Publication Date:
2015-04-28
Description:
Background and Purpose— Previous studies reported that Tat-NR2B9c, a peptide disrupting the N -methyl- d -aspartate receptor–postsynaptic density protein-95 interaction, reduced ischemic damage in the acute phase after stroke. However, its effect in the subacute phase is unknown. The aim of this study is to determine whether disrupting the N -methyl- d -aspartate receptor–postsynaptic density protein-95 interaction in the subacute phase promotes recovery after stroke. Methods— Studies were performed on Sprague-Dawley rats or nNOS –/– mice, and experimental ischemic stroke was induced by middle cerebral artery occlusion. Animals were treated with drugs starting at day 4 after ischemia. Sensorimotor functions and spatial learning and memory ability were assessed after drug treatment. Then, rats were euthanized for morphological observation and biochemical tests. Results— Disrupting the N -methyl- d -aspartate receptor–postsynaptic density protein-95 interaction with Tat-HA-NR2B9c significantly ameliorated the ischemia-induced impairments of spatial memory and sensorimotor functions in rats during subacute stage but did not improve stroke outcome in nNOS –/– mice. Consistent with the functional recovery, Tat-HA-NR2B9c substantially increased neurogenesis in the dentate gyrus and dendritic spine density of mature neurons in the motor cortex of rats, meanwhile, reversed the ischemia-induced formation of S -nitrosylation-cyclin-dependent kinase 5 and increased cyclin-dependent kinase 5 activity in ipsilateral hippocampus. However, directly blocking N -methyl- d -aspartate receptors with MK-801 or Ro 25-6981 did not show the beneficial effects above. Conclusions— Dissociating N -methyl- d -aspartate receptor–postsynaptic density protein-95 coupling by Tat-HA-NR2B9c in the subacute phase after stroke promotes functional recovery, probably because of that it increases neurogenesis and dendritic spine density of mature neurons via regulating cyclin-dependent kinase 5 in the ischemic brain.
Keywords:
Animal models of human disease, Neuroprotectors
Print ISSN:
0039-2499
Electronic ISSN:
1524-4628
Topics:
Medicine
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