Neuropilin 2 deficiency does not affect cortical neuronal viability in response to oxygen–glucose-deprivation and transient middle cerebral artery occlusion
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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.
Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.