Regeneration, Repair, and Developmental NeuroscienceResearch PaperVitamin D3 improves respiratory adjustment to fatigue and H-reflex responses in paraplegic adult rats
Highlights
▶Vitamin D has a powerful effect on axogenesis and functional recovery in a model of SCI. ▶Vitamin D is a potent neuro-regenerative molecule. ▶Vitamin D can be used for improving neuromuscular adaptive mechanisms. ▶Vitamin D is an FDA-approved molecule with very limited side effects. ▶Our promising results pave the way for clinical trials in paraplegic patients.
Section snippets
Animals
Adult female Sprague–Dawley rats (8 week old at the start of the experiment), weighing 300 g (Charles River®, Les Oncins, France), were housed in smooth-bottomed plastic cages at 22 °C with a 12-h light/dark cycle. Food (Purina®, rat chow) and water were available ad libitum. The calcium and vitamin D content in the diet was 9,000 mg/kg and 1,200 IU/kg, respectively. All animals were weighted before each experiment step.
Ethical approval
Anesthesia and surgical procedures were performed according to the French
Vitamin D increases the number of axons crossing the lesion
As shown on Fig. 1A, the mean number of axons in the white matter of the proximal region of the lesion was 567,884±44,949, 2,928.86±556.25, 5,836.50±986.93 and 4,783.28±986.23 for the Control, Vehicle, D50 and D200 groups, respectively. However, the observed trend did not reach statistical significance. Conversely, we observed a statistically significant (P<0.01) increase in axons within the distal area of vitamin D-treated animals: the mean number of axons in the white matter was
Discussion
The present study shows for the first time, in an animal model of spinal cord compression, that vitamin D3 is a potent neuroactive compound that (i) increases the number of axons within the lesion site; (ii) improves respiratory response to electrically-induced muscular fatigue, and (iii) restores H-reflex evoked response.
In a previous study, using a rat model of peripheral nerve transection, we showed that vitamin D2 supplementation induces an increased axon number in both the proximal and the
Acknowledgments
This work was supported by grants from “ALARME” Association, “Demain Debout” Association, “Combattre la Paralysie” Association, Louis D. Foundation (Institut de France), Intermarché “Jean-Pierre et Marie-Thérèse Le Roch” Foundation, Délégation Générale pour l'Armement (DGA), IRME (Institut pour la Recherche sur la Moelle épinière et l'Encéphale), L. Saugstad Foundation, Aix-Marseille University (Université de la Méditerranée - Aix Marseille II) and CNRS (Centre National de la Recherche
References (87)
- et al.
Spinal cord transection-no loss of distal ventral horn neurons
Exp Neurol
(1997) - et al.
Behavioural characterization of vitamin D receptor knockout mice
Behav Brain Res
(2005) - et al.
Evidence that alterations in presynaptic inhibition contribute to segmental hypo- and hyperexcitability after spinal cord injury in man
Electroencephalogr Clin Neurophysiol
(1993) - et al.
Fatigue-induced changes in group IV muscle afferent activity: differences between high- and low-frequency electrically induced fatigues
Brain Res
(1997) - et al.
Decreased dynorphin A (1-17) in the spinal cord of spastic rats after the compressive injury
Brain Res Bull
(2005) - et al.
Transsynaptic degeneration of motoneurones caudal to spinal cord lesions
Brain Res Bull
(1989) - et al.
Stimulation by central command of locomotion, respiration and circulation during exercise
Respir Physiol
(1985) - et al.
Vitamin D, a neuro-immunomodulator: implications for neurodegenerative and autoimmune diseases
Psychoneuroendocrinology
(2009) - et al.
An electrophysiological investigation into the monosynaptic H-reflex in the rat
Brain Res
(1998) - et al.
