Brain injuries such as
trauma and
stroke lead to
glial scar formation by reactive
astrocytes which produce and secret axonal outgrowth inhibitors.
Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of
extracellular matrix molecules produced at the
glial scar and cause
growth cone collapse. The CSPG
glycosaminoglycan side chains composed of
chondroitin sulfate (CS) are responsible for its inhibitory activity on
neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs
neural stem cell migration inhibiting their penetration into an
injury site. We show that DCX+ neuroblasts do not penetrate a CSPG-rich injured area probably due to
Nogo receptor activation and RhoA/ROCK signaling pathway as we demonstrate
in vitro with
neural stem cells cultured as neurospheres and pull-down for RhoA. Furthermore, CS-impaired
cell migration in vitro induced the formation of large mature adhesions and altered
cell protrusion dynamics. ROCK inhibition restored migration
in vitro as well as decreased adhesion size.