(Stroke. 1997;28:564-573.)
© 1997 American Heart Association, Inc.
Articles |
A Putative Role for Platelet-Derived Growth Factor in Angiogenesis and Neuroprotection After Ischemic Stroke in Humans
From the Department of Biological Sciences, Manchester Metropolitan University (J. Krupinski, R.I., M.S., P.K.); the Department of Clinical Neurosciences, Institute of Psychiatry and King's College School of Medicine and Dentistry, London (J. Krupinski); the Christie Hospital, Manchester (S.K.), UK; and the Department of Neuropathology, Jagiellonian University, Kracow, Poland (J. Krupinski, T.B., J. Kaluza).
Correspondence to Jerzy Krupinski, MD, PhD, Department of Clinical Neurosciences, Institute of Psychiatry and King's College School of Medicine and Dentistry, London SE5 8AF, UK.
Background and Purpose Growth factors control two important processes in infarcted tissue, ie, angiogenesis and gliosis. We recently reported that transforming growth factor-ß1 (TGF-ß1) might be involved in angiogenesis after ischemic stroke in humans; here we present data of an extensive study on platelet-derived growth factor (PDGF) and its receptors.
Methods We studied brain samples from patients who suffered
from ischemic stroke for the expression of mRNA encoding PDGF-A,
PDGF-B, and PDGF receptors (PDGF-R). Proteins were examined by Western
blotting and immunohistochemistry using the antibodies to PDGF-AB,
PDGF-BB, PDGF-R
, and PDGF-Rß.
Results At the mRNA level, PDGF-A and PDGF-B were expressed
mainly in neurons in penumbra. PDGF-R mRNA was strongly expressed in
some astrocytes but mainly in type III/IV neurons in infarct and
penumbra. The least expression was seen in the contralateral hemisphere
(P<.001). In contrast, both PDGF-AB and PDGF-BB
immunoreactive products were present in most cell types: PDGF-R and
PDGF-Rß mainly on neurons, and PDGF-Rß on some endothelial cells,
with less staining of all the isoforms in the contralateral hemisphere.
On Western blots, PDGF-AB and -BB were expressed more within white
matter than gray matter of infarct/penumbra, whereas both isoforms of
receptor were expressed mainly in gray matter compared with
contralateral hemisphere. There was no or very weak expression of the
receptor in white matter.
Conclusions PDGF proteins are highly expressed in white matter, suggesting that PDGF may exert its function in white matter participating either in regeneration of damaged axons or in glial scar formation. PDGF-BB and its receptor expressed on microvessel endothelial cells might be involved in angiogenesis after stroke. Thus, PDGF is likely to be angiogenic and neuroprotective in stroke.
Key Words: angiogenesis • cerebral ischemia • growth factors • neuroprotection
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