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Updated: Jul 17, 2026
Modeling Stroke in Mice: Focal Cortical Lesions by Photothrombosis
Published on: May 6, 2021
Aberrant Hippocampal Neurogenesis Is a Conserved Response to Stroke in Mice: A Multicenter Multimodel Study
Francisco J De Castro-Millán1,2, Sandra Vázquez-Reyes1,2, Carolina Peña-Martínez1,2,3
1Cardiovascular Risk Factors and Brain Health Programme, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain (F.J.D.C.-M., S.V.-R., C.P.-M., A.R.-L., C.P.-P., C.N.-V., A.G.-C., M.I.C., M.A.M.).
Stroke increases newborn hippocampal neuron production, but many display abnormal features affecting integration. This study found aberrant neurogenesis is a consistent post-stroke outcome across different mouse models, highlighting the need to assess neuron quality, not just quantity.
Area of Science:
- Neuroscience
- Stroke Research
- Neurogenesis
Background:
- Adult hippocampal neurogenesis is altered following cerebral ischemia.
- Stroke increases newborn neuron production, but many exhibit aberrant morphology and positioning, potentially impairing functional integration and cognitive deficits.
- The conservation of post-stroke neurogenic alterations across different experimental models remains unclear due to clinical heterogeneity and limited translational success.
Purpose of the Study:
- To identify common and model-specific features of hippocampal neurogenesis across various focal ischemia models.
- To investigate whether post-stroke neurogenic alterations are conserved across different experimental paradigms.
Main Methods:
- A multicenter, multimodel analysis using permanent and transient middle cerebral artery occlusion paradigms in adult C57BL/6J mice.
- Analysis at 3 days, 7 days, and 2 months post-ischemia, sham, or naïve conditions.
- Quantification of hippocampal proliferation (Ki67) and neuroblasts (DCX), alongside high-resolution assessment of dendritic architecture and somatodendritic polarity of newborn neurons.
Main Results:
- Ischemia robustly increased bilateral hippocampal proliferation, peaking at 3 days and remaining elevated at 7 days, normalizing by 2 months.
- Neuroblast density increased at 7 days, particularly ipsilaterally, but normalized over time.
- Long-term analysis revealed consistent reductions in apical dendrite length and increased aberrant neuronal features (ectopic positioning, polarity defects, abnormal growth) across all models.
Conclusions:
- Aberrant hippocampal neurogenesis is a consistent hallmark of post-stroke pathology in mice, irrespective of ischemia type or surgical approach.
- These findings emphasize the importance of evaluating the structural quality, not solely the quantity, of newborn neurons in post-stroke plasticity.
- Considering neurogenesis quality is crucial for developing effective therapeutic strategies for stroke recovery.
