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Updated: Dec 6, 2025
A Neonatal Mouse Spinal Cord Compression Injury Model
Published on: March 27, 2016
Microglia-organized scar-free spinal cord repair in neonatal mice
Yi Li1,2, Xuelian He1,2, Riki Kawaguchi3,4
1F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
Abstract:
Spinal cord injury in mammals is thought to trigger scar formation with little regeneration of axons1-4. Here we show that a crush injury to the spinal cord in neonatal mice leads to scar-free healing that permits the growth of long projecting axons through the lesion. Depletion of microglia in neonatal mice disrupts this healing process and stalls the regrowth of axons, suggesting that microglia are critical for orchestrating the injury response. Using single-cell RNA sequencing and functional analyses, we find that neonatal microglia are transiently activated and have at least two key roles in scar-free healing. First, they transiently secrete fibronectin and its binding proteins to form bridges of extracellular matrix that ligate the severed ends of the spinal cord. Second, neonatal-but not adult-microglia express several extracellular and intracellular peptidase inhibitors, as well as other molecules that are involved in resolving inflammation. We transplanted either neonatal microglia or adult microglia treated with peptidase inhibitors into spinal cord lesions of adult mice, and found that both types of microglia significantly improved healing and axon regrowth. Together, our results reveal the cellular and molecular basis of the nearly complete recovery of neonatal mice after spinal cord injury, and suggest strategies that could be used to facilitate scar-free healing in the adult mammalian nervous system.
Insights
Neonatal mice exhibit scar-free spinal cord injury healing, allowing axon regrowth. Microglia orchestrate this process by forming extracellular matrix bridges and resolving inflammation, offering potential therapeutic strategies for adult spinal cord injury.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Immunology
Background:
- Spinal cord injury (SCI) in mammals typically results in scar formation, inhibiting axon regeneration.
- Neonatal mammals display a remarkable capacity for recovery after SCI, contrasting with adult outcomes.
Purpose of the Study:
- To investigate the mechanisms underlying scar-free healing and axon regeneration in neonatal mice following SCI.
- To identify the role of microglia in facilitating this regenerative response.
Main Methods:
- Crush injury model in neonatal mice.
- Microglia depletion experiments.
- Single-cell RNA sequencing.
- Extracellular matrix analysis.
- Microglia transplantation studies in adult mice.
Main Results:
- Neonatal mice with SCI demonstrated scar-free healing and significant axon regrowth.
- Microglia depletion in neonates impaired healing and blocked axon regrowth, highlighting their critical role.
- Neonatal microglia were found to secrete fibronectin for extracellular matrix bridging and express peptidase inhibitors for inflammation resolution.
- Transplantation of neonatal microglia or modified adult microglia improved healing and axon regrowth in adult SCI models.
Conclusions:
- Neonatal microglia are essential for orchestrating scar-free spinal cord healing and axon regeneration through extracellular matrix formation and inflammation resolution.
- These findings reveal the cellular and molecular basis for neonatal recovery from SCI.
- Strategies involving microglia modulation show promise for promoting scar-free healing and axon regeneration in adult mammalian nervous systems.
