Microneurotrophin BNN27 Reduces Astrogliosis and Increases Density of Neurons and Implanted Neural Stem Cell-Derived Cells after Spinal Cord Injury

Biomedicines, 2023 · DOI: https://doi.org/10.3390/biomedicines11041170 · Published: April 13, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the effects of a microneurotrophin called BNN27 on spinal cord injury (SCI) in mice. Microneurotrophins are small molecules that mimic the effects of natural neurotrophins, which are important for nerve cell survival and function. The researchers tested whether BNN27, given alone or in combination with neural stem cell (NSC) transplants, could improve recovery after SCI. NSCs are cells that can develop into different types of nerve cells and may help to repair damaged spinal cords. The results showed that BNN27, especially when combined with NSC transplants, helped to reduce scarring and increase the number of nerve cells at the injury site. This suggests that BNN27 could be a useful addition to treatments for SCI.

Study Duration

12 weeks

Participants

C57/BL6 male mice approximately 4 weeks old

Evidence Level

Not specified

Key Findings

1
Systemic administration of BNN27 signiﬁcantly reduced astrogliosis in mice SCI lesion sites at 12 weeks post injury.
2
Systemic administration of BNN27 increased neuron density in mice SCI lesion sites at 12 weeks post injury.
3
BNN27 administration increased the density of survived implanted NSC-derived cells.

Research Summary

This study evaluated the effects of microneurotrophin BNN27, an NGF analog, in a mouse dorsal column crush spinal cord injury (SCI) model. BNN27 was delivered systemically either by itself or combined with neural stem cell (NSC)-seeded collagen-based scaffold grafts. Systemic administration of BNN27 signiﬁcantly reduced astrogliosis and increased neuron density in mice SCI lesion sites at 12 weeks post injury. Furthermore, when BNN27 administration was combined with NSC-seeded PCS grafts, BNN27 increased the density of survived implanted NSC-derived cells This study provides evidence that small-molecule mimetics of endogenous neurotrophins can contribute to effective combinatorial treatments for SCI, by simultaneously regulating key events of SCI and supporting grafted cell therapies in the lesion site.

Practical Implications

Therapeutic Potential for SCI

Microneurotrophins like BNN27 may offer a novel approach for treating spinal cord injuries by promoting nerve cell survival and reducing scar tissue formation.

Enhancement of Cell Therapies

Combining BNN27 with neural stem cell transplantation could improve the survival and integration of the transplanted cells, leading to better outcomes.

Development of Combinatorial Treatments

This study supports the idea of using multiple therapies together to address the complex nature of SCI, with BNN27 potentially playing a key role in such combinations.

Study Limitations

1
Study conducted only in mice, results may not translate directly to humans
2
Systemic BNN27 administration did not improve locomotion recovery
3
The mechanisms of BNN27's effects on NSC survival and differentiation require further investigation

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