A PUTATIVE ROLE FOR PLATELET-DERIVED GROWTH-FACTOR IN ANGIOGENESIS AND NEUROPROTECTION AFTER ISCHEMIC STROKE IN HUMANS

Background and Purpose Growth factors control two important processes in infarcted tissue, ie, angiogenesis and gliosis. We recently reporte d that transforming growth factor-beta 1 (TGF-beta 1) might be involve d in angiogenesis after ischemic stroke in humans; here we present dat a of an extensive study on platelet-derived growth factor (PDGF) and i ts receptors. Methods We studied brain samples from patients who suffe red from ischemic stroke for the expression of mRNA encoding PDGF-A, P DGF-B, and PDGF receptors (PDGF-R). Proteins were examined by Western blotting and immunohistochemistry using the antibodies to PDGF-AB, PDG F-BB, PDGF-R alpha, and PDGF-R beta. 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 ne urons in infarct and penumbra. The least expression was seen in the co ntralateral hemisphere (P<.001). In contrast, both PDGF-AB and PDGF-BB immunoreactive products were present in most cell types: PDGF-R alpha and PDGF-RP mainly on neurons, and PDGF-R beta on some endothelial ce lls, with less staining of all the isoforms in the contralateral hemis phere. On Western blots, PDGF-AB and -BB were expressed more within wh ite matter than gray matter of infarct/penumbra, whereas both isoforms of receptor were expressed mainly in gray matter compared with contra lateral hemisphere. There was no or very weak expression of the recept or in white matter. Conclusions PDGF proteins are highly expressed in white matter, suggesting that PDGF may exert its function in white mat ter participating either in regeneration of damaged axons or in glial scar formation. PDGF-BB and its receptor expressed on microvessel endo thelial cells might be involved in angiogenesis after stroke. Thus, PD GF is likely to be angiogenic and neuroprotective in stroke.