cholecalciferol and Spinal-Cord-Injuries

In 2014, a phase II randomised, double blind clinical trial assessing the efficacy of cholecalciferol (vitamin D3) in patients with a cervical trauma will be set up. This trial stems from previous studies showing that vitamin D supplementation improves functional recovery in rat models of peripheral or central nerve injury. In a first series of experiments, we used a rat model of peripheral nerve trauma to demonstrate the therapeutic efficiency of vitamin D. We first demonstrated that ergocalciferol (vitamin D2) increases the number and the diameter of newly formed axons and improves the response of metabosensitive fibers from tibialis muscle, in a model of transected peroneal nerve. Then, we compared vitamin D2 and vitamin D3 and observed that the latter is more efficient. At the dose of 500 IU/kg/day, vitamin D3 induces a dramatic functional recovery. We also demonstrated that vitamin D3 increases the number of preserved or newly formed axons in the proximal end, the mean axon diameter in the distal end, neurite myelination in both the distal and proximal ends as well as the expression of genes involved in axogenesis and myelination. In parallel, we assessed the therapeutic role of vitamin D on the central nervous system. In a first study, using a rat model of spinal cord compression at the T10 thoracic level, we delivered vitamin D3 (cholecalciferol) orally at the dose of 50 IU/kg/day or 200 IU/kg/day. When compared to control animals, vitamin D-treated rats displayed, three months after injury, a significant improvement of ventilatory frequency and a reduction of H reflex indicating functional improvements at three months post-injury. In a second study, we used a rat model of cervical hemisection (C2) with a higher dose of oral vitamin D3 (500 IU/kg/day) delivered weekly, during 12 weeks. We observed an improved locomotor recovery, a reduced spasticity and a significantly higher rate of axons crossing the lesion site in treated animals. However, it must be pointed out that the functional improvement is reduced when vitamin D is provided one week after the trauma.

Topics: Animals; Axons; Axotomy; Cervical Vertebrae; Cholecalciferol; Demyelinating Diseases; Drug Evaluation, Preclinical; Ergocalciferols; Gene Expression Regulation; Humans; Muscle, Skeletal; Nerve Fibers, Myelinated; Nerve Regeneration; Neuroprotective Agents; Peroneal Nerve; Rats; Spinal Cord Injuries; Vitamin D

Vitamin D insufficiency, a vitamin D status or serum 25(OH)D concentration of ≤75 nmol/L, is highly prevalent in individuals with a spinal cord injury (SCI). Vitamin D is important for the functioning of the musculoskeletal, immune and respiratory systems, which are relevant determinants of secondary health conditions in SCI. An insufficiency should be treated with vitamin D supplementation. However, there is a lack of evidence regarding the optimal dosage and duration of vitamin D supplementation for individualised and long-term management of the vitamin D status in the context of SCI. This paper presents the protocol for the vitamin D supplementation in chronic spinal cord injury (VitD-SCI) trial that aims to investigate the effect of a 12-month intake of vitamin D supplementation on vitamin D status as well as on several secondary parameters among individuals with a chronic SCI.. The VitD-SCI trial is a randomised, placebo-controlled, double-blinded, parallel-group, superiority trial, conducted at the Swiss Paraplegic Centre. A total of 45 participants living with an SCI for at least 3 years (chronic SCI) and a vitamin D insufficiency at the first study visit, will be randomly assigned to one of three intervention groups. Participants receive either a monthly dosage of 24 000 IU or 48 000 IU vitamin D or a placebo for 12 months. Measurements taking place every 3 months include the assessment of vitamin D status (primary outcome) as well as bone mineral density, handgrip strength, fatigue, mood, pain and pressure injuries (secondary outcomes). Safety and tolerance of vitamin D supplementation will also be evaluated.. The Swiss Ethics Committee for Northwest/Central Switzerland (EKNZ, 2020-01493) and the Swiss Agency for Therapeutic Products (Swissmedic, 2020DR3150) approved this study. Findings will be disseminated through peer-reviewed publications.. NCT04652544 and SNCTP000004032.

Topics: Cholecalciferol; Dietary Supplements; Hand Strength; Humans; Randomized Controlled Trials as Topic; Spinal Cord Injuries; Vitamin D; Vitamin D Deficiency

Demyelination due to oligodendrocytes loss occurs after traumatic spinal cord injury (TSCI). Several studies have suggested the therapeutic potential of vitamin D (VitD) in demyelinating diseases. However, experimental evidence in the context of TSCI is limited, particularly in the presence of prior VitD-deficiency. In the present study, a contusion and a transection TSCI rat model were used, representing mild and severe injury, respectively. Motor recovery was assessed in rats with normal VitD level or with VitD-deficiency after 8 weeks' treatment post-TSCI (Cholecalciferol, 500 IU/kg/day). The impact on myelin integrity was examined by transmission electron microscopy and studied

Topics: Animals; Cell Differentiation; Cholecalciferol; Myelin Sheath; Oligodendrocyte Precursor Cells; Oligodendroglia; Rats; Remyelination; Spinal Cord; Spinal Cord Injuries; Vitamin D

Topics: Adolescent; Adult; Athletes; Athletic Performance; Canada; Cholecalciferol; Dietary Supplements; Female; Hand Strength; Humans; Male; Middle Aged; Spinal Cord Injuries; Sports for Persons with Disabilities; United States; Vitamin D; Vitamin D Deficiency; Wheelchairs; Young Adult

In a previous study, based on a rat model of thoracic spinal cord compression, we demonstrated that cholecalciferol (Vitamin D3), delivered at the dose of 200 IU/kg/day, significantly improved ventilatory frequency and spasticity. In order to confirm the restorative potential of vitamin D, we performed a new study, using a rat model of left cervical hemisection (C2). From Day 1 or Day 7, animals received, during three months, a weekly oral bolus of either cholecalciferol, at the dose of 500 IU/kg/day, or vehicle, namely triglycerides. Rats were assessed every month, using a ladder test for sensori-locomotor ability and neuromuscular capacity. Three months after injury, H-reflex was recorded from left extensor digitorum muscle in order to measure the reflexivity of the sub-lesional region. Ventilatory frequency was also monitored during an electrically induced muscle fatigue of the hindlimb known to enhance muscle metaboreflex and increase respiratory rate. After recording the phrenic nerve activity, ipsilateral to the lesion, during spontaneous breathing, animals were artificially ventilated while paralyzed with a neuromuscular blocking agent and then the brainstem respiratory centres were provoked to maximal output by temporarily stopping the ventilator. Spinal cords were immunostained with an anti-neurofilament antibody to evaluate axon numbers. We show here that vitamin D-treated animals display i) an enhanced locomotor activity, ii) an improved breathing when hindlimb muscle was electrically stimulated to induce fatigue, iii) an H-reflex depression similar to control animals, iv) a phrenic nerve activity response to a temporary asphyxial stress and v) a non significant decreased number of axons in the proximal stump when compared with the Sham group. This new set of data confirms that vitamin D is a potent molecule that could be tested in clinical trials assessing functional recovery in para-/tetra-plegic patients, shortly after a trauma.

Topics: Animals; Cholecalciferol; Humans; Locomotion; Male; Muscle Spasticity; Random Allocation; Rats; Rats, Sprague-Dawley; Respiration; Spinal Cord Injuries; Thoracic Vertebrae