Abstract
Intravenous brain-derived neurotrophic factor (BDNF) causes a 65-70% reduction in stroke volume in rats with the middle cerebral artery occlusion (MCAO), provided the BDNF is conjugated to a blood-brain barrier (BBB) molecular Trojan horse. The latter may be a peptidomimetic monoclonal antibody (MAb) to the transferrin receptor. The present studies determine whether the effects on stroke volume correlate with an improvement in neuro-behavior using the rotarod test. The rotarod latency was >200 s at 16 RPM in all rats pre-MCAO. The latency was 30+/-7 s and 103+/-9 s at 24 h post-MCAO in the animals treated with BDNF alone and the BDNF-MAb conjugate, respectively. These studies show that when BDNF is formulated to enable transport across the BBB, the intravenous administration of the neurotrophin results in a reduction in stroke volume that is associated with a parallel improvement in functional outcome.
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacokinetics
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Antibodies, Monoclonal / therapeutic use
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Blood-Brain Barrier / drug effects*
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Blood-Brain Barrier / metabolism
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Brain-Derived Neurotrophic Factor / metabolism
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Brain-Derived Neurotrophic Factor / pharmacokinetics*
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Brain-Derived Neurotrophic Factor / therapeutic use
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Disease Models, Animal
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Infarction, Middle Cerebral Artery / drug therapy*
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Infarction, Middle Cerebral Artery / metabolism
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Infarction, Middle Cerebral Artery / physiopathology
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Injections, Intravenous
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Male
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Motor Activity / drug effects
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Motor Activity / physiology
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Motor Cortex / drug effects
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Motor Cortex / metabolism
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Motor Cortex / physiopathology
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Movement Disorders / drug therapy*
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Movement Disorders / etiology
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Movement Disorders / physiopathology
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Paresis / drug therapy
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Paresis / etiology
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Paresis / physiopathology
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Rats
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Rats, Sprague-Dawley
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Reaction Time / drug effects
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Reaction Time / physiology
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Recovery of Function / drug effects*
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Recovery of Function / physiology
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Stroke / drug therapy*
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Stroke / metabolism
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Stroke / physiopathology
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Treatment Outcome
Substances
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Antibodies, Monoclonal
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Brain-Derived Neurotrophic Factor