Reduction of Brain Injury in Neonatal Hypoxic—Ischemic Rats by Intracerebroventricular Injection of Neural Stem/Progenitor Cells Together With Chondroitinase ABC

Sato, Yoshiaki; Nakanishi, Kazuyoshi; Hayakawa, Masahiro; Kakizawa, Hiroko; Saito, Akiko; Kuroda, Yoshiyuki; Ida, Michiru; Tokita, Yoshihito; Aono, Sachiko; Matsui, Fumiko; Kojima, Seiji; Oohira, Atsuhiko

doi:10.1177/1933719108317299

Cited by 48 publications

(39 citation statements)

References 46 publications

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“…Other studies have shown effects of ChABC on axonal conduction, synapse formation, cell adhesion, growth factor diffusion, neuronal nets, and inflammation (5,11,28,29). In contrast, one prior study found no effect of ChABC, given as a single intracerebroventricular injection 24 h after neonatal hypoxic-ischemic brain injury in rats, on the wet weight of surviving brain tissue (30).…”

Section: Discussionmentioning

confidence: 92%

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

Hill

Jin

Mao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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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.astrocyte | astrogliosis | glia P atients who survive an acute stroke are typically left with fixed anatomical deficits and associated functional impairment in the chronic phase of injury, for which few therapeutic options exist. One reason for limited recovery from stroke may be the development of a glial scar at the border between normal and ischemic tissue (1, 2). The glial scar, which contains reactive astrocytes and associated extracellular matrix (ECM) proteins such as chondroitin sulfate proteoglycans (CSPGs) (3, 4), appears to serve a beneficial function in the acute phase of stroke, by confining the lesion and limiting toxic effects on adjacent tissue (5). However, it also inhibits axonal growth and, perhaps, other repair processes (1, 6, 7), thereby interfering with long-term anatomical and functional recovery. Conversely, some ECM proteins, such as the heparan sulfate proteoglycan (HSPG) glypican (8), can stimulate neurite growth after CNS injury (9). The role of these proteins in inhibition of recovery by the postischemic glial scar and the effect of their modification on functional and anatomical outcome from stroke are unknown.CSPGs, a major constituent of the glial scar (10), exist in several isoforms (11). Despite variations in their core proteins, CSPG isoforms share a conserved glycosaminoglycan side chain, which appears to inhibit axonal migration. CSPGs such as neurocan are powerful inhibitors of axonal growth cones and neurite extension in vitro (11), but this effect can be overco...

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Section: Discussionmentioning

confidence: 92%

“…Whether the effects of ChABC or glypican and such antibodies are additive will be of interest to explore, as will the combined effects of ChABC or glypican and transplantation, which has proved more efficacious than either treatment alone in models of retinal degeneration (40), neonatal hypoxia-ischemia (30), and spinal cord injury (41).…”

Section: Discussionmentioning

confidence: 99%

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

Hill

Jin

Mao

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…As a result, an improved motor function is observed in the treated animals (Daadi et al, 2010). It was also reported that NSPC can decrease HI brain injury, when injected in combination with chondroitinase ABC, an enzyme that degrades glycosaminoglycans side chains of chondroitin sulphate proteoglicans (Sato et al, 2008).…”

Section: Neural Stem/progenitor Cell Transplantation In Hiementioning

confidence: 87%

Future Perspectives for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy

Pimentel‐Coelho¹,

Santiago²,

Mendez-Otero³

2012

Miscellanea on Encephalopathies - A Second Look

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“…Referência Yasuhara et al 57 Sato et al 28 de Paula et al 38 Yasuhara et al 40 PimentelCoelho et al 37 Jenny et al 31 van Velthoven et al 56 Lee et al 55 ↓ dano cerebral (CTN+ChABC < CTN = VEH); ↑ peso cerebral (CTN+ChABC > CTN = VEH) (7 dias pT) Nenhum efeito sobre a atrofia cerebral 3 semanas pT ↑ níveis cerebrais de GDNF, BDNF e NGF 3 dias pT (CTCUH < CTCUH+M); ↑ densidade dendrítica na região hipocampal de CA1 14 dias pT ↓ morte neuronal e expressão de caspase 3 no estriado isquêmico 2 dias pT; ↓ ativação microglial no córtex 7 dias pT Formação de agrupamentos celulares com superexpressão de FGF-2 em áreas perivasculares T-P12: ↓ lesão cerebral (18 dias pT); ↑ neuro-e oligodendrogênese, e ↓ proliferação microglial no hipocampo e córtex isquêmico (7 e 18 dias pT); ↑ proliferação de astrócitos no hipocampo, e ↓ no córtex isquêmico (7 dias pT). T-P19: ↓ lesão cerebral (18 dias pT) Nenhum efeito sobre a atrofia cerebral 6 semanas pT…”

