Intracerebral Chondroitinase ABC and Heparan Sulfate Proteoglycan Glypican Improve Outcome from Chronic Stroke in Rats

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 May 23

PMID 22615373

Citations 47

Authors

Justin J Hill

Kunlin Jin

Xiao Ou Mao

Lin Xie

David A Greenberg

Affiliations

Soon will be listed here.

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.

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References

Coles C, Shen Y, Tenney A, Siebold C, Sutton G, Lu W . Proteoglycan-specific molecular switch for RPTPσ clustering and neuronal extension. Science. 2011; 332(6028):484-8. PMC: 3154093. DOI: 10.1126/science.1200840. View

Walicke P, Cowan W, Ueno N, Baird A, Guillemin R . Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. Proc Natl Acad Sci U S A. 1986; 83(9):3012-6. PMC: 323437. DOI: 10.1073/pnas.83.9.3012. View

Jain A, McKeon R, Brady-Kalnay S, Bellamkonda R . Sustained delivery of activated Rho GTPases and BDNF promotes axon growth in CSPG-rich regions following spinal cord injury. PLoS One. 2011; 6(1):e16135. PMC: 3026041. DOI: 10.1371/journal.pone.0016135. View

Smit M, Leng J, Klemke R . Assay for neurite outgrowth quantification. Biotechniques. 2003; 35(2):254-6. DOI: 10.2144/03352bm01. View

Meathrel K, Adamek T, Batt J, Rotin D, Doering L . Protein tyrosine phosphatase sigma-deficient mice show aberrant cytoarchitecture and structural abnormalities in the central nervous system. J Neurosci Res. 2002; 70(1):24-35. DOI: 10.1002/jnr.10382. View

Seymour A, Andrews E, Tsai S, Markus T, Bollnow M, Brenneman M . Delayed treatment with monoclonal antibody IN-1 1 week after stroke results in recovery of function and corticorubral plasticity in adult rats. J Cereb Blood Flow Metab. 2005; 25(10):1366-75. DOI: 10.1038/sj.jcbfm.9600134. View

Massey J, Hubscher C, Wagoner M, Decker J, Amps J, Silver J . Chondroitinase ABC digestion of the perineuronal net promotes functional collateral sprouting in the cuneate nucleus after cervical spinal cord injury. J Neurosci. 2006; 26(16):4406-14. PMC: 6673998. DOI: 10.1523/JNEUROSCI.5467-05.2006. View

Nurcombe V, Ford M, Wildschut J, Bartlett P . Developmental regulation of neural response to FGF-1 and FGF-2 by heparan sulfate proteoglycan. Science. 1993; 260(5104):103-6. DOI: 10.1126/science.7682010. View

Rhodes K, Fawcett J . Chondroitin sulphate proteoglycans: preventing plasticity or protecting the CNS?. J Anat. 2003; 204(1):33-48. PMC: 1571240. DOI: 10.1111/j.1469-7580.2004.00261.x. View

10.

Sato Y, Nakanishi K, Hayakawa M, Kakizawa H, Saito A, Kuroda Y . Reduction of brain injury in neonatal hypoxic-ischemic rats by intracerebroventricular injection of neural stem/progenitor cells together with chondroitinase ABC. Reprod Sci. 2008; 15(6):613-20. DOI: 10.1177/1933719108317299. View

11.

Properzi F, Lin R, Kwok J, Naidu M, van Kuppevelt T, Ten Dam G . Heparan sulphate proteoglycans in glia and in the normal and injured CNS: expression of sulphotransferases and changes in sulphation. Eur J Neurosci. 2008; 27(3):593-604. DOI: 10.1111/j.1460-9568.2008.06042.x. View

12.

Nakamae T, Tanaka N, Nakanishi K, Kamei N, Sasaki H, Hamasaki T . The effects of combining chondroitinase ABC and NEP1-40 on the corticospinal axon growth in organotypic co-cultures. Neurosci Lett. 2010; 476(1):14-7. DOI: 10.1016/j.neulet.2010.03.049. View

13.

Jin K, Mao X, Greenberg D . Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc Natl Acad Sci U S A. 2000; 97(18):10242-7. PMC: 27841. DOI: 10.1073/pnas.97.18.10242. View

14.

Schallert T, Fleming S, Leasure J, Tillerson J, Bland S . CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury. Neuropharmacology. 2000; 39(5):777-87. DOI: 10.1016/s0028-3908(00)00005-8. View

15.

Fawcett J, Asher R . The glial scar and central nervous system repair. Brain Res Bull. 1999; 49(6):377-91. DOI: 10.1016/s0361-9230(99)00072-6. View

16.

Kirkham D, Pacey L, Axford M, Siu R, Rotin D, Doering L . Neural stem cells from protein tyrosine phosphatase sigma knockout mice generate an altered neuronal phenotype in culture. BMC Neurosci. 2006; 7:50. PMC: 1570144. DOI: 10.1186/1471-2202-7-50. View

17.

Nawashiro H, Tasaki K, Ruetzler C, Hallenbeck J . TNF-alpha pretreatment induces protective effects against focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 1997; 17(5):483-90. DOI: 10.1097/00004647-199705000-00001. View

18.

Xu J, Sun D, Liu X, Liu H, Hua X, Chen X . [Effect of chondroitinase ABC on growth associate protein 43 and glial fibrillary acidic protein after spinal cord injury in rats]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010; 24(10):1212-6. View

19.

Jin K, Mao X, Batteur S, McEachron E, Leahy A, Greenberg D . Caspase-3 and the regulation of hypoxic neuronal death by vascular endothelial growth factor. Neuroscience. 2001; 108(2):351-8. DOI: 10.1016/s0306-4522(01)00154-3. View

20.

Garcia-Alias G, Barkhuysen S, Buckle M, Fawcett J . Chondroitinase ABC treatment opens a window of opportunity for task-specific rehabilitation. Nat Neurosci. 2009; 12(9):1145-51. DOI: 10.1038/nn.2377. View