Subventricular Zone-Derived Neuroblasts Migrate and Differentiate into Mature Neurons in the Post-Stroke Adult Striatum

TLDR

The adult mammalian brain can regenerate neurons after injury, but the mechanisms of insult‑induced neurogenesis remain unclear, and SVZ GFAP‑expressing cells normally generate only olfactory bulb neurons. This study demonstrates that after stroke, SVZ GFAP‑expressing cells can produce new neurons outside the olfactory bulb. SVZ GFAP cells generate neuroblasts that migrate to the injured striatum, form chain‑like aggregates associated with astrocytes and vessels, and ultimately differentiate into mature, synapse‑forming neurons, underscoring the SVZ’s regenerative potential after stroke.

Abstract

Recent studies have revealed that the adult mammalian brain has the capacity to regenerate some neurons after various insults. However, the precise mechanism of insult-induced neurogenesis has not been demonstrated. In the normal brain, GFAP-expressing cells in the subventricular zone (SVZ) of the lateral ventricles include a neurogenic cell population that gives rise to olfactory bulb neurons only. Herein, we report evidence that, after a stroke, these cells are capable of producing new neurons outside the olfactory bulbs. SVZ GFAP-expressing cells labeled by a cell-type-specific viral infection method were found to generate neuroblasts that migrated toward the injured striatum after middle cerebral artery occlusion. These neuroblasts in the striatum formed elongated chain-like cell aggregates similar to those in the normal SVZ, and these chains were observed to be closely associated with thin astrocytic processes and blood vessels. Finally, long-term tracing of the green fluorescent-labeled cells with a Cre-<i>loxP</i> system revealed that the SVZ-derived neuroblasts differentiated into mature neurons in the striatum, in which they expressed neuronal-specific nuclear protein and formed synapses with neighboring striatal cells. These results highlight the role of the SVZ in neuronal regeneration after a stroke and its potential as an important therapeutic target for various neurological disorders.