Rolipram promotes functional recovery after contusive thoracic spinal cord injury in rats.

Numerous animal model studies in the past decade have demonstrated that pharmacological elevation of cyclic AMP (cAMP) alone, or in combination with other treatments, can promote axonal regeneration after spinal cord injury. Elevation of cAMP via the phosphodiesterase 4 (PDE4) inhibitor, rolipram, decreases neuronal sensitivity to myelin inhibitors, increases growth potential and is neuroprotective. Rolipram's ability to cross the blood-brain barrier makes it a practical and promising treatment for CNS regeneration. However, several studies have questioned the efficacy of rolipram when given alone. The purpose of this investigation was to determine the effects of continuous administration of rolipram, given alone for 2 weeks, following a moderate T10 contusion injury in rat. Functional recovery was evaluated using the 21-point Basso, Beattie and Bresnahan (BBB) locomotor recovery scale and the beam walk. We used three-dimensional (3D) instrumented gait analysis to allow detailed assessment and quantification of hindlimb motion. The amount of the damaged tissue and spared white matter was estimated stereologically. Our results show that administration of rolipram following acute spinal cord contusion results in improved motor performance at each time-point. Dynamic assessment of foot motion during treadmill walking revealed a significantly decreased external rotation during the entire step cycle after 8 weeks in rolipram-treated animals. Stereological analysis revealed no significant differences in lesion volume and length. By contrast, spared white matter was significantly higher in the group treated with rolipram. Our results suggest a therapeutic role for rolipram delivered alone following acute SCI.

The effect of gait speed on three-dimensional analysis of hindlimb kinematics during treadmill locomotion in rats.

The two-dimensional (2D) kinematic approach is by far the most popular technique in rat gait analysis. This is a simple inexpensive procedure, which requires only one camera to record the movement. However, maximal precision and accuracy of the kinematic values are expected when the experimental protocol includes a three-dimensional (3D) motion analysis methodology. Locomotor speed is a basic kinematic parameter that is often neglected in most studies of movement disorders and neurological diseases. Because locomotor speed can act as confounder for the interpretation of the obtained results we also focused our attention on the relation between speed and 3D hindlimb kinematics. Our experimental set-up consisted of a motion capture system with four CMOS cameras which allowed a non-invasive estimation of the instantaneous position of color markers in a 3D measurement volume. Data were recorded while rats walked at different treadmill speeds (30 vs 60 cm/s). For the first time we reported detailed kinematic data for the sagittal, coronal and transverse plane during treadmill locomotion in rats. Despite the overall time course patterns of the curves were identical, we found significant differences between values of joint angular motion at 30 and 60 cm/s at selected points of the step cycle. The adaptation to higher treadmill walking included greater joint angular excursions. The present report highlights the importance of walking speed when evaluating rat hindlimb kinematics during gait. Hopefully, this study will be useful in experimental data assessment when multiple gait abnormalities are expected to occur in all planes of motion.

Automatic histogram threshold using fuzzy measures.

In this paper, an automatic histogram threshold approach based on a fuzziness measure is presented. This work is an improvement of an existing method. Using fuzzy logic concepts, the problems involved in finding the minimum of a criterion function are avoided. Similarity between gray levels is the key to find an optimal threshold. Two initial regions of gray levels, located at the boundaries of the histogram, are defined. Then, using an index of fuzziness, a similarity process is started to find the threshold point. A significant contrast between objects and background is assumed. Previous histogram equalization is used in small contrast images. No prior knowledge of the image is required.

Methylprednisolone fails to improve functional and histological outcome following spinal cord injury in rats.

