Nimodipine prevents the development of spasticity after spinal cord injury

Abstract

Spasticity, one of the most frequent comorbidities of spinal cord injury (SCI), disrupts motor recovery and quality of life. Despite major progress in neurorehabilitative and pharmacological approaches, no curative treatment for spasticity exists. Here, we show in a mouse model of chronic SCI that treatment with nimodipine -an FDA-approved L-type calcium channel blocker -starting in the acute phase of SCI completely prevents the development of spasticity measured as increased muscle tone and spontaneous spasms. The aberrant muscle activities are permanently blocked even after termination of the treatment. Constitutive and conditional silencing in neuronal subtypes of Ca V 1.3 channels shows that preventive effect of nimodipine on spasticity after SCI is mediated by the neuronal Ca V 1.3 channels. This study identifies a potentially curative treatment protocol with a specific target for the prevention of spasticity after SCI.

<p>Botulinum Toxin Type A Possibly Affects Ca_v3.2 Calcium Channel Subunit in Rats with Spinal Cord Injury-Induced Muscle Spasticity</p>

“…24 Muscle spasm will be developed after SCI induction. 16 Contusion was induced on laminectomized animals and muscle spasticity was determined by evaluating muscle tone and muscle spasm according to the Ashworth and spasm-frequency scales. 25 Post-operative care was performed including manually assisted extrusion and analgesia.…”

“…15 Calcium channel blockers are thought effective to prevent muscle spasticity. 16 Botulinum toxins type A (BoT-A) is produced from Clostridium botulinum type A and its main function is the cleavage of neuronal synaptosomal-associated protein of 25 kDa (SNAP-25), a protein involved in vesicular membrane fusion with neuronal plasma membrane. 17,18 BoT-A is intended for intramuscular, intradetrusor and intradermal use, and has been increasingly used in clinical care for many neural disorders that include spasticity, 19 and other abnormal movement diseases.…”

“…22 The prevention of the activity of calcium channel can reduce spasticity. 16 BoT-A may prevent SCI-induced muscle spasticity as a kind of calcium channel blocker or by affecting calcium release. In the present work, muscle spasticity was characterized by measuring swimming activities in spinal cord-injured rats injected with different doses of BoT-A and the related molecules Ca v 3.2 subunit (which underlies the functional T-type calcium channel 23 ) and its mutant were measured.…”

Enhancement of nerve regeneration with nimodipine treatment after sciatic nerve injury

“…The FDA-approved medication nimodipine is an Ltype calcium channel antagonist that may cross the blood-brain barrier and alleviate intracellular calcium excess after nerve injuries [12,13]. An increasing amount of research suggests that nimodipine has neuroprotective benefits in a variety of neurological illnesses, including stroke, multiple sclerosis, and Alzheimer's disease [14][15][16].…”

Management of spasticity and psychological symptoms through hypnosis in stroke survivors

“…7 Spasticity is the development of rigid muscle tone following a stroke that involves spontaneous spasms. 8 This motor neuron syndrome creates barriers to optimal functional mobility that impairs the quality of life. 9 In addition to physiological symptoms, stroke survivors also face psychological issues.…”