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

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 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.

• Authors: Justin J Hill, Kunlin Jin, Xiao Ou Mao, Lin Xie, David A Greenberg
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 109 Issue 23 Pg. 9155-60 (Jun 05 2012) ISSN: 1091-6490 [Electronic] United States
• PMID: 22615373 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Brain-Derived Neurotrophic Factor
• Glial Fibrillary Acidic Protein
• Glypicans
• MAP2 protein, rat
• Microtubule-Associated Proteins
• Neurocan
• Fibroblast Growth Factor 2
• Chondroitin ABC Lyase

Topics

• Animals
• Blotting, Western
• Brain-Derived Neurotrophic Factor (metabolism)
• Chondroitin ABC Lyase (administration & dosage, pharmacology, therapeutic use)
• Fibroblast Growth Factor 2 (metabolism)
• Glial Fibrillary Acidic Protein (immunology)
• Glypicans (administration & dosage, pharmacology, therapeutic use)
• Immunohistochemistry
• Infusions, Intra-Arterial
• Microtubule-Associated Proteins (immunology)
• Neurites (drug effects)
• Neurocan (administration & dosage, pharmacology, therapeutic use)
• Psychomotor Performance (drug effects)
• Rats
• Rats, Sprague-Dawley
• Stroke (drug therapy, enzymology)