Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats

Justin J. Hill, Kunlin Jin, Xiao Ou Mao, Lin Xie, David A. Greenberg

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

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 proteoglycandegrading 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.

Original languageEnglish (US)
Pages (from-to)9155-9160
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number23
DOIs
StatePublished - Jun 5 2012
Externally publishedYes

Fingerprint

Glypicans
Chondroitin ABC Lyase
Heparan Sulfate Proteoglycans
Neurocan
Stroke
Chondroitin Sulfate Proteoglycans
Microtubule-Associated Proteins
Chondroitin Sulfates
Middle Cerebral Artery Infarction
Glial Fibrillary Acidic Protein
Brain-Derived Neurotrophic Factor
Fibroblast Growth Factor 2
Neurites
Growth
Brain Ischemia
Neuroglia
Brain Injuries
Cicatrix
Intercellular Signaling Peptides and Proteins
Neurons

Keywords

  • Astrocyte
  • Astrogliosis
  • Glia

ASJC Scopus subject areas

  • General

Cite this

Intracerebral chondroitinase ABC and heparan sulfate proteoglycan glypican improve outcome from chronic stroke in rats. / Hill, Justin J.; Jin, Kunlin; Mao, Xiao Ou; Xie, Lin; Greenberg, David A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 23, 05.06.2012, p. 9155-9160.

Research output: Contribution to journalArticle

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