Up-regulation of neuropilin-1 in neovasculature after focal cerebral ischemia in the adult rat.
During development, neuropilin-1 is a receptor for semaphorin 3a-mediated axonal guidance and for vascular endothelial growth factor (VEGF) promotion of angiogenesis. The authors measured neuropilin-1 expression in the adult ischemic brain using Northern blot, in situ hybridization, and immunohistochemistry. Neuropilin-1 mRNA was significantly up-regulated as early as 2 hours and persisted at least 28 days after focal cerebral ischemia. Acute up-regulation of neuropilin-1 mRNA primarily localized to the ischemic neurons. A marked increase in both mRNA and protein of neuropilin-1 was detected in endothelial cells of cerebral blood vessels at the border and in the core of the ischemic lesion 7 days after ischemia, and neuropilin-1 gene expression persisted on these vessels for at least 28 days after ischemia. In these areas, neovascularization was detected using three-dimensional reconstructed images obtained from laser scanning confocal microscopy. Activated astrocytes also exhibited neuropilin-1 immunoreactivity during 7 to 28 days of ischemia. Double immunofluorescent staining showed colocalization of neuropilin-1 and VEGF to cerebral blood vessels and activated astrocytes. These data suggest that in addition to its role in axonal growth, up-regulation of neuropilin-1, in concert with VEGF and its receptors, may contribute to neovascular formation in the adult ischemic brain.
Zhang
Z G
ZG
Department of Neurology, Henry Ford Health Sciences Center, Detroit, USA.
Tsang
W
W
Zhang
L
L
Powers
C
C
Chopp
M
M
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015152:Blotting, Northern; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D018076:DNA, Complementary; D016228:Endothelial Growth Factors / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism; D017403:In Situ Hybridization; D008222:Lymphokines / Q000032:analysis; D008297:Male; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D039942:Neuropilin-1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D039942:Neuropilin-1