Kenneth A. Clarke

Gait Analysis in the Mouse

The gait of the adult Swiss (Mike Flack--MF1 subtype) mouse during spontaneous walk/trot locomotion at velocities ranging from 14-43 cm s(-1) has been analysed using simultaneous video and reaction force analysis. No differences were observed between males and females. Velocity adjustments within this range are accounted for to a greater extent (>70%) by stride time decreases and to a lesser degree (<30%) by stride length increases. Equivalent stride times for fore and hindlimbs were, in the former, composed of a shorter stance and a longer swing time. Peak vertical reaction force increases with decreasing stance time, with that for the forelimb being about 5% greater than that for the hindlimb across the whole stance time range studied. The areas under the vertical reaction force curves for fore and hindlimbs are, however, not significantly different. The results are discussed in the light of in vitro work cycle studies on the properties of some of the major hindlimb locomotor mouse muscles, and with previously established data in the rat. It is concluded that the mouse shows a consistent and quantifiable gait that would allow incorporation of locomotor assessment into the evaluation of a number of pathophysiological states.

A quantitative study of normal locomotion in the rat

Three variables of locomotion; stride length, stride frequency and velocity have been measured in forty-eight rats. Median values were found to be 11.3 cm, 2.4 Hz and 24.2 cm/sec respectively. The results are assessed both as independent variables and in terms of their interaction. It was found that the two variables used to increase velocity (stride length and stride frequency) were not deployed equally during normal walking velocities (10-50 cm/sec). It is proposed that the study of these three readily quantifiable variables, particularly the relationships between velocity and stride frequency may be useful for the evaluation of locomotion in the assessment of neuropharmacologically active agents.

Gait analysis in a rat model of osteoarthrosis.

Gait analysis has been undertaken in a rat model of osteoarthrosis, induced by intra-articular injection of sodium iodoacetate into the left knee. Two weeks after injection, no disturbances were recorded to the velocity of locomotion, the stride length nor the stride, stance, or swing times. However, clear and consistent reductions in the peak vertical load bearing (Pz) by the affected limb were observed of 22-29% relative to the other limbs, with the right forelimb taking the major share of extra load. This redistribution fitted well with the gait pattern of the rat, allowing Pz redistribution with minimum gait disturbance, and was still present 6 weeks later. These results are discussed in the context of the possible load sensitivity of the damage process to the gait pattern of the rat.

Development and consistency of gait in the mouse.

Mouse models of human disease may display developmental abnormalities or adult onset of the condition. Since many diseases are accompanied by gait disturbances, knowledge of normal gait development in the mouse and its adult characteristics might be valuable as standards against which to appraise disease progression and the efficacy of putative therapies. Assessment of the gait of mice from postnatal day (pnd) 13 to postnatal week (pnw) 80 was undertaken utilising video techniques to examine velocity, stride, stance and swing times and between pnw 29 and 80 using load cells for analysis of the vertical reaction force (P(z)) associated with limb placements. Some adult features are apparent by pnd 13, but in the hindlimb (HL) particularly, the adult pattern of relationships between stride, stance and swing are not established. Adult characteristics of forelimb (FL) deployment develop earlier than those of HL while the systems controlling HL stance develop earlier than those regulating its swing. All the features measured, however, such as the shorter stance and longer swing of FL compared to HL, are established in their adult form by pnd 24 and maintained throughout adult life. In healthy mice at pnw 80, there was no deviation from the adult pattern of gait in which P(z) transmitted via FL exceeds that via HL by around 5%. We did not detect any significant change in any other variable or in their relationships.

Differential fore- and hindpaw force transmission in the walking rat

Previous studies suggest that the stance phase of the rat stride is initiated by a soft contact period when the forepaw may engage in tactile sampling of the terrain. However, no ground reaction force measurements have yet been made during rat locomotion. In the dog and other quadrupeds a brief or nonexistent soft contact phase is observed. Therefore, forces and pressures exerted via fore and hindpaws have been measured in the spontaneously walking rat. These indicate while the hindpaw vertical reaction forces are temporally similar to those in the dog, those transmitted via the forepaw are not. At average walking velocities the forepaw soft contact time is some 4 times longer than that of the hindpaw, with values of 207 +/- 25 ms and 52 +/- 12.2 ms (mean +/- 1 SEM) respectively. These data are consistent with the idea of forepaw useage to provide tactile information of the terrain during a prolonged initial soft contact phase, while the hindpaw transmits most of the early vertical ground reaction forces.