Section: Tabela 1 -Revisão Das Publicações Sobre Terapia Celular Em Hunclassified

“…Um exemplo disso é a utilização de condroitinase ABC (ChABC) associada ao transplante intracerebroventricular de CTN em ratos neonatos submetidos à HI que resultou na redução acentuada do dano cerebral 28 . Devido à capacidade de promover plasticidade cerebral, os autores sugerem que a ChABC teria facilitado a adesão e migração de CTN para áreas isquêmicas.…”

Section: Migração Celularunclassified

Use of stem cells in perinatal asphyxia: from bench to bedside

Paula¹,

Greggio²,

Costa³

2010

J Pediatr (Rio J)

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Objectives: To present recent scientific evidence on the effects of stem cell transplantation in animal models of neonatal hypoxic-ischemic brain injury and address the translational relevance of cell therapy for clinical application in this context. Sources:The PubMed and Scopus databases were used to select articles. The selection criterion was the specificity of articles regarding the subject studied, preferably articles published from 2000 onward. We also reviewed classic articles from previous years that were applicable to this review. Summary of the findings:Stem cells from different exogenous sources may exhibit neuroprotective properties in experimental models of neonatal hypoxia-ischemia. In most animal experiments, the morphological and functional benefits observed were independent of neural differentiation, suggesting associated mechanisms of action, such as the release of trophic factors and inflammatory modulation. Conclusions:Based on the experimental studies analyzed, cell therapy may become a promising therapeutic approach in the treatment of children with hypoxic-ischemic encephalopathy. However, further studies are warranted to elucidate potential mechanisms of action of these cells and to define safe and effective clinical strategies.J Pediatr (Rio J). 2010;86(6):451-464: Hypoxic-ischemic encephalopathy, stem cells, asphyxia, cell therapy. ResumoObjetivos: Apresentar evidências científicas recentes sobre os efeitos do transplante com células-tronco em modelos animais de lesão cerebral hipóxico-isquêmica neonatal e abordar os aspectos translacionais relevantes à aplicação clínica da terapia celular nesse contexto. Fonte dos dados:Para a seleção dos artigos, utilizou-se a base de dados PubMed e Scopus. O critério de seleção de artigos foi a especificidade em relação ao tema estudado, preferencialmente a partir do ano de 2000. Também foram revisados artigos clássicos de anos anteriores que se aplicavam ao propósito desta revisão. Síntese dos dados:Células-tronco de diferentes fontes exógenas podem exibir propriedades neuroprotetoras em modelos experimentais de hipóxia-isquemia neonatal. Na maioria dos experimentos animais, os benefícios morfológicos e funcionais observados foram independentes da diferenciação neural, sugerindo mecanismos de ação associados, tais como a liberação de fatores tróficos e a modulação inflamatória. Conclusões:Baseado nos estudos experimentais analisados, a terapia celular pode tornar-se uma promissora abordagem terapêutica no tratamento de crianças com encefalopatia hipóxico-isquêmica. No entanto, estudos adicionais necessitam ser realizados a fim de elucidar os possíveis mecanismos de ação dessas células e definir estratégias clínicas seguras e efetivas.J Pediatr (Rio J). 2010;86(6):451-464: Encefalopatia hipóxico-isquêmica, células-tronco, asfixia, terapia celular.

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Reduction of Brain Injury in Neonatal Hypoxic—Ischemic Rats by Intracerebroventricular Injection of Neural Stem/Progenitor Cells Together With Chondroitinase ABC

Cited by 48 publications

References 46 publications

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

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

Future Perspectives for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy

Use of stem cells in perinatal asphyxia: from bench to bedside

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