Outer radial glia promotes white matter regeneration after neonatal brain injury
Hideo Jinnou1, Lauren M Rosko2, Satoshi Yamashita2
1Center for Neuroscience Research, Children's National Research Institute, Children's National Hospital, Washington, DC 20010, USA; Department of Pediatrics and Neonatology, Nagoya City University, Graduate School of Medical Sciences, Nagoya 467-8601, Japan.
Abstract:
The developing gyrencephalic brain contains a large population of neural stem cells in the ventricular zone and outer subventricular zone (OSVZ), the latter populated by outer radial glia (oRG). The role of oRG during postnatal development is not well understood. We show that oRG cells increase proliferative capacity and contribute to oligodendrocyte precursor cell (OPC) production following brain injury in human infants and neonatal piglets, whose brains resemble the human brain in structure and development. RNA sequencing revealed oRG-specific transcriptional responses to injury in piglets and showed that the activating transcription factor 5 (ATF5) pathway positively regulates oRG proliferation. Intranasal activation of ATF5 using salubrinal enhanced OSVZ-derived oligodendrogenesis in the injured periventricular white matter and improved functional recovery. These results reveal a key role for postnatal oRG in brain injury recovery and identify ATF5 as a potential therapeutic target for treating white matter injury in infants.
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