Or is it all just coasting on school knowledge?
And its only 7 years old.
http://brain.oxfordjournals.org/content/129/8/2158.short
- Ahmed Al'Qteishat1,
- John Gaffney1,
- Jerzy Krupinski4,5,
- Francisco Rubio4,5,
- David West3,
- Shant Kumar2,
- Patricia Kumar1,
- Nicholas Mitsios1 and
- Mark Slevin1
+ Author Affiliations
- Correspondence to: Mark Slevin, Department of Biology, Chemistry and Health Science, Manchester Metropolitan University, Manchester M1 5GD, UK E-mail: m.a.slevin@mmu.ac.uk
- Received January 20, 2006.
- Revision received April 24, 2006.
- Accepted April 26, 2006.
Summary
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.
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