Transient neurogenesis in ischemic cortex from Sox2⁺ astrocytes

Area of Science:

• Neuroscience
• Stem Cell Biology
• Cerebrovascular Disease

Background:

• The adult cerebral cortex was traditionally considered non-neurogenic.
• The capacity for neurogenesis in the adult cortex following injury remains a subject of debate.

Purpose of the Study:

• To investigate whether focal ischemia can induce neurogenesis in the adult cerebral cortex.
• To identify the cell types responsible for neurogenesis after ischemic injury.

Main Methods:

• Utilized 5'-bromo-2'-deoxyuridine (BrdU) labeling to track newly generated cells.
• Employed Nestin-Cre^ER, PDGFRα-, GFAP-, and Sox2-Cre^ER mice for cell ablation and fate mapping.
• Used a mini-photothrombotic ischemia model and retroviral labeling in mice and Macaca mulatta.

Main Results:

• Focal ischemia induced a transient wave of doublecortin-positive neuroblasts in the mouse cerebral cortex, which exhibited rapid cell death.
• A small contribution of neuroblasts originated from subventricular zone neural stem cells.
• Sox2-positive astrocytes were identified as the major source of neuroblasts in the ischemic adult cortex, with similar findings in non-human primates.
• Observed maturation of locally generated new neurons following ischemia.

Conclusions:

• Focal ischemia stimulates a transient, localized neurogenic response in the adult cerebral cortex.
• Sox2-positive astrocytes are key players in adult cortical neurogenesis after ischemic injury.
• These findings suggest potential therapeutic strategies for neuronal regeneration by enhancing intrinsic neurogenic responses.