Effect of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide on spinal motor systems in anesthetized intact and spinalized rats
Eur J Pharmacol
(1996)
Effects of 8-OH-DPAT, a 5-HT1A receptor agonist, and DOI, a 5-HT2A/2C agonist, on monosynaptic transmission in spinalized rats
Brain Res
Serotonergic fiber sprouting to external anal sphincter motoneurons after spinal cord contusion
Exp Neurol
An investigation of possible transynaptic neuronal degeneration in human spinal cord injury
J Neurol Sci
Better functional outcome of compression spinal cord injury in mice is associated with enhanced H-reflex responses
Exp Neurol
Effect of spinal cord injury severity on alterations of the H-reflex
Exp Neurol
Incomplete spinal cord injury: neuronal mechanisms of motor recovery and hyperreflexia
Arch Phys Med Rehabil
The monosynaptic reflex: a tool to investigate motor control in humansInterest and limits
Neurophysiol Clin
Presynaptic selection of afferent inflow in the spinal cord
J Physiol Paris
The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord
Brain Res Bull
Effects of exercise and fetal spinal cord implants on the H-reflex in chronically spinalized adult rats
Brain Res
Levels of gamma-aminobutyric acid in the dorsal grey lumbar spinal cord during the development of experimental spinal spasticity
Life Sci
Vitamin D and ageing: neurological issues
Neuropsychobiology
A sensitive and reliable locomotor rating scale for open field testing in rats
J Neurotrauma
Spasticity in rats with sacral spinal cord injury
J Neurotrauma
25-hydroxycholecalciferol stimulation of muscle metabolism
J Clin Invest
Monosynaptic and oligosynaptic contributions to human ankle jerk and H-reflex
J Neurophysiol
The quadriceps stretch reflex in human spasticity
J Neurol Neurosurg Psychiatry
Does elimination of afferent input modify the changes in rat motoneurone properties that occur following chronic spinal cord transection?
J Physiol
Athletic performance and vitamin D
Med Sci Sports Exerc
Vitamin D2 potentiates axon regeneration
J Neurotrauma
Evident transsynaptic degeneration of motor neurons after spinal cord injury: a study of neuromuscular jitter by axonal microstimulation
Am J Phys Med Rehabil
Corticospinal tract transection prevents operantly conditioned H-reflex increase in rats
Exp Brain Res
Short-Term and medium-term effects of spinal cord tract transections on soleus H-reflex in freely moving rats
J Neurotrauma
Consistent repeated M- and H-Wave recording in the hind limb of rats
Muscle Nerve
Hemodynamic responses to metaboreflex activation: insights from spinal cord-injured humans
Eur J Appl Physiol
Appearance of reciprocal facilitation of ankle extensors from ankle flexors in patients with stroke or spinal cord injury
Brain
The H-reflex in experimental spinal cord trauma
J Neurosurg
The role played by the afferent metabosensitive fibers in neuromuscular adaptive mechanism
Can J Neurol Sci
Respiratory and cardiovascular responses evoked by tibialis anterior muscle afferent fibers in rats
Exp Brain Res
Influence of the position of the upper limb on the excitability of the reflex arc of the soleus muscle
Electromyogr Clin Neurophysiol
Excitability of motor neurones in spinal shock in man
J Neurol Neurosurg Psychiatry
Effects induced in a monosynaptic reflex path by its activation
J Neurophysiol
Reticulospinal inhibition of transmission in reflex pathways
J Physiol
Cited by (27)
Serum vitamin D insufficiency is correlated with quadriceps neuromuscular functions in patients with anterior cruciate ligament injury: A preliminary study
2024, Asia-Pacific Journal of Sports Medicine, Arthroscopy, Rehabilitation and TechnologyMotor and sensitive recovery after injection of a physically cross-linked PNIPAAm-g-PEG hydrogel in rat hemisectioned spinal cord
2020, Materials Science and Engineering CNon-musculoskeletal benefits of vitamin D
2018, Journal of Steroid Biochemistry and Molecular BiologyRestoration of post-activation depression of the H-reflex by treadmill exercise in aged rats
2016, Neurobiology of AgingWherefore Art Thou, O Treatment for Diabetic Neuropathy?
2016, International Review of NeurobiologyCholecalciferol (vitamin D<inf>3</inf>) improves functional recovery when delivered during the acute phase after a spinal cord trauma
2015, Journal of Steroid Biochemistry and Molecular BiologyCitation Excerpt :The adaptive response observed in the VD1 group after extensor digitorum muscle stimulation indicates that administration of cholecalciferol, one day after the spinal injury, allows the recovery of the network involved in respiratory adjustments initiated by thinly myelinated group III and unmyelinated group IV sensitive fibers that inform, throughout the spinal pathway, the medullary center of the muscle contraction rate. Such improvement had been observed previously in rats with a thoracic compression and treated during 12 weeks with cholecalciferol at the dose of 200 IU/kg/day [6]. The improvement observed in the present model of cervical hemisection, that allows the transmission of the sensory messages from the sub- to the supra-lesional spinal cord, may have an anatomical basis, i.e.: axonal regrowth throughout the lesion, myelination of the newly formed axons, synapse development (newly formed contact between subpopulations of neurons) and/or reorganization of segmental, intersegmental and suprasegmental axonal circuitries allowing nerve impulses to bypass the lesion.