Bioluminescence imaging visualizes osteopontin-induced neurogenesis and neuroblast migration in the mouse brain after stroke

Stem Cell Research & Therapy, 2018 · DOI: https://doi.org/10.1186/s13287-018-0927-9 · Published: July 2, 2018

Simple Explanation

Osteopontin (OPN) is a protein upregulated in the brain after a stroke. This study used bioluminescence imaging (BLI) in mice to visualize the effects of OPN on neuroblasts, which are cells that develop into neurons. The study found that OPN enhanced the migration of neuroblasts in both healthy brains and after a stroke. This suggests OPN could help the brain repair itself by promoting the movement of new neurons to damaged areas. OPN also increased the number of neural progenitors, which are cells that can differentiate into various types of brain cells. This indicates OPN's potential to stimulate the generation of new brain cells after an injury like a stroke.

Study Duration

28 days

Participants

46 DCX-luc transgenic mice

Evidence Level

Not specified

Key Findings

1
OPN enhances the directed migration of neuroblasts in the healthy brain, as visualized by BLI, with maximal BLI signal observed at a significantly greater distance to the midline than under control conditions.
2
OPN expands neuroblast numbers in the healthy brain, with a significantly increased total flux ratio in OPN-treated mice compared with controls, indicating an expansion of DCX+ neuroblasts in the ipsilateral hemisphere.
3
OPN induces neuroblast migration after focal cortical ischemia, with significantly enhanced neuroblast migration between days 7 and 21 following treatment, and increased distance covered by neuroblasts compared with control conditions.

Research Summary

This study investigates the effect of osteopontin (OPN) on neuroblasts in healthy mice and after focal cerebral ischemia, using bioluminescence imaging (BLI) to assess neuroblast migration and expansion. The results demonstrate that OPN supports directed migration and expansion of the stem cell niche in vivo, both in healthy brains and after stroke, suggesting its potential for targeted activation of neurogenesis in ischemic stroke. The study also found that OPN quantitatively promoted the endogenous, ischemia-induced neuroblast expansion, and additionally recruited progenitors from the contralateral hemisphere after ischemia.

Practical Implications

Therapeutic potential for stroke

OPN constitutes a promising substance for the targeted activation of neurogenesis in ischemic stroke, potentially improving functional recovery.

Drug development

The study supports development of OPN-based therapies or mimetics to enhance neuroblast migration and neurogenesis after brain injury.

Understanding stroke recovery

Further research can explore the mechanisms by which OPN interacts with microglia and other immune cells to modulate neuroinflammation post-stroke.

Study Limitations

1
Potential interference of blood-brain barrier disruption with BLI signal interpretation.
2
The study used a photothrombosis model, which induces less extensive ischemic lesions compared to other stroke models.
3
Limited mechanistic insights into the long-term effects of OPN on functional recovery were provided.

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