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Proc Natl Acad Sci U S A ; 109(23): 9155-60, 2012 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-22615373

RESUMO

Physical and chemical constraints imposed by the periinfarct glial scar may contribute to the limited clinical improvement often observed after ischemic brain injury. To investigate the role of some of these mediators in outcome from cerebral ischemia, we treated rats with the growth-inhibitory chondroitin sulfate proteoglycan neurocan, the growth-stimulating heparan sulfate proteoglycan glypican, or the chondroitin sulfate proteoglycan-degrading enzyme chondroitinase ABC. Neurocan, glypican, or chondroitinase ABC was infused directly into the infarct cavity for 7 d, beginning 7 d after middle cerebral artery occlusion. Glypican and chondroitinase ABC reduced glial fibrillary acidic protein immunoreactivity and increased microtubule-associated protein-2 immunoreactivity in the periinfarct region, and glypican- and chondroitinase ABC-treated rats showed behavioral improvement compared with neurocan- or saline-treated rats. Glypican and chondroitinase ABC also increased neurite extension in cortical neuron cultures. Glypican increased fibroblast growth factor-2 expression and chondroitinase ABC increased brain-derived neurotrophic factor expression in these cultures, whereas no such effects were seen following neurocan treatment. Thus, treatment with glypican or enzymatic disruption of neurocan with chondroitinase ABC improves gross anatomical, histological, and functional outcome in the chronic phase of experimental stroke in rats. Changes in growth factor expression and neuritogenesis may help to mediate these effects.


Assuntos
Condroitina ABC Liase/farmacologia , Glipicanas/farmacologia , Neurocam/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Condroitina ABC Liase/administração & dosagem , Condroitina ABC Liase/uso terapêutico , Fator 2 de Crescimento de Fibroblastos/metabolismo , Proteína Glial Fibrilar Ácida/imunologia , Glipicanas/administração & dosagem , Glipicanas/uso terapêutico , Imuno-Histoquímica , Infusões Intra-Arteriais , Proteínas Associadas aos Microtúbulos/imunologia , Neuritos/efeitos dos fármacos , Neurocam/administração & dosagem , Neurocam/uso terapêutico , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Acidente Vascular Cerebral/enzimologia
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