Treadmill Locomotion Research Articles

Grafting of fetal brainstem 5-HT neurons into the sublesional spinal cord of paraplegic rats restores coordinated hindlimb locomotion

In rodent models of spinal cord injury, there is increasing evidence that activation of the locomotor central pattern generator (CPG) below the site of injury with 5-hydroxytryptamine (5-HT) agonists improves locomotor recovery and restores coordination. A promising means of replacing 5-HT control of locomotion is to graft brainstem 5-HT neurons into the spinal cord below the level of the spinal cord injury. However, it is not known whether this approach improves limb coordination because recovery of coordinated stepping has not been documented in detail in previous studies employing this transplantation strategy. Here, adult rats with complete spinal cord transections at the T9/10 level were grafted with E14 fetal neurons from the medulla at the T10/11 vertebra level one month after injury. The B1, B2 and B3 fetal anlagen of brainstem 5-HT neurons, a grouping that included the presumed precursors of recently described 5-HT locomotor command neurons, were used in these grafts. EMG and video recordings of treadmill locomotion evoked by tail stimulation showed full recovery of inter- and intralimb coordination in the grafted rats. We showed, using systemically applied antagonists, that 5-HT2 and 5-HT7 receptors mediate the improved locomotion after grafting, but through actions on different populations of spinal locomotor neurons. Specifically, 5-HT2 receptors control CPG activation as well as motoneuron output, while 5-HT7 receptors contribute primarily to activity of the locomotor CPG. These results are consistent with the roles for these receptors during locomotion in intact rodents and in rodent brainstem–spinal cord in vitro preparations.

Kinematics of treadmill locomotion in mice raised in hypergravity

The study compared the motor performance of adult C57Bl/6J mice previously exposed to a 2G gravity environment during different periods of their development. 12 mice were housed in a large diameter centrifuge from the conception to Postnatal day 10 (P10). Another group of 10 mice was centrifuged form P10 to P30, and a third group of 9 mice was centrifuged from conception to P30. Their gait parameters, and kinematics of joint excursions were compared with 11 control mice, at the age of 2 months using a video-radiographic apparatus connected to a motorized treadmill. The mice that returned to Earth gravity level at the age of P10 showed a motor pattern similar to control mice. At variance the two groups that were centrifuged from P10 to P30 showed a different motor pattern with smaller and faster strides to walk at the same velocity as controls. On the other hand all the centrifuged mice showed significant postural changes, particularly with a more extended ankle joint, but the mice centrifuged during the whole experimental period differed even more. Our results showed that the exposure to hypergravity before P10 sufficed to modify the posture, suggesting that postural control starts before the onset of locomotion, whereas the gravity constraint perceived between P10 and P30 conditioned the tuning of quadruped locomotion with long term consequences. These results support the existence of a critical period in the acquisition of locomotion in mice.

THE EVOLUTION OF LOCOMOTOR RHYTHMICITY IN TETRAPODS

Differences in rhythmicity (relative variance in cycle period) among mammal, fish, and lizard feeding systems have been hypothesized to be associated with differences in their sensorimotor control systems. We tested this hypothesis by examining whether the locomotion of tachymetabolic tetrapods (birds and mammals) is more rhythmic than that of bradymetabolic tetrapods (lizards, alligators, turtles, salamanders). Species averages of intraindividual coefficients of variation in cycle period were compared while controlling for gait and substrate. Variance in locomotor cycle periods is significantly lower in tachymetabolic than in bradymetabolic animals for datasets that include treadmill locomotion, non-treadmill locomotion, or both. When phylogenetic relationships are taken into account the pooled analyses remain significant, whereas the non-treadmill and the treadmill analyses become nonsignificant. The co-occurrence of relatively high rhythmicity in both feeding and locomotor systems of tachymetabolic tetrapods suggests that the anatomical substrate of rhythmicity is in the motor control system, not in the musculoskeletal components.

