Neurogenesis in Ischemic Stroke Recovery

Ischemic stroke triggers a cascade of cellular and molecular events that culminate in the activation of endogenous neural stem and progenitor cells within specialised niches of the adult brain. Two principal reservoirs—the subventricular zone lining the lateral ventricles and the subgranular zone of the dentate gyrus—respond to oxygen and nutrient deprivation by increasing proliferation, migrating towards the peri-infarct zone and differentiating into neurons, astrocytes and oligodendrocytes. This process is orchestrated by a dynamic interplay of growth factors, chemokines and extracellular matrix cues, with the local vasculature serving both as a scaffold for cell migration and as a source of trophic support. Neuroinflammatory signals modulate the balance between regeneration and scarring, while epigenetic and post-transcriptional mechanisms fine-tune cell fate decisions. Although the majority of newly generated neurons fail to integrate and survive long term, advances in understanding the cellular microenvironment and signalling pathways have revealed opportunities to enhance functional recovery. Therapeutic strategies now aim to augment endogenous repair by manipulating angiogenic factors, chemotactic gradients and immune modulators, or by delivering bioengineered vesicles and small-molecule epigenetic regulators to improve neuronal survival, connectivity and behavioural outcomes.

Research from Nature Portfolio

Recent studies have elucidated how subventricular zone-derived cells contribute directly to structural and functional repair. Following experimental cortical ischaemia, neural precursor cells proliferate and migrate along chemokine gradients and perivascular routes to the lesion border. These undifferentiated precursors secrete vascular endothelial growth factor (VEGF) to support angiogenesis and neuronal survival, while local CXCL12–CXCR4 signalling guides their ectopic migration. Genetic ablation of these progenitors or blockade of VEGF markedly impairs both vascular remodelling and behavioural recovery, whereas replenishment of VEGF is sufficient to restore reparative responses. This work highlights a coordinated mechanism in which the peri-infarct vasculature attracts stem-cell-derived precursors that in turn foster a regenerative niche.

Neurogenesis in Ischemic Stroke Recovery publication trend

The graph below shows the total number of articles in neurogenesis in ischemic stroke recovery across all publications each year (not limited to Nature Index journals).

Technical terms

Subventricular zone (SVZ): A specialised neurogenic region lining the lateral ventricles where adult neural stem cells reside.

Neural progenitor cell (NPC): A lineage-committed cell derived from stem cells that can differentiate into neurons and glia.

m6A methylation: A reversible chemical modification of RNA that regulates transcript stability, splicing and translation.

Exosome: A nanoscale extracellular vesicle that transports proteins, lipids and nucleic acids between cells.

Chemokine gradient: A spatial distribution of signalling molecules that directs cell migration.

References

1. Subventricular zone cytogenesis provides trophic support for neural repair in a mouse model of stroke. Nature Communications (2023).
2. Role of STAT3‐FOXO3 Signaling in the Modulation of Neuroplasticity by PD‐L1‐HGF‐Decorated Mesenchymal Stem Cell‐Derived Exosomes in a Murine Stroke Model. Advanced Science (2024).
3. The m6A methylation and expression profiles of mouse neural stem cells after hypoxia/reoxygenation. Stem Cell Research & Therapy (2024).
4. Neurogenesis After Stroke: A Therapeutic Perspective. Translational Stroke Research (2020).
5. Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain. Frontiers in Cellular Neuroscience (2013).