Impact of spasticity in the development of neurological heterotopic ossifications (NHOs) : injection of botulinum toxin in a mouse model developing NHOs.
Dr Marjorie SALGAa, Ms Charlotte DEBAUDb, Mrs Irina KULINAc, Mr Cedryck VAQUETTEd, Mr Jean-Pierre LEVESQUEc, Dr François GENÊTe
a 1 Université Versailles Saint Quentin en Yvelines, END:ICAP U1179 INSERM, UFR des Sciences de la Santé–Simone Veil,, b 1 Université Versailles Saint Quentin en Yvelines, END:ICAP U1179 INSERM, UFR des Sciences de la Santé–Simone Veil, Montigny le Bretonneux, France, c 3 Blood and Bone Diseases Programme, Mater Research Institute, University of Queensland, Woolloongabba, Australia ;4 School of Medicine, University of Queensland, Herston, Australia, d 5 Institute of Health Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Australia, e 1 Université Versailles Saint Quentin en Yvelines, END:ICAP U1179 INSERM, UFR des Sciences de la Santé–Simone Veil, Montigny le Bretonneux, France 2 Department of Physical Medicine and Rehabilitation, Hôpital Raymond Poincaré, APHP, CIC-IT 1429, Garches,
INTRODUCTION: Neurological heterotopic ossifications (NHOs) are bone formations developed around joints following central nervous system lesion. The pathological mechanism remains unknown and there is no therapeutic option to prevent this complication. Several studies have examined the risk factors occurred in the NHO including spasticity. Some see it as a risk factor, others as a result of the formation of the NHO, which would act as an irritating factor. The objective of this work is to define the role of spasticity in the development of NHOs by injecting botulinum toxin into mice producing NHOs after spinal section.
MATERIAL AND METHOD: Thirteen wild mice C57 / BL6 benefited from T7 level of surgical spinal section associated with injections of 12.5 mg of cardiotoxin in the hamstrings to develop HOs. Among them, five mice received an additional injection of botulinum toxin in the ipsilateral hamstring at 20mu.l (1U / 100 g body weight) 4 days before spinal section and 1 per week until sacrifice of the animal (14 days). A micro-computed tomography analysis was used to determine the bone volume (BV) of the HO.
RESULTS: The mice in the 2 groups had 100% of spastic paraparesis and NHO, suggesting that botulinum toxin has no effect on their appearance. The BV average is 7.39 mm3 (+/- 5.79) for the control group and 12.35 mm3 (+/- 10.24) for the botulin toxin group. The statistical analysis shows no significant difference between the 2 groups (Mann Whitney test, p = 0.17).
CONCLUSION: This study failed to show a modulation effect of spasticity on the development of HOs in mouse with spinal cord injury. Further studies with sciatic nerves section have to be realized in order to measure the impact of flaccid paralysis versus that of spastic paralysis in the development of these NHOs.
Keywords : heterotopic ossification; spinal cord injury; spasticity, botulinum toxin