Assessment of NgR1 Function In Vivo After Spinal Cord Injury

Neurosurgery, 2014 · DOI: 10.1227/NEU.0000000000000337 · Published: July 1, 2014

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates the role of NgR1, a protein that inhibits nerve regeneration, in spinal cord injury (SCI) using mice with and without the NgR1 gene. Researchers aimed to understand why previous studies showed conflicting results regarding NgR1's impact on recovery after SCI. The study found that the severity of the spinal cord injury influenced the recovery of motor function in mice lacking NgR1. Mice with a severe injury showed more improvement when NgR1 was absent compared to those with a moderate injury. The research suggests that while removing NgR1 alone may not be enough to promote extensive nerve regeneration across the injury site, it can enhance the sprouting of nerve fibers to the opposite side of the spinal cord, potentially contributing to functional recovery.

Study Duration

5 Weeks

Participants

29 twelve-week old mice, wild-type (n = 9), heterozygous (NgR1 +/−; n = 11), homozygous (NgR1 −/−; n = 9)

Evidence Level

Not specified

Key Findings

1
The level of functional recovery is affected by the degree of injury suffered, with NgR1 ablation leading to significant recovery in locomotor function following severe SCI.
2
NgR1 ablation enhanced local collateral sprouting in the mutant mice, indicating that it restricts nerve fiber growth to the contralateral spinal cord.
3
MMP-9, which degrades CSPGs, was significantly upregulated in the homozygous mutant mice compared to the heterozygous or wild-type mice, suggesting MMP-9 activity may require NgR1.

Research Summary

This study investigates the role of NgR1 in limiting axon regeneration after spinal cord injury (SCI). Using mice with varying degrees of NgR1 deficiency and SCI severity, the research aimed to clarify conflicting results from previous studies. The findings indicate that the extent of functional recovery after SCI is significantly influenced by the severity of the injury and the presence of NgR1. Specifically, NgR1 ablation leads to enhanced locomotor recovery following severe SCI and promotes local collateral sprouting. The study also reveals that NgR1 ablation is correlated with changes in levels of reactive astrocytes, chondroitin sulfate proteoglycans (CSPGs), and MMP-9, suggesting NgR1 may have a role in glial scar formation and CSPG degradation.

Practical Implications

Therapeutic Target

NgR1 antagonism, especially in cases of severe SCI, may produce appreciable functional recovery, suggesting it as a therapeutic target.

Combination Therapy

NgR1 antagonism may necessitate combination with other therapeutic measures such as spatial or temporal regulation of glial scar formation or CSPG degradation to induce significant improvements following SCI.

Injury Model Context

The in vivo function of NgR1 needs to be studied under the appropriate context, as the degree of locomotor recovery in NgR1-deficient mice is influenced by the severity of the injury.

Study Limitations

1
The study acknowledges potential developmental compensatory changes in gene expression in the genetically altered animals.
2
The complexity and redundancy of the inhibitory signaling pathways in the CNS may mask some important functions of NgR1.
3
The mechanisms and significance of the correlated changes in MMP-9, GFAP-expressing reactive astrocytes, and CSPGs are yet to be fully investigated.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury