This study demonstrates a relationship between inflammation/ROS and arterial calcification in CKD and contributes to understanding of the complex pathways that mediate arterial calcification in CKD patients.

Dopamine (DA) is well-recognized for its determinant role in the modulation of various brain functions. DA was also found in in vitro isolated invertebrate preparations to activate per se the central pattern generator for locomotion. However, it is less clear whether such a role as an activator of central neural circuitries exists in vertebrate species. Here, we studied in vivo the effects induced by selective DA receptor agonists and antagonists on hindlimb movement generation in mice completely spinal cord-transected (Tx) at the low-thoracic level (Th9/10). Administration of D1/D5 receptor agonists (0.5-2.5 mg kg −1 , i.p.) was found to acutely elicit rhythmic locomotor-like movements (LMs) and non-locomotor movements (NLMs) in untrained and non-sensory stimulated animals. Comparable effects were found in mice lacking the D5 receptor (D5KO) whereas D1/D5 receptor antagonist-pretreated animals (wild-type or D5KO) failed to display D1/D5 agonist-induced LMs. In contrast, administration of broad spectrum or selective D2, D3 or D4 agonists consistently failed to elicit significant hindlimb movements. Overall, the results clearly show in mice the existence of a role for D1 receptors in spinal network activation and corresponding rhythmic movement generation.

Study design: To compare results obtained with a variety of locomotor rating scales in Th9/10 spinal cord transected (Tx) mice. Objectives: To assess spontaneous recovery with a variety of rating scales to find the most sensitive methods for assessing recovery levels in Tx mice and differences associated with gender and condition. Setting: Laval University Medical Center, Neuroscience Unit & Laval University, Department of Anatomy and Physiology, Quebec City, Quebec, Canada. Methods: Scales including the Basso, Beattie and Bresnahan (BBB), the Basso Mouse Score (BMS), the Antri, Orsal and Barthe (AOB), the Motor Function Score (MFS) and the Averaged Combined Score (ACOS) were used to assess, in open-field and treadmill conditions, spontaneous locomotor recovery in male and female Tx mice. Results: The ACOS scale revealed a progressive increase of spontaneous recovery during 5-weeks post-Tx. The other methods detected a progressive increase for the first 2-3 weeks postTx without any significant progress in weeks 4 and 5. Generally, scores obtained with each method were nonsignificantly different between males and females or between open-field and treadmill conditions. Conclusion: These results further confirm the existence of a limited but significant increase of locomotor function recovery, occurring without intervention, in Tx animals. Although each method could detect small levels of recovery, the ACOS method was discriminative enough to detect progressive changes up to 5 weeks post-Tx. In conclusion, the ACOS rating scale was the most discriminative method for assessing the spontaneous return of hindlimb movements found in Tx mice, both in open-field and treadmill conditions.

Reorganization and plasticity after spinal cord injury have been recently shown to take place in sublesional neuronal networks, but the possibility of strain-dependent changes at that level has never been explored. The authors studied the spontaneous return of hindlimb movement in low-thoracic spinal cord transected (Tx) mice from 3 commonly used strains. Without intervention, most CD1, C57BL/6, and BALB/c mice displayed some hindlimb movement recovery after Tx. Although all assessment methods unanimously reported that CD1 displayed higher recovery levels than did the C57BL/6 and BALB/c, higher scores were generally found with the Antri-Orsal-Barthe (M. Antri, D. Orsal, & J. Y. Barthe, 2002) and the Average Combined Score (P. A. Guertin, 2005a) methods. Such spontaneous recovery in low-thoracic Tx mice is likely the result of neuronal plasticity at the lumbosacral spinal cord level, suggesting that these sublesional changes are strain dependent.

This study indicate that smooth muscle cells differentiation to osteoblast-like cells and the associated media remodeling, which includes disruption of elastic lamellas and deposition of collagen are, at least in part, associated with the increased arterial stiffness observed in CKD rats with vascular calcification.