of both legs were trained twice a week with 4 x 10 repetitions of unilateral, dynamic knee extensions. The health of the posterior tibial artery was assessed using a B-mode ultrasound unit equipped with a high-resolution video capture device. Proximal occlusion was used to evoke ischemia for 5 min and then for 10 min. FMD was calculated using the peak diameter change (above rest) following 5 min occlusion. Arterial range was calculated using minimum (during occlusion) and maximum diameters (post 10 min occlusion). Hierarchical linear modeling accounted for the nested (repeated measures) experimental design.FMD improved from 0.08+/-0.11 mm (2.7%) to 0.18+/-0.15 mm (6.6%) (P=0.004), and arterial range improved from 0.36+/-0.28 to 0.94+/-0.40 mm (P=0.001), after 18 weeks of training. Resting diameter did not significantly change.Home-based, self-administered NMES resistance exercise therapy consisting of 80 contractions/week improved FMD and arterial range. This provides evidence that resistance exercise therapy can improve arterial health after SCI, which may reduce the risk of future cardiovascular disease.

Manning J. Sabatier, PhD, Lee Stoner, MA, Matt Reifenberger, MA,* Kevin McCully, PhDDepartment of Exercise Science, University of Georgia, Athens, GA 30602Received 23 May 2005; accepted 3 November 2005ABSTRACT: Purpose. The difference between struc-tural remodeling and changes in tone of peripheralarteries in the lower extremities has not been eval-uated. The purpose of this study was to (1) evaluatethe day-to-day reproducibility and interobserver reli-ability (IOR) of posterior tibial artery (PTA) diametermeasurements and (2) evaluate the effect of postureon PTA diameter at rest (Drest), during 10 minutes ofproximal cuff occlusion (Dmin), and after the releaseof cuff occlusion (Dmax), as well as range (Dmax Dmin) and constriction [(Dmax Drest)/(Dmax Dmin) 100] in vivo.Methods. We used B-mode sonography to imagethe PTA during each condition.Results. Day-to-day reliability was good for Drest(intraclass correlation coefficient [ICC] 0.95; mean dif-ference 4.2%), Dmin (ICC 0.93; mean difference 5.4%),and Dmax (ICC 0.99; mean difference 2.2%). The coef-ficient of repeatability for IOR was 70.5 mm, with amean interobserver error of 4.7 mm. The seated posi-tion decreased Drest (2.6 6 0.2 to 2.4 6 0.3 mm; p ¼0.002), increased Dmin (2.1 6 0.2 to 2.4 6 0.2 mm; p ¼0.001), and decreased Dmax (3.1 6 0.4 to 2.8 6 0.3mm; p < 0.001) compared with the supine position.The seated position also decreased arterial range(Dmax Dmin) from 0.9 6 0.2 to 0.5 6 0.1 mm (p ¼0.003) and increased basal arterial constriction from57 6 19% to 105 6 27% (p ¼ 0.007).Conclusions. The system employed for measuringPTA diameter yields unbiased and consistent esti-mates. Furthermore, lower extremity arterial con-striction and range change with posture in a mannerconsistent with known changes in autonomic act-ivity.

Transient changes in arterial diameter in response to transient ischemia-induced changes in arterial blood velocity have been used as an index of vascular health. The purpose of this study was to determine the relationship between blood velocity and diameter in the brachial artery by different methods of increasing blood velocity. Acute cigarette smoking was used with otherwise healthy young occasional smokers to determine the influence of endothelial-nitric oxide pathways on the arterial diameter-blood velocity relationship. Nine nonsmokers and 12 occasional smokers (2 = 0.89). The mean slope of the velocity-diameter relationship was not different between nonsmokers and occasional smokers who abstained from smoking at least 2 days. Acute smoking did not alter the slope of the velocity-diameter relationship although the mean intercept was decreased as a result of consistent vasoconstriction (7–10%). The mechanisms by which smoking impairs vascular health are largely unknown. These findings differ from previous smoking studies that used chronic and/or heavier smokers. The velocity-diameter relationship appears independent of the method for increasing velocity. Acute smoking in occasional smokers results in vasoconstriction without altering vascular responsiveness. The velocity-diameter relationship may be a useful measure of the progression of vascular disease.

WOOD, R. H., R. REYES, M. A. WELSCH, J. FAVALORO-SABATIER, M. SABATIER, C. M. LEE, L. G. JOHNSON, and P. F. HOOPER. Concurrent cardiovascular and resistance training in healthy older adults. Med. Sci. Sports Exerc., Vol. 33, No. 10, 2001, pp. 1751–1758. Purpose: The recommendations for exercise training and physical activity for older adults include cardiovascular and resistance training components (CVT and RT, respectively). The purpose of the present investigation was to compare the fitness benefits of concurrent CVT and RT with those attained through an equivalent duration of CVT or RT alone. Methods: Thirty-six participants (ages 60–84) were assigned to a control group or to one of three exercise treatment groups. The treatment groups exercised three times per week for 12 wk using RT (N = 11), CVT (N = 10), or CVT and RT (BOTH, N = 9). Pre- and post-training, participants performed a submaximal exercise test (GXT), five repetition-maximum strength tests (5RM), and the AAHPERD functional fitness test for older adults. Results: All exercise treatment groups revealed lower resting heart rate and rate-pressure product; lower exercise diastolic blood pressure and rating of perceived exertion; increased GXT duration; increased leg, back, and shoulder 5RM scores; and improved AAHPERD flexibility, coordination, and cardiovascular endurance scores. The exercise treatment groups responded differently on the following: RT and BOTH enhanced arm and chest strength more than CVT; and BOTH enhanced AAHPERD strength and agility scores more than CVT or RT. Conclusions: Concurrent CVT and RT is as effective in eliciting improvements in cardiovascular fitness and 5RM performance as CVT or RT, respectively. Moreover, incorporating both CVT and RT in exercise programs for older adults may be more effective in optimizing aspects of functional fitness than programs that involve only one component.