Gait topography in rat locomotion

Gait topography has been quantified and normative data established for free, spontaneous locomotion in rats. The normal walking pattern has been compared for male and female rats and for three rat strains. The normal walking gait was found to be symmetrical, and measures of stride width (SW) and stride length (SL) were consistent, with coefficients of variability ranging between 10 and 21%. A study of gait ontogeny found that for both male and female rats, SL increased as a linear function of body weight, whereas SW increased curvilinearly. The results indicate that repeated measures of gait topography were not subject to interference from habituation. A sex difference in gait ontogeny was observed. The developmental pattern is similar for both sexes, but males increase both SL and SW faster than females. It is proposed that gait topography may yield valuable information in activity studies.

Potentiation of motoneurone excitability by combined administration of 5-HT agonist and TRH analogue

Motoneurone field potentials have been recorded from the lumbar region of the spinal cord, to antidromic stimulation of a ventral root, in rats anaesthetised with urethane. Injection of the thyrotropin releasing hormone (TRH) analogue RX77368 (1mg/kg) plus the 5-hydroxytryptamine (5-HT) receptor agonist 5-methoxy-N, N-dimethyl-tryptamine (5MeODMT 0.4mg/kg) resulted in a potentiation of the increase in amplitude and duration of response, compared to when the drugs were given singly. These results are discussed in the context of possible interactions between 5-HT and TRH systems.

Swing time changes contribute to stride time adjustment in the walking rat.

Locomotor analysis is a useful tool for assessing normal and disturbed brain function. Previous studies have indicated that, during locomotion at walking velocities, the rat adjusts its velocity by changes to stride time and length. The present work has shown that, in the Sheffield strain rat, changes in stride time are achieved by a differential deployment of its two components, stance time and swing times. During slow walking, swing time changes provide minimal contribution to stride time reductions. At above average stride frequencies, however, swing time changes become significant, providing for more than half the reduction over parts of the range.

Gait analysis in the rat as a model for the study of peripheral vascular disease.

A number of problems are associated with investigation of the pathophysiology of peripheral vascular disease (PVD) in humans and unilateral ligation of the common iliac artery in the rat has been extensively used as an experimental model of PVD. However, techniques so far applied to monitor the effects of PVD on muscular function are invasive and difficult to relate to natural locomotion. The present study aimed to investigate gait during spontaneous, unforced locomotion in the animal model. No differences were observed between control and experimental rats in velocity or stride lengths. Although stride time was unchanged, its internal balance was disturbed with reduced stance, prolonged swing, for the ligated limb (LL) relative to the nonligated limb (NLL). Gait symmetry was also affected with NLL strike occurring earlier during LL stance. Analysis of footfall patterns showed a reduction of stance area and pressures exerted via LL relative to NLL. It is concluded that gait and footfall analysis could be useful for assessing limb function under natural exercise conditions.

Development of locomotion in the rat : spatiotemporal footfall patterns

Footfall patterns during locomotor ontogeny have been observed in Wistar rats 10-30 days old. These reveal that, even at 22 days, the paw contacts are both spatially and temporally unlike those of the adult. In the adult there is a precise presentation sequence involving early soft contact of tactile sensitive forepaw parts that may be important in tactile locomotor guidance and which is not fully established even at 22-30 days. The hindpaw contact pattern is also not yet adult-like involving a greater incidence of early toe contact. It is suggested that, only after day 15, when the forelimb is no longer the major weight-bearing limb, can it start to be developed for the fine discriminative touch required for tactile guidance of limb placement. Some further time is necessary for adult patterns to be achieved.