【Research News】Radial glial fibers promote neuronal migration and functional recovery after neonatal brain injury
Neonatal brain injury is a primary cause of childhood mortality and long-lasting disability. Much recent research has focused on the remarkable neurogenic capacity of neural stem cells (NSCs) in the ventricular-subventricular zone (V-SVZ) in the neonatal human brain, in which NSCs generate new neurons that migrate for a long distance. These observations raise the possibility that the neonatal V-SVZ is a source for endogenous neural regeneration in the neonatal brain. However, how V-SVZ-derived new neurons reach a lesion and contribute to neuronal regeneration and neurological recovery in the injured neonatal brain has not been fully studied.
Radial glia are polarized embryonic NSCs, which guide newly generated neurons by providing their fibers as a migratory scaffold. Soon after birth, the radial glia rapidly disappear. However, it remains unknown whether radial glia are retained after a neonatal brain injury.
In this study, researchers at Nagoya City University found that radial glial fibers are maintained for an extended period in the injured neonatal mouse brain and provide a scaffold on which V-SVZ-derived new neurons migrate toward the injured cerebral cortex. Furthermore, they found that in this process, N-cadherin-mediated cell-cell contact promotes RhoA activation in the new neurons and maintains their directional saltatory movement along radial glial fibers. In addition, they showed that inserting radial glial fiber-mimetic scaffold into the brain promoted new-neuron migration toward the lesion and facilitated neuronal regeneration and neurological recovery.
This study revealed the functional significance of neonatal radial glia after brain injury. Moreover, they propose a novel therapeutic strategy for repairing the injured neonatal brain and improving impaired gait behaviors using endogenous neurogenesis in the V-SVZ.
Newborn neurons (green) generated by neural stem cells (blue) migrate along radial glial fibers (red) toward injured cortex and differentiate into mature neurons.
Published Online Date :22 December, 2017
Journal:Cell Stem Cell
|Title||Radial glial fibers promote neuronal migration and functional recovery after neonatal brain injury|
|Author||Hideo Jinnou, Masato Sawada, Koya Kawase, Naoko Kaneko, Vicente Herranz-Pérez, Takuya Miyamoto, Takumi Kawaue, Takaki Miyata, Yasuhiko Tabata, Toshihiro Akaike, José Manuel García-Verdugo, Itsuki Ajioka, Shinji Saitoh, Kazunobu Sawamoto|