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Science ; 360(6384): 50-57, 2018 04 06.
Article in English | MEDLINE | ID: mdl-29622647

ABSTRACT

Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization. Edonerpic bound to collapsin-response-mediator-protein 2 (CRMP2) and failed to augment recovery in CRMP2-deficient mice. Edonerpic maleate enhanced motor function recovery from internal capsule hemorrhage in nonhuman primates. Thus, edonerpic maleate, a neural plasticity enhancer, could be a clinically potent small compound with which to accelerate rehabilitation after brain damage.


Subject(s)
Brain Injuries/drug therapy , Intercellular Signaling Peptides and Proteins/metabolism , Maleates/metabolism , Maleates/pharmacology , Motor Cortex/drug effects , Nerve Tissue Proteins/metabolism , Neuroprotection , Recovery of Function/drug effects , Thiophenes/metabolism , Thiophenes/pharmacology , Animals , Male , Maleates/therapeutic use , Mice , Mice, Knockout , Mice, Mutant Strains , Motor Cortex/injuries , Motor Cortex/physiopathology , Neuronal Plasticity/drug effects , Quality of Life , Receptors, AMPA/metabolism , Stroke/complications , Stroke/drug therapy , Thiophenes/therapeutic use
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