A novel protocol for the quantification of temporal and postural gait parameters of rats and humans

Madete, June 2011. A novel protocol for the quantification of temporal and postural gait parameters of rats and humans. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Animal models have been used for many years to generalise the human condition of various neurological diseases. It is important that the behavioural attributes from the animal model directly correlate with those found in the human pathology. Motion analysis (MA) techniques provide a platform for direct correlation analysis between the two species, which is an important step for translational medicine. A novel three dimensional (3D) MA protocol was developed to investigate temporal and postural gait variables in both rats and humans. Gait studies involving rats are mainly based on movement scores or descriptive approaches to discerning differences in behaviour or function. Therefore, a protocol utilising a quantitative 3DMA technique during gait was developed. Data was acquired to describe function and behavioural attributes in animal models of Parkinson‟s disease (PD) and stroke in terms of temporal gait and postural adjustments and on a healthy cohort of humans. The study explored the practicality of the developed protocol to investigate the effects of unilateral dopamine depletion on rat locomotion while walking on beams of varying widths (wide, narrow and graduated). Temporal and postural gait parameters of ten male Lister Hooded rats (five controls (CNL) and five hemi-parkinsonian (PNL)) were observed using passive markers placed in locations that were representative of their four limbs and their body axis. Significant differences (p<0.05) were found between the PNL and CNL rats for speed along the wide beam and stride lengths for the left (impaired) fore-limb; on the narrow beam and the wide beam and for the left (impaired) hind limb on the graduated beam. The PD rats moved on the wide beam with a significantly greater roll range of motion (ROM) coupled with a positively biased roll kinematic waveform during one gait cycle. Whilst walking on the narrow beam, they displayed an increased use of the ledge and placed their tail towards the right. The results demonstrate that marker-based MA can provide an effective and simple approach to quantifying temporal gait parameters for rat models of PD. They also reveal how the width of the path affects the locomotion in both experimental cohorts. ii The novel protocol was applied to investigate the effects of Middle Cerebral Artery Occlusion (MCAO) and graft on rat locomotion while walking on a wide beam. The data collection was carried out before and after surgery to investigate temporal and postural gait parameters of 50 male Wister rats. Significant differences (p<0.05) were found between the control and MCAO rats for roll ROM coupled with a positively biased roll kinematic waveform during one gait cycle. Using the data collected, a classification tool based around the Dempster-Shafer theory enabled the objective classification of the rat cohorts into a MCAO group, a control group and a graft group. The roll ROM and swing time data were transformed into a set of belief values that the animals had graft, lesion or normal gait. The belief values were then represented on a simplex plot, which enables the final classification of a rat, and the level of benefit achieved by lesion or graft surgery to be visualised. The tool was able to classify rats with an accuracy of between 81% and 94.84% accuracy. The tool also indicated that swing time and roll were the most influential variables in distinguishing differences in gait after MCAO lesion and graft. Further work is required on the graft data as some inconsistencies were found, but the classification allowed better comparisons between groups than just using ANOVA alone by taking this level of uncertainty and producing a clear comparison between the cohorts. Initial studies have demonstrated a practical and visual approach that can discriminate between gait function in the rat model. Therefore to achieve the aim of the thesis, a cohort of healthy humans were tested to replicate the data collection and processing protocols developed for animal MA. The marker based protocol was carried out to investigate temporal and postural gait parameters of 10 healthy human subjects (five male: five female). The data collected compared well with published data for normal human gait therefore validating the human based protocol. The results identified variables that were easily correlated with rat data. Similarities in body orientation patterns were recorded and discussed. In conclusion, a novel protocol was developed that allowed a simple, non-invasive, practical, and sensitive approach to over ground gait data acquisition for the rat models and a healthy human cohort. Further work that would involve patients with neurological disease will enable the full validation of the protocol. This is turn would provide answers to the argument: „Is the use of animal models of the disease effective approach for clinical research?‟

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Engineering
Uncontrolled Keywords:	Rat models; Transgenic models; Gait; Posture; Parkinsons Disease; Stroke; Motion analysis
Date of First Compliant Deposit:	30 March 2016
Last Modified:	19 Mar 2016 22:21
URI:	https://orca.cardiff.ac.uk/id/eprint/13152

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