Characteristics of Gait Ataxia in δ2 Glutamate Receptor Mutant Mice, ho15J

The cerebellum plays a fundamental, but as yet poorly understood, role in the control of locomotion. Recently, mice with gene mutations or knockouts have been used to investigate various aspects of cerebellar function with regard to locomotion. Although many of the mutant mice exhibit severe gait ataxia, kinematic analyses of limb movements have been performed in only a few cases. Here, we investigated locomotion in ho15J mice that have a mutation of the δ2 glutamate receptor. The cerebellum of ho15J mice shows a severe reduction in the number of parallel fiber-Purkinje synapses compared with wild-type mice. Analysis of hindlimb kinematics during treadmill locomotion showed abnormal hindlimb movements characterized by excessive toe elevation during the swing phase, and by severe hyperflexion of the ankles in ho15J mice. The great trochanter heights in ho15J mice were lower than in wild-type mice throughout the step cycle. However, there were no significant differences in various temporal parameters between ho15J and wild-type mice. We suggest that dysfunction of the cerebellar neuronal circuits underlies the observed characteristic kinematic abnormality of hindlimb movements during locomotion of ho15J mice.

Vection in depth during treadmill locomotion

Vection in depth during treadmill locomotion

Effect of Locomotor Training in Completely Spinalized Cats Previously Submitted to a Spinal Hemisection

After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later. Cats were not treadmill trained during the hemispinal period. After spinalization, 5 of 9 cats were not trained and served as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week for 3 weeks. Using detailed kinematic analyses, we showed that, without training, the asymmetrical state of locomotion induced by the hemisection was retained durably after the subsequent spinalization. By contrast, training cats after spinalization induced a reversal of the left/right asymmetries, suggesting that new plastic changes occurred within the spinal cord through locomotor training. Moreover, training was shown to improve the kinematic parameters and the performance of the hindlimb on the previously hemisected side. These results indicate that spinal locomotor circuits, previously modified by past experience such as required for adaptation to the hemisection, can remarkably respond to subsequent locomotor training and improve bilateral locomotor kinematics, clearly showing the benefits of locomotor training in the spinal state.

The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats

Recent studies on the restoration of locomotion after spinal cord injury have employed robotic means of positioning rats above a treadmill such that the animals are held in an upright posture and engage in bipedal locomotor activity. However, the impact of the upright posture alone, which alters hindlimb loading, an important variable in locomotor control, has not been examined. Here we compared the locomotor capabilities of chronic spinal rats when placed in the horizontal and upright postures. Hindlimb locomotor movements induced by exteroceptive stimulation (tail pinching) were monitored with video and EMG recordings. We found that the upright posture alone significantly improved plantar stepping. Locomotor trials using anaesthesia of the paws and air stepping demonstrated that the cutaneous receptors of the paws are responsible for the improved plantar stepping observed when the animals are placed in the upright posture.We also tested the effectiveness of serotonergic drugs that facilitate locomotor activity in spinal rats in both the horizontal and upright postures. Quipazine and (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) improved locomotion in the horizontal posture but in the upright posture either interfered with or had no effect on plantar walking. Combined treatment with quipazine and 8-OH-DPAT at lower doses dramatically improved locomotor activity in both postures and mitigated the need to activate the locomotor CPG with exteroceptive stimulation. Our results suggest that afferent input from the paw facilitates the spinal CPG for locomotion. These potent effects of afferent input from the paw should be taken into account when interpreting the results obtained with rats in an upright posture and when designing interventions for restoration of locomotion after spinal cord injury.

Unmatched perception of speed when running overground and on a treadmill

This study compared the perception of speed between overground and treadmill running. Twenty-one participants ran overground around an athletic track at their preferred speed for 3min, immediately followed by a 3-min treadmill run and a further 3-min overground run. During the treadmill run, participants were blinded to the speed display and were free to adjust the speed until it was perceived similar as their previous self-selected overground speed. A video camera was used to determine the average running speed during each overground run. A one-way ANOVA with repeated measures was used to detect differences among the three speeds: overground speed during session 1 (OG1), perceived overground speed on the treadmill (TM), and overground speed during session 2 (OG2). A significant difference among the three running speeds was found (P=.039). Post hoc analyses showed that the treadmill speed was much slower than both overground speeds but the overground speed did not differ between session 1 and session 2 (OG1: 3.99 (0.78) m/s, TM: 2.73 (0.62) m/s, OG2: 3.80 (0.74) m/s). These findings confirmed that one's perception of speed was influenced by the treadmill on which individuals were unable to match their corresponding self-selected overground running speed. The unmatched perception of speed is likely due to the distortion of normal visual inputs resulting from the discrepancy between observed and expected optic flow. Clinicians, therapists and treadmill users should be aware of the different psychological demands between treadmill and overground locomotion when selecting gait speed.

