Make sure your doctor is not inadvertantly giving you Nogo-A. You do want angiogenesis to supply blood to those new neurogenesis neurons and help those stunned neurons in the penumbra.
Nogo-A is a negative regulator of CNS angiogenesis
Abstract
Nogo-A is an important axonal
growth inhibitor in the adult and developing CNS. In vitro, Nogo-A has
been shown to inhibit
migration and cell spreading of neuronal
and nonneuronal cell types. Here, we studied in vivo and in vitro
effects of Nogo-A
on vascular endothelial cells during
angiogenesis of the early postnatal brain and retina in which Nogo-A is
expressed by
many types of neurons. Genetic ablation or
virus-mediated knock down of Nogo-A or neutralization of Nogo-A with an
antibody
caused a marked increase in the blood
vessel density in vivo. In culture, Nogo-A inhibited spreading,
migration, and sprouting
of primary brain microvascular endothelial
cells (MVECs) in a dose-dependent manner and induced the retraction of
MVEC lamellipodia
and filopodia. Mechanistically, we show
that only the Nogo-A–specific Delta 20 domain exerts inhibitory effects
on MVECs,
but the Nogo-66 fragment, an inhibitory
domain common to Nogo-A, -B, and -C, does not. Furthermore, the action
of Nogo-A Delta
20 on MVECs required the intracellular
activation of the Ras homolog gene family, member A (Rho-A)-associated,
coiled-coil
containing protein kinase (ROCK)-Myosin II
pathway. The inhibitory effects of early postnatal brain membranes or
cultured
neurons on MVECs were relieved
significantly by anti–Nogo-A antibodies. These findings identify Nogo-A
as an important negative
regulator of developmental angiogenesis in
the CNS. They may have important implications in CNS pathologies
involving angiogenesis
such as stroke, brain tumors, and
retinopathies.
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