Download Post-stroke spasticity VO script (video 4)

Post-stroke spasticity VO script (video 4)
Narration
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Botox is a unique biological. It has been licensed for a broad range of therapeutic conditions where
over-activity in sensory and/or motor pathways is key to the pathophysiology.
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One of these conditions is spasticity as a result of stroke, which arises from upper motor neuron
lesions that promote motor dysfunction. This can give rise to abnormal muscle tone that can
decrease mobility and impede daily activities. In this video, you will see how BOTOX® acts on motor
neurons to reduce muscle activity in adult patients with wrist and hand spasticity following a stroke.
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Muscle contraction is controlled through the release of the neurotransmitter acetylcholine.
Stimulation of motor neurons causes neurotransmitter-containing vesicles stored in the presynaptic
neuromuscular nerve terminal to dock with the nerve membrane. Docking is facilitated by the
SNARE complex, composed of attachment proteins including SNAP25, which also help the vesicles
fuse with the membrane to release acetylcholine into the synaptic cleft.
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Acetylcholine then travels across the neuromuscular junction where it binds to and activates its
receptors leading to muscle contraction.
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In Post Stroke Spasticity an increase in muscle tone occurs as a result of an increase in the release of
acetylcholine at the neuromuscular junction.
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Botox is injected directly into the affected muscles. Some time after injection, the Botox core 150kilodalton molecule (comprising of a heavy chain and a light chain) dissociates from the surrounding
protective accessory proteins.
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The binding domain of the BOTOX core molecule is the C-terminal portion of the heavy chain, which
interacts with receptors on the motor nerve terminal. The Botox protein then enters the motor
nerve through a process known as receptor mediated endocytosis and is now encapsulated within a
membranous vesicle inside the cell.
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The light chain is now released into the cytoplasm of the nerve terminal.
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The light chain of the BOTOX® core molecule blocks the release of acetylcholine from motor neurons
by cleaving SNAP-25, which is an essential component of the SNARE complex.
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When acetylcholine cannot be released, muscle contraction cannot occur. Intramuscular injection of
Botox at therapeutic doses produces a partial chemical denervation of the muscle, resulting in a
localized reduction in muscle activity.
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Botox inhibits the local release of neurotransmitters at nerve terminals in motor pathways, thereby
preventing overactive muscle contractions. Through this mechanism Botox can help reduce the
burden associated with post stroke spasticity by targeting the motor neurons involved in controlling
muscle tone.
On screen text
Post-stroke Spasticity
Normal Muscle Function
Acetylcholine
SNARE Complex
Receptor
How BOTOX® Works
(botulium toxin type A)
Heavy Chain
Light Chain
Snap-25