Cellular prion protein is increased in the plasma and peri-infarcted brain tissue after acute stroke.
The physiologic properties of the normal cellular prion protein (PrP(C)) have not been established fully, although recent evidence showed its upregulation in cerebral ischaemia. Using patients, animal models, and in vitro studies we aimed to identify in detail the expression and localization of PrP(C) in ischemic stroke. Patients in acute phase of ischaemic stroke had increased plasma levels of circulating PrP(C) as compared to healthy age- and gender-matched controls (3.1 +/- 1.4 vs. 1.9 +/- 0.7 ng/ml, P = 0.002). Immunohistochemistry showed increased expression of PrP(C) in the soma of peri-infarcted neurones as well as in the endothelial cells (EC) of micro-vessels and inflammatory cells in peri-infarcted brain tissue from patients who survived for 2-34 days after an initial stroke. The same pattern was repeated 1-48 hr after MCAO. RT-PCR showed increased gene expression of PrP(C) by human foetal neurons (HFN) after 12 hr of oxygen glucose deprivation (OGD), which remained increased after 24 hr reperfusion. Western blotting confirmed that protein expression was similarly upregulated, and fluorescent labeling showed a notable increase in peri-nuclear and axonal PrP(C) staining intensity. Increased plasma PrP(C) seems to reflect endogenous expression in acute stroke-affected brain tissue. Increased cellular expression in peri-infarcted regions may influence hypoxia-induced cell damage, although the effects on EC survival and angiogenesis remain to be elucidated.
Mitsios
Nicholas
N
School of Biology, Chemistry and Health Science, John Dalton Building, Manchester Metropolitan University, Manchester, United Kingdom.
Saka
Mohamad
M
Krupinski
Jerzy
J
Pennucci
Roberta
R
Sanfeliu
Coral
C
Miguel Turu
Marta
M
Gaffney
John
J
Kumar
Pat
P
Kumar
Shant
S
Sullivan
Matthew
M
Slevin
Mark
M
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002544:Cerebral Infarction / Q000378:metabolism*; D017931:DNA Primers; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery; D018621:PrPC Proteins / Q000097:blood / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018621:PrPC Proteins