During development, neuropilin-1 is a receptor for semaphorin 3a-mediated a
xonal 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 immunohistoc
hemistry. Neuropilin-1 mRNA was significantly up-regulated as early as 2 ho
urs 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 i
n 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 expres
sion persisted on these vessels for at least 28 days after ischemia. In the
se areas. neovascularization was detected using three-dimensional reconstru
cted images obtained from laser scanning confocal microscopy. Activated ast
rocytes also exhibited neuropilin-1 immunoreactivity during 7 to 28 days of
ischemia. Double immunofluorescent staining showed colocalization of neuro
pilin-1 and VEGF to cerebral blood vessels and activated astrocytes. These
data suggest that in addition to its role in axonal growth, up-regulation o
f neuropilin-1, in concert with VEGF and its receptors, may contribute to n
eovascular formation in the adult ischemic brain.