Variability and Plasticity of Motor Unit Properties in Mammalian Skeletal Muscle

In the majority of mammalian skeletal muscles, contractile properties of motor units are variable and three main types of these units can be distinguished. The present review summarizes: results of studies of motor unit properties in the medial gastrocnemius muscle and their variability in two species, cats and rats, and studies on differences of motor unit properties in two genders. Moreover, plasticity of motor unit properties in rat medial gastrocnemius evoked by two kinds of spinal cord injury, total transection and hemisection, is reviewed, and effects of two types of training, treadmill locomotor and whole-body vibration training, are summarized. Finally, changes in the motor unit properties during the aging process are presented.

Altered patterns of reflex excitability, balance, and locomotion following spinal cord injury and locomotor training.

Spasticity is an important problem that complicates daily living in many individuals with spinal cord injury (SCI). While previous studies in human and animals revealed significant improvements in locomotor ability with treadmill locomotor training, it is not known to what extent locomotor training influences spasticity. In addition, it would be of considerable practical interest to know how the more ergonomically feasible cycle training compares with treadmill training as therapy to manage SCI-induced spasticity and to improve locomotor function. Thus the main objective of our present studies was to evaluate the influence of different types of locomotor training on measures of limb spasticity, gait, and reflex components that contribute to locomotion. For these studies, 30 animals received midthoracic SCI using the standard Multicenter Animal Spinal cord Injury Studies (MASCIS) protocol (10 g 2.5 cm weight drop). They were divided randomly into three equal groups: control (contused untrained), contused treadmill trained, and contused cycle trained. Treadmill and cycle training were started on post-injury day 8. Velocity-dependent ankle torque was tested across a wide range of velocities (612–49°/s) to permit quantitation of tonic (low velocity) and dynamic (high velocity) contributions to lower limb spasticity. By post-injury weeks 4 and 6, the untrained group revealed significant velocity-dependent ankle extensor spasticity, compared to pre-surgical control values. At these post-injury time points, spasticity was not observed in either of the two training groups. Instead, a significantly milder form of velocity-dependent spasticity was detected at postcontusion weeks 8–12 in both treadmill and bicycle training groups at the four fastest ankle rotation velocities (350–612°/s). Locomotor training using treadmill or bicycle also produced significant increase in the rate of recovery of limb placement measures (limb axis, base of support, and open field locomotor ability) and reflex rate-depression, a quantitative assessment of neurophysiological processes that regulate segmental reflex excitability, compared with those of untrained injured controls. Light microscopic qualitative studies of spared tissue revealed better preservation of myelin, axons, and collagen morphology in both locomotor trained animals. Both locomotor trained groups revealed decreased lesion volume (rostro-caudal extension) and more spared tissue at the lesion site. These improvements were accompanied by marked upregulation of BDNF, GABA/GABAb, and monoamines (e.g., norepinephrine and serotonin) which might account for these improved functions. These data are the first to indicate that the therapeutic efficacy of ergonomically practical cycle training is equal to that of the more labor-intensive treadmill training in reducing spasticity and improving locomotion following SCI in an animal model.

Cerebrospinal fluid hypocretin (orexin) levels are elevated by play but are not raised by exercise and its associated heart rate, blood pressure, respiration or body temperature changes.