Currently, methylprednisolone sodium succinate (MPSS) is the standard treatment following acute spinal cord injury (SCI) as a consequence of the results obtained from the National Acute Spinal Cord Injury Studies. However, many have questioned the efficacy of MPSS because of its marginal effects. Additionally there has been criticism of both study design and statistical interpretation. The functional consequences of experimental SCI have been assessed in many ways. The purpose of this investigation was to determine the effects of MPSS vs. saline solution (SS) following moderate T10 contusion injury in rat. Functional recovery was evaluated using the 21-point Basso, Beattie and Bresnahan (BBB) locomotor recovery scale, the inclined plane, the beam walk, footprint analysis and the horizontal ladder. To optimize the precision and accuracy of functional results we examined the locomotion on a treadmill using three-dimensional (3D) analysis. Stereology was used to estimate the amount of damaged tissue. The results of the traditional functional methods showed that administration of the NASCIS dosage of MPSS following acute spinal cord contusion did not lead to any significant differences in the functional recovery of MPSS- vs. SS-treated animals. More importantly, the results of the 3D kinematic showed that the MPSS administration did not affect the flexion/extension of the hip, knee and ankle joints during the step cycle. Finally, stereological results revealed no statistically significant differences between the two experimental groups. Altogether, our results support data previously reported by several authors, suggesting that MPSS does not lead to improved functional outcome following experimental acute SCI.

A comparison of two-dimensional and three-dimensional techniques for the determination of hindlimb kinematics during treadmill locomotion in rats following spinal cord injury.

Of all the detrimental effects of spinal cord injury (SCI), one of the most devastating effects is the disruption of the ability to walk. Therefore, much effort has been focused on developing several methods to document the recovery of locomotor function after experimental SCI. Computerized rat gait analysis is becoming increasingly popular in the SCI research community. The two-dimensional (2D) kinematic approach is by far the most popular technique in rat gait analysis. This is a simple inexpensive procedure, which requires only one camera to record the movement. Our study included an examination of locomotion on a treadmill using 2D and three-dimensional (3D) analysis, in neurologically intact animals and following moderate T9 contusion injury. Despite the overall time course patterns of the curves were identical, we found significant differences between values of the 2D and 3D joint angular motion. In conclusion, maximal precision and accuracy of the kinematic values are expected when the experimental protocol includes a 3D motion analysis methodology. Moreover, a 2D method cannot be used to determine the external or internal rotations of the foot because this movement occurs in the transverse plane.

A comparison analysis of hindlimb kinematics during overground and treadmill locomotion in rats.

The convenience of the motor-driven treadmill makes it an attractive instrument for investigating rat locomotion. However, no data are available to indicate whether hindlimb treadmill kinematic findings may be compared or generalized to overground locomotion. In this investigation, we compared overground and treadmill locomotion for differences in the two-dimensional angular kinematics and temporal and spatial measurements for the hindlimb. Ten female rats were evaluated at the same speed for natural overground and treadmill walking. The walking velocity, swing duration and stride length were statistically indistinguishable between the two testing conditions. Significant differences were found between overground and treadmill locomotion for step cycle duration and stance phase duration parameters. During the stance phase of walking, the angular movement of the hip, knee and ankle joints were significantly different in the two conditions, with greater flexion occurring on the overground. Despite this, the sagittal joint movements of the hindlimb were similar between the two walking conditions, with only three parameters being significantly different in the swing. Hip height and angle-angle cyclograms were also only found to display subtle differences. This study suggests that reliable kinematic measurements can be obtained from the treadmill gait analysis in rats.

Effect of skin movement on the analysis of hindlimb kinematics during treadmill locomotion in rats.

In rat gait kinematics, the method most frequently used for measuring hindlimb movement involves placing markers on the skin surface overlying the joints being analyzed. Soft tissue movement around the knee joint has been considered the principle source of error when estimating hindlimb joint kinematics in rodents. However, the motion of knee marker was never quantified, nor the different variations in joint angle associated with this gait analysis system. The purpose of this study was two-fold. The first purpose was to expand upon the limited pool of information describing the effect of soft tissue movement over the knee upon the angular positions of the hip, knee and ankle of rats during treadmill locomotion. Secondly, it was a goal of this study to document the magnitude of the skin displacement when using markers that were attached superficially to the knee joint. This was examined by comparing the hindlimb kinematics in sagittal plane during treadmill locomotion determined from the marker attached to the knee and when the knee position was determined indirectly by computer analysis. Results showed that there is a considerable skin movement artefact which propagates to knee joint position and hindlimb kinematics estimates. It was concluded that these large errors can decrease data reliability in the research of rat gait analysis.