Cell Type-Specific Expression of Neuropilins in an MCA-Occlusion Model in Mice Suggests a Potential Role in Post-Ischemic Brain Remodeling

• Published in: Journal of neuropathology and experimental neurology 2002-04, Vol.61 (4), p.339-350
• Main Authors: BECK, HEIKE, ACKER, TILL, PÜSCHEL, ANDREAS W, FUJISAWA, HAJIME, CARMELIET, PETER, PLATE, KARL H
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - metabolism; Brain - metabolism; Brain - pathology; Brain Ischemia - metabolism; Brain Ischemia - pathology; Carrier Proteins - metabolism; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cerebral Infarction - metabolism; Cerebral Infarction - pathology; Disease Models, Animal; Endothelial Growth Factors - genetics; Endothelial Growth Factors - metabolism; Female; Immunohistochemistry; In Situ Hybridization; Infarction, Middle Cerebral Artery; Lymphokines - genetics; Lymphokines - metabolism; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Models, Neurological; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Neuropilin-1; Placenta Growth Factor; Pregnancy Proteins - genetics; Pregnancy Proteins - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Receptor Protein-Tyrosine Kinases - genetics; Receptor Protein-Tyrosine Kinases - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Growth Factor - genetics; Receptors, Growth Factor - metabolism; Receptors, Vascular Endothelial Growth Factor; Semaphorin-3A; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factors
• ISSN: 0022-3069; 1554-6578
• DOI: 10.1093/jnen/61.4.339

Neuropilin-1 and -2 (NP-1/NP-2) are transmembrane receptors that play a role in axonal guidance by binding of class III semaphorins, and in angiogenesis by binding of the vascular endothelial growth factor isoform VEGF165 and placenta growth factor (PLGF). We investigated the expression pattern of NP-1/NP-2, their co-receptors, vascular endothelial growth factor receptor-1 and -2 (VEGFR-1, VEGFR-2), and their ligands, class III semaphorins, VEGF and PLGF, following experimental cerebral ischemia in mice. By means of in situ hybridization and immunohistochemistry we observed loss of expression of class III semaphorins in neurons in the infarct/peri-infarct area. In contrast, we observed high expression of NP-1 in vessels, neurons, and astrocytes surrounding the infarct. VEGF and PLGF were upregulated in different cell types following stroke. Our results suggest a shift in the balance between semaphorins and VEGF/PLGF, which compete for NP-binding. Possibly, the loss of semaphorins facilitates binding of the competing ligands (VEGF/PLGF), thus inducing angiogenesis. In addition, the observed expression patterns further suggest a neurotrophic/neuroprotective role of VEGF/PLGF.