title: Neuropilin 2 deficiency does not affect cortical neuronal viability in response to oxygen-glucose-deprivation and transient middle cerebral artery occlusion.
abstract: Neuropilin 2 (NRP2) is a type I transmembrane protein that binds to distinct members of the class III secreted Semaphorin subfamily. NRP2 plays important roles in repulsive axon guidance, angiogenesis and vasculogenesis through partnering with co-receptors such as vascular endothelial growth factor receptors (VEGFRs) during development. Emerging evidence also suggests that NRP2 contributes to injury response and environment changes in adult brains. In this study, we examined the contribution of NRP2 gene to cerebral ischemia-induced brain injury using NRP2 deficient mouse. To our surprise, the lack of NRP2 expression does not affect the outcome of brain injury induced by transient occlusion of the middle cerebral artery (MCAO) in mouse. The cerebral vasculature in terms of the middle cerebral artery anatomy and microvessel density in the cerebral cortex of NRP2 deficient homozygous (NRP2(-/-)) mice are normal and almost identical to those of the heterozygous (NRP2(+/-)) and wild type (NRP2(+/+)) littermates. MCAO (1h) and 24h reperfusion caused a brain infarction of 23% (compared to the contralateral side) in NRP2(-/-) mice, which is not different from those in NRP2(+/- and +/+) mice at 22 and 21%, respectively (n=19, p>0.05). Correspondingly, NRP2(-/-) mouse also showed a similar level of deterioration of neurological functions after stroke compared with their NRP2(+/- and +/+) littermates. Oxygen-glucose-deprivation (OGD) caused a significant neuronal death in NRP2(-/-) cortical neurons, at the level similar to that in NRP(+/+) cortical neurons (72% death in NRP(-/-) neurons vs. 75% death in NRP2(+/+) neurons; n=4; p>0.05). Together, these loss-of-function studies demonstrated that despite of its critical role in neuronal guidance and vascular formation during development, NRP2 expression dose not affect adult brain response to cerebral ischemia.
authors.affiliation: Experimental NeuroTherapeutics Laboratory, NRC Institute for Biological Sciences, National Research Council Canada, 1200 Montreal Road, Bldg M-54, Ottawa, ON, Canada K1A 0R6. Sheng.hou@nrc-cnrc.gc.ca
authors.forename: Sheng T
authors.initials: ST
authors.lastname: Hou
authors.forename: Susan X
authors.initials: SX
authors.lastname: Jiang
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Slinn
authors.forename: Michael
authors.initials: M
authors.lastname: O'Hare
authors.forename: Laurie
authors.initials: L
authors.lastname: Karchewski
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D005947:Glucose / Q000172:deficiency*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D039943:Neuropilin-2 / Q000096:biosynthesis / Q000235:genetics*; D010100:Oxygen / Q000502:physiology*
chemical_list: D039943:Neuropilin-2; D005947:Glucose; D010100:Oxygen