A putative role for platelet-derived growth factor in angiogenesis and neuroprotection after ischemic stroke in humans

• Published in: Stroke (1970) Vol. 28; no. 3; pp. 564 - 573
• Main Authors: KRUPINSKI, J, ISSA, R, BUJNY, T, SLEVIN, M, KUMAR, P, KUMAR, S, KALUZA, J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-03-1997; American Heart Association, Inc
• Subjects: Aged; Aged, 80 and over; Antibody Specificity; Biological and medical sciences; Blotting, Western; Brain - blood supply; Brain - cytology; Brain - physiopathology; Brain Chemistry - physiology; Brain Ischemia - pathology; Brain Ischemia - physiopathology; Cell Communication - physiology; Cerebral Infarction - pathology; Cerebral Infarction - physiopathology; Cerebrovascular Disorders - pathology; Cerebrovascular Disorders - physiopathology; Female; Humans; Immunohistochemistry; In Situ Hybridization; Male; Medical sciences; Middle Aged; Neovascularization, Physiologic - physiology; Neuroglia - chemistry; Neuroglia - cytology; Neurology; Neurons - chemistry; Neurons - cytology; Platelet-Derived Growth Factor - analysis; Platelet-Derived Growth Factor - genetics; Platelet-Derived Growth Factor - immunology; Receptors, Platelet-Derived Growth Factor - analysis; Receptors, Platelet-Derived Growth Factor - genetics; RNA, Messenger - analysis; Vascular diseases and vascular malformations of the nervous system; Human; Nervous system diseases; Stroke; Pathophysiology; Cardiovascular disease; Neuroprotective agent; Cerebral disorder; Vascular disease; Angiogenesis; Ischemia; Central nervous system disease; Cerebrovascular disease; Platelet derived growth factor
• ISSN: 0039-2499; 1524-4628
• DOI: 10.1161/01.str.28.3.564

Growth factors control two important processes in infarcted tissue, ie, angiogenesis and gliosis. We recently reported that transforming growth factor-beta1 (TGF-beta1) 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.
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 alpha, and PDGF-R beta.
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 alpha and PDGF-R beta mainly on neurons, and PDGF-R beta 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.
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.