Hypocretin (Hcrt) has been implicated in the control of motor activity and in respiration and cardiovascular changes. Loss of Hcrt in narcolepsy is linked to sleepiness and to cataplexy, a sudden loss of muscle tone which is triggered by sudden strong emotions. In the current study we have compared the effects of treadmill running, to yard play on cerebrospinal fluid (CSF) Hcrt level in normal dogs. We find that treadmill locomotion, at a wide range of speeds, does not increase Hcrt level beyond baseline, whereas yard play produces a substantial increase in Hcrt, even though both activities produce comparable increases in heart rate, respiration and body temperature. We conclude that motor and cardiovascular changes are not sufficient to elevate CSF levels of Hcrt and we hypothesize that the emotional aspects of yard play account for the observed increase in Hcrt.

Chondroitinase ABC reduces time to muscle reinnervation and improves functional recovery after sciatic nerve transection in rats

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.

A decerebrate adult mouse model for examining the sensorimotor control of locomotion

As wild-type and genetically modified mice are progressively becoming the predominant models for studying locomotor physiology, the technical ability to record sensory and motor components from adult mice, in vivo, are expected to contribute to a better understanding of sensorimotor spinal cord networks. Here, specific technical and surgical details are presented on how to produce an adult decerebrate mouse preparation that can reliably produce sustained bouts of stepping, in vivo, in the absence of anesthetic drugs. Data are presented demonstrating the ability of this preparation to produce stepping during treadmill locomotion, adaptability in its responses to changes in the treadmill speed, and left-right alternation. Furthermore, intracellular recordings from motoneurons and interneurons in the spinal cord are presented from preparations where muscle activity was blocked. Intraaxonal recordings are also presented demonstrating that individual afferents can be recorded using this preparation. These data demonstrate that the adult decerebrate mouse is a tractable preparation for the study of sensorimotor systems.

Functional role of exercise-induced cortical organization of sensorimotor cortex after spinal transection

Spinal cord transection silences neuronal activity in the deafferented cortex to cutaneous stimulation of the body and untreated animals show no improvement in functional outcome (weight-supported stepping) with time after lesion. However, adult rats spinalized since neonates that receive exercise therapy exhibit greater functional recovery and exhibit more cortical reorganization. This suggests that the change in the somatotopic organization of the cortex may be functionally relevant. To address this issue, we chronically implanted arrays of microwire electrodes into the infragranular layers of the hindlimb somatosensory cortex of adult rats neonatally transected at T8/T9 that received exercise training (spinalized rats) and of normal adult rats. Multiple, single neuron activity was recorded during passive sensory stimulation, when the animals were anesthetized, and during active sensorimotor stimulation during treadmill-induced locomotion when the animal was awake and free to move. Our results demonstrate that cortical neurons recorded from the spinalized rats that received exercise 1) had higher spontaneous firing rates, 2) were more likely to respond to both sensory and sensorimotor stimulations of the forelimbs, and also 3) responded with more spikes per stimulus than those recorded from normal rats, suggesting expansion of the forelimb map into the hindlimb map. During treadmill locomotion the activity of neurons recorded from neonatally spinalized rats was greater during weight-supported steps on the treadmill compared with the neuronal activity during nonweight supported steps. We hypothesize that this increased activity is related to the ability of the animal to take weight supported steps and that, therefore, these changes in cortical organization after spinal cord injury are relevant for functional recovery.

Evolution of gait abnormalities in SOD1 G93A transgenic mice

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the loss of upper and lower motoneurons. Clinically, it is manifested by weakness, muscle atrophy and progressive paralysis and ends up with patients' death 2–5 years after diagnosis. Although these symptoms lead in many cases to gait deficits in patients, an exhaustive locomotor profile of animal models mimicking the disease has not been assessed yet. In this work we evaluated the locomotor performance of the SOD1 G93A mouse model of ALS using computerized treadmill gait analysis. SOD1 G93A mice presented early (8 weeks of age) gait abnormalities, evidenced by an increase in the time of the propulsion phase of hindlimb stance. The alterations progressed during the disease until a complete disturbance of normal gait. This finding is meaningful to the field because the identification of a significant difference in a functional endpoint as early as 8 weeks might be a step forward resolving the debate about treatment of mice prior to the symptomatic phase in efficacy studies. These results also point out that digitizing analysis of treadmill locomotion may be useful to evaluate whether new therapeutic approaches are improving functional outcome of the animals.

