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Low oral dose of 4-methylumbelliferone reduces glial scar but is insufficient to induce functional recovery after spinal cord injury
K. Štepánková, M. Chudíčková, Z. Šimková, N. Martinez-Varea, Š. Kubinová, LM. Urdzíková, P. Jendelová, JCF. Kwok
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
Wellcome Trust - United Kingdom
WT104818MA
Wellcome Trust - United Kingdom
MC-PC-16050
Medical Research Council - United Kingdom
Free Medical Journals od 2011
Nature Open Access od 2011-12-01
PubMed Central od 2011
Europe PubMed Central od 2011
ProQuest Central od 2011-01-01
Open Access Digital Library od 2011-01-01
Open Access Digital Library od 2011-01-01
Health & Medicine (ProQuest) od 2011-01-01
ROAD: Directory of Open Access Scholarly Resources od 2011
Odkazy
PubMed
37932336
DOI
10.1038/s41598-023-46539-5
Knihovny.cz E-zdroje
- MeSH
- chondroitinsulfát proteoglykany MeSH
- glióza patologie MeSH
- hymekromon terapeutické užití MeSH
- krysa rodu rattus MeSH
- kyselina hyaluronová MeSH
- mícha patologie MeSH
- poranění míchy MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Spinal cord injury (SCI) induces the upregulation of chondroitin sulfate proteoglycans (CSPGs) at the glial scar and inhibits neuroregeneration. Under normal physiological condition, CSPGs interact with hyaluronan (HA) and other extracellular matrix on the neuronal surface forming a macromolecular structure called perineuronal nets (PNNs) which regulate neuroplasticity. 4-methylumbelliferone (4-MU) is a known inhibitor for HA synthesis but has not been tested in SCI. We first tested the effect of 4-MU in HA reduction in uninjured rats. After 8 weeks of 4-MU administration at a dose of 1.2 g/kg/day, we have not only observed a reduction of HA in the uninjured spinal cords but also a down-regulation of CS glycosaminoglycans (CS-GAGs). In order to assess the effect of 4-MU in chronic SCI, six weeks after Th8 spinal contusion injury, rats were fed with 4-MU or placebo for 8 weeks in combination with daily treadmill rehabilitation for 16 weeks to promote neuroplasticity. 4-MU treatment reduced the HA synthesis by astrocytes around the lesion site and increased sprouting of 5-hydroxytryptamine fibres into ventral horns. However, the current dose was not sufficient to suppress CS-GAG up-regulation induced by SCI. Further adjustment on the dosage will be required to benefit functional recovery after SCI.
Department of Neuroscience Charles University 2nd Faculty of Medicine 15006 Prague Czech Republic
Faculty of Biological Sciences University of Leeds Leeds LS2 9JT UK
Institute of Experimental Medicine Czech Academy of Sciences Vídeňská 1083 Prague Czech Republic
Institute of Physics Czech Academy of Sciences 182 21 Prague Czech Republic
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- $a Spinal cord injury (SCI) induces the upregulation of chondroitin sulfate proteoglycans (CSPGs) at the glial scar and inhibits neuroregeneration. Under normal physiological condition, CSPGs interact with hyaluronan (HA) and other extracellular matrix on the neuronal surface forming a macromolecular structure called perineuronal nets (PNNs) which regulate neuroplasticity. 4-methylumbelliferone (4-MU) is a known inhibitor for HA synthesis but has not been tested in SCI. We first tested the effect of 4-MU in HA reduction in uninjured rats. After 8 weeks of 4-MU administration at a dose of 1.2 g/kg/day, we have not only observed a reduction of HA in the uninjured spinal cords but also a down-regulation of CS glycosaminoglycans (CS-GAGs). In order to assess the effect of 4-MU in chronic SCI, six weeks after Th8 spinal contusion injury, rats were fed with 4-MU or placebo for 8 weeks in combination with daily treadmill rehabilitation for 16 weeks to promote neuroplasticity. 4-MU treatment reduced the HA synthesis by astrocytes around the lesion site and increased sprouting of 5-hydroxytryptamine fibres into ventral horns. However, the current dose was not sufficient to suppress CS-GAG up-regulation induced by SCI. Further adjustment on the dosage will be required to benefit functional recovery after SCI.
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