Changes in hyaluronan production and metabolism following ischaemic stroke in man.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72535
Title:
Changes in hyaluronan production and metabolism following ischaemic stroke in man.
Authors:
Al'Qteishat, Ahmed; Gaffney, John; Krupinski, Jerzy; Rubio, Francisco; West, David C; Kumar, Shant; Kumar, Patricia; Mitsios, Nick; Slevin, Mark
Abstract:
The extent of recovery from stroke is dependent on the survival of neurons, particularly in peri-infarcted regions. Angiogenesis is critical for the development of new microvessels and leads to re-formation of collateral circulation, reperfusion and better recovery. Hyaluronan (HA) is an important component of the brain extracellular matrix and a regulator of cellular differentiation, migration, proliferation and angiogenesis. We have found that the production of total HA and low molecular mass 3-10 disaccharides of HA (o-HA) was increased in post-mortem tissue and in the serum of patients 1, 3, 7 and 14 days (peaking at 7 days) after ischaemic stroke. Hyaluronidase activity was also increased in serum samples (peaking after 3 days), which might explain the subsequent increase in o-HA. Affinity-histochemical staining was performed using a HA-specific biotinylated binding protein, and it showed enhanced deposition of HA in blood vessels and intracellularly as well as in the nuclei of peri-infarcted neurons. Western blotting and immunohistochemistry demonstrated upregulation of HA synthases (HAS1 and 2) and hyaluronidases (HYAL1 and 2) in inflammatory cells from both stroke and peri-infarcted regions of the brain. HYAL1 was upregulated in microvesssels and intracellularly in neurons, whilst HAS2 became translocated into the nuclei of neurons in peri-infarcted areas. Receptor for HA-mediated motility was observed intracellularly and in the nuclei of neurons, in the tunica media of larger blood vessels and in the endothelial cells of microvessels in stroke-affected tissue, whilst expression of other receptors for HA, CD44 and tumour necrosis factor-stimulated gene 6 (TSG-6) were mainly increased in infiltrating mononuclear cells from inflammatory regions. The data presented here demonstrate that HA breakdown is a feature of the acute stage of stroke injury. Increased o-HA production soon after stroke may be detrimental through enhancement of the inflammatory response, whilst activation of HA and/or o-HA-induced cellular signalling pathways in neurons and microvessels may impact on the remodelling process by stimulating angiogenesis and revascularization, as well as the survival of susceptible neurons.
Affiliation:
Department of Biology, Chemistry and Health Science, Manchester Metropolitan University, Liverpool, UK.
Citation:
Changes in hyaluronan production and metabolism following ischaemic stroke in man. 2006, 129 (Pt 8):2158-76 Brain
Journal:
Brain
Issue Date:
Aug-2006
URI:
http://hdl.handle.net/10541/72535
DOI:
10.1093/brain/awl139
PubMed ID:
16731541
Type:
Article
Language:
en
ISSN:
1460-2156
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorAl'Qteishat, Ahmed-
dc.contributor.authorGaffney, John-
dc.contributor.authorKrupinski, Jerzy-
dc.contributor.authorRubio, Francisco-
dc.contributor.authorWest, David C-
dc.contributor.authorKumar, Shant-
dc.contributor.authorKumar, Patricia-
dc.contributor.authorMitsios, Nick-
dc.contributor.authorSlevin, Mark-
dc.date.accessioned2009-07-06T10:24:08Z-
dc.date.available2009-07-06T10:24:08Z-
dc.date.issued2006-08-
dc.identifier.citationChanges in hyaluronan production and metabolism following ischaemic stroke in man. 2006, 129 (Pt 8):2158-76 Brainen
dc.identifier.issn1460-2156-
dc.identifier.pmid16731541-
dc.identifier.doi10.1093/brain/awl139-
dc.identifier.urihttp://hdl.handle.net/10541/72535-
dc.description.abstractThe extent of recovery from stroke is dependent on the survival of neurons, particularly in peri-infarcted regions. Angiogenesis is critical for the development of new microvessels and leads to re-formation of collateral circulation, reperfusion and better recovery. Hyaluronan (HA) is an important component of the brain extracellular matrix and a regulator of cellular differentiation, migration, proliferation and angiogenesis. We have found that the production of total HA and low molecular mass 3-10 disaccharides of HA (o-HA) was increased in post-mortem tissue and in the serum of patients 1, 3, 7 and 14 days (peaking at 7 days) after ischaemic stroke. Hyaluronidase activity was also increased in serum samples (peaking after 3 days), which might explain the subsequent increase in o-HA. Affinity-histochemical staining was performed using a HA-specific biotinylated binding protein, and it showed enhanced deposition of HA in blood vessels and intracellularly as well as in the nuclei of peri-infarcted neurons. Western blotting and immunohistochemistry demonstrated upregulation of HA synthases (HAS1 and 2) and hyaluronidases (HYAL1 and 2) in inflammatory cells from both stroke and peri-infarcted regions of the brain. HYAL1 was upregulated in microvesssels and intracellularly in neurons, whilst HAS2 became translocated into the nuclei of neurons in peri-infarcted areas. Receptor for HA-mediated motility was observed intracellularly and in the nuclei of neurons, in the tunica media of larger blood vessels and in the endothelial cells of microvessels in stroke-affected tissue, whilst expression of other receptors for HA, CD44 and tumour necrosis factor-stimulated gene 6 (TSG-6) were mainly increased in infiltrating mononuclear cells from inflammatory regions. The data presented here demonstrate that HA breakdown is a feature of the acute stage of stroke injury. Increased o-HA production soon after stroke may be detrimental through enhancement of the inflammatory response, whilst activation of HA and/or o-HA-induced cellular signalling pathways in neurons and microvessels may impact on the remodelling process by stimulating angiogenesis and revascularization, as well as the survival of susceptible neurons.en
dc.language.isoenen
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntigens, CD44-
dc.subject.meshBlood Vessels-
dc.subject.meshBrain-
dc.subject.meshCell Adhesion Molecules-
dc.subject.meshCerebral Infarction-
dc.subject.meshExtracellular Matrix Proteins-
dc.subject.meshFemale-
dc.subject.meshGlucuronosyltransferase-
dc.subject.meshHumans-
dc.subject.meshHyaluronic Acid-
dc.subject.meshHyaluronoglucosaminidase-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeurons-
dc.subject.meshUp-Regulation-
dc.titleChanges in hyaluronan production and metabolism following ischaemic stroke in man.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biology, Chemistry and Health Science, Manchester Metropolitan University, Liverpool, UK.en
dc.identifier.journalBrainen

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