Axonal Regeneration after Sciatic Nerve Lesion Is Delayed but Complete in GFAP- and Vimentin-Deficient Mice

PLoS ONE, 2013 · DOI: 10.1371/journal.pone.0079395 · Published: November 1, 2013

Regenerative Medicine Neurology Genetics

Simple Explanation

This study investigates how nerve cells regrow after injury in mice that lack certain proteins (GFAP and vimentin) found in support cells of the nervous system. These proteins are usually upregulated in response to injury. The researchers found that in mice lacking these proteins, the regrowth of nerve fibers was slower, and the connections between nerves and muscles took longer to re-establish. However, the eventual outcome was complete recovery. The absence of GFAP and vimentin seems to affect the speed of recovery after nerve damage, but doesn't prevent the nerves from fully healing.

Study Duration

7-33 days

Participants

Adult GFAP–/–Vim–/– and age-matched WT female mice

Evidence Level

Not specified

Key Findings

1
GFAP–/–Vim–/– mice showed less removal of synaptic boutons from injured motoneurons compared to wild-type mice after axotomy.
2
Reinnervation of motor endplates was reduced in GFAP–/–Vim–/– mice 13 days after sciatic nerve crush, indicating delayed regeneration.
3
Functional recovery was delayed in GFAP–/–Vim–/– mice but ultimately reached completion, suggesting an impact on response dynamics rather than the final outcome.

Research Summary

The study investigates the role of GFAP and vimentin in nerve regeneration and synaptic stripping after sciatic nerve lesion in mice. Results showed reduced synaptic elimination, delayed reinnervation, and slowed functional recovery in GFAP–/–Vim–/– mice, indicating a role for these proteins in the dynamics of nerve regeneration. The absence of GFAP and vimentin affects the speed of the regenerative response without preventing complete recovery, highlighting different consequences of astrocyte reactivity in the peripheral versus central nervous systems.

Practical Implications

Therapeutic Modulation of Gliosis

The study suggests potential therapeutic strategies for modulating reactive gliosis to improve regenerative responses after nerve injury, though the effects may differ between the central and peripheral nervous systems.

Understanding Glial Cell Function

Further research is needed to elucidate the precise molecular mechanisms by which GFAP and vimentin influence glial cell behavior and their impact on nerve regeneration.

Targeted Therapies

Targeted therapies aimed at enhancing Schwann cell proliferation and axonal guidance could improve recovery outcomes after peripheral nerve injuries, especially in cases where glial cell function is compromised.

Study Limitations

1
The study was conducted on mice, and results may not be directly translatable to humans.
2
The specific types of synapses affected by the absence of GFAP and vimentin were not fully characterized.
3
The molecular mechanisms underlying the observed differences in nerve regeneration dynamics remain to be fully elucidated.

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