Kinematic analyses reveal impaired locomotion following injury of the motor cortex in mice

Brain injury in the motor cortex can result in deleterious functional deficits of skilled and fine motor functions. However, in contrast to humans, the destruction of cortex and its descending fibers has been thought not to cause remarkable deficits in simple locomotion in quadropedal animals. In the present study, we aimed to investigate in detail how lesion of the sensorimotor cortex affected locomotion ability in mice using the KinemaTracer system, a novel video-based kinematic analyzer. We found that traumatic injury to the left sensorimotor cortex induced several apparent deficits in the movement of contralesional right limbs during treadmill locomotion. The step length of right limbs decreased, and the speed in the forward direction was abrogated in the swing phase. The coordinates and angle of each joint were also changed after the injury. Some of the abnormal values in these parameters gradually recovered near the control level. The number of cFos-expressing neurons following locomotion significantly decreased in the right side of the spinal cord in injured mice, suggesting a role for cortex and descending fibers in locomotion. In contrast, interlimb coordination did not change remarkably even after the injury, supporting the notion that the basic locomotor pattern was determined by intraspinal neural circuits. These results indicate that the motor cortex and its descending fibers regulate several aspects of fine limb movement during locomotion. Our findings provide practical parameters to assess motor deficits and recovery following cortical injury in mice.

Relationship of High-resolution Triaxial Accelerometry With VO2 In Highly-trained Runners During Treadmill Locomotion

PURPOSE: The use of accelerometers as tools to quantify human movement has become increasingly prevalent in recent years. For estimation of VO2, "Activity Monitors" are typically low resolution, and higher resolution instruments may be of value. The purpose of this study was to determine the test-retest reliability of wireless high frequency, high-resolution accelerometers (HRA), and examine the relationship of HRA signals with VO2 during treadmill locomotion in highly trained runners. METHODS: Procedures were approved by the local HSRC. Seven NCAA D-I distance runners (21.4±1.7yr, 65.5±5.7 kg, 70.1±6.2 ml/kg/min) performed repeated incremental treadmill trials at 1% grade, starting at 2 kph and increasing 2 kph/2 min to volitional exhaustion. This protocol elicited a range of gaits from slow walking to maximal running in these highly trained subjects. Metabolic gasses were collected using an Oxycon Mobile (Viasys, CA). Wireless triaxial HRA (Microstrain, VT) were affixed to subject's lower back and data was streamed at 625 Hz. Raw signal from three axes was integrated to obtain resultant acceleration scalars (RES; Matlab; Mathworks, MA). Root-Mean-Square (RMS), for the last minute of each stage, for Vertical (VT), Medio-Lateral (ML), Fore-Aft (FA) and (RES) were compared to the corresponding minute average of relative VO2 (REL). Pearson's product correlation (r) and coefficient of variation (CV) were determined for VT, LT, FA and RES. Test-retest reliability was examined using Interclass correlations (ICC) and Chronbach's Alpha (SPSS, IL; α = 05). RESULTS: RMS of VT, LT, FA and RES was strongly correlated with REL (r =.87,.88,.95 and.95 respectively; p<.001). CV's were 5.7, 24.4, 24.5 and 5.2% for VT, ML, FA and RES, respectively. Both ICC's and Chronbach's alpha were.98,.97,.97 and.99 for VT, ML, FA and RES. CONCLUSIONS: Test-retest reliability of high frequency HRA displays strong validity and reliability across a wide range of walking/running speeds during treadmill locomotion in highly trained runners. Further, RMS of RES is strongly correlated with VO2, which indicates that RMS of unfiltered HRA is a valid means to determine VO2 during treadmill locomotion. These insights may allow for both clinicians and coaches to effectively monitor subjects for either rehabilitation and/or training purposes.

Differences in Running Mechanics and Economy between Collegiate Runners and Triathletes Identified Using High-Resolution Accelerometers

We have previously reported differences in economy between trained and untrained runners using high-resolution accelerometers (HRA) and indirect calorimetry. In these runners though, differences may have been due to discrepancies in metabolic fitness level. PURPOSE: To determine if HRA could identify differences in economy and mechanics of running between collegiate runners (XC) and triathletes (TRI), of comparable metabolic fitness, during treadmill locomotion. METHODS: Procedures were approved by the Eastern Michigan University CHHS Human Subject Review Committee and subjects gave informed consent. 23 runners, 16 XC (22.1±1.5yr, 66.5±5.7 kg, 71.1±5.2 ml/kg/min) and 8 TRI (25.6±3.8yr, 70.8±3.7 kg, 66.2±4.2 ml/kg/min) performed incremental VO2max trials while wearing HRA (Microstrain, VT; 617 Hz). Aggregate acceleration for vertical (VT), anterior/posterior (AP), medial/lateral (ML), axes were recorded and Euclidian resultants were computed (RES). Trials consisted of 3 min stages starting at 8kph and increasing 2kph until exhaustion. Group comparisons were made from 10-18kph, as all subjects completed these stages. Axial root mean square (RMS), RMS relative to speed (EC), and ratio of RMS/RES (RA) were compared between XC and TRI to identify differences in running mechanics between groups. Expired gases were collected using an Oxycon Mobile (Viasys, CA). VO2 and RER were used to determine O2 cost (O2C) and energy expenditure (EE). MANOVAs were performed using PASW 17.0 (SPSS; IL) α=.05. RESULTS: Total weekly training time (14.8±2.1 hr) was not different between groups but XC ran significantly more than TRI(13.5±1.9 vs. 5.6±1.5 hr). All HRA parameters (RMS, EC, RA) were significantly greater for XC vs. TRI in VT, and lower (p<.05) for XC vs. TRI in ML and AP, except MLRA. Significant speed by group interactions (p<.05) were also present for all HRA parameters except MLEC and MLRA. RER was not different between groups (.91±0)indicating similar fitness for XC and TRI, but VO2 and EE were significantly higher for TRI vs. XC (47.4±.5 vs. 40.8±.3 ml/kg/min and.23±.0 vs.20±.0 kcal/kg/min). CONCLUSION: These data show that XC accelerate more in the VT but less in the AP than TRI. Therefore improved running economy with training may come more from reduced accelerations in AP than VT or ML.

Mild musculoskeletal and locomotor alterations in adult rats with white matter injury following prenatal ischemia

Early brain injury including white matter damage (WMD) appears strongly correlated to perinatal hypoxia-ischemia and adverse neurological outcomes in preterm survivors. Indeed, WMD has been widely associated with subtle to major motor disturbances, sensory, behavioral and cognitive impairments in preterm infants who afterward develop cerebral palsy (CP). Prenatal ischemia (PI) has been shown to reproduce the main features of WMD observed in preterm infants. The present study was aimed at determining in adult rats the impact of PI on brain axons, musculoskeletal histology and locomotor activity. PI was induced by unilateral intrauterine artery ligation at E17 in pregnant rats. We found axonal degeneration and reactive astrogliosis in several white matter regions of adult PI rats. We found mild myopathic and secondary joint changes, including increased variability in myofiber size in several hind limb muscles, decreased myofibers numbers but increased Pax 7 cells and myofiber size in the gastrocnemius, and mild knee and ankle chondromalacia. Although treadmill locomotion appeared normal, several kinematic parameters, such as stride length, amplitude, velocity and leg joint angles were altered in adult PI rats compared to shams. Using intra- and inter-group variability of kinematic parameters, PI seemed to impair the maturation of locomotion on the treadmill. In addition, PI rats exhibited spontaneous hyperactivity in open-field test. Musculoskeletal changes appeared concomitant with mild impairments in gait and posture. Our rodent model of WMD based on PI reproduces the mild motor deficits and musculoskeletal changes observed in many preterm infants with a perinatal history of hypoxia-ischemia, and contributes towards a better understanding of the interplay between brain injury, musculoskeletal histopathology and gait disturbances encountered subsequently.

Effect of slope and sciatic nerve injury on ankle muscle recruitment and hindlimb kinematics during walking in the rat

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.