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  4. Delayed post-injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice

Delayed post-injury administration of C5a improves regeneration and functional recovery after spinal cord injury in mice

Clinical and Experimental Immunology, 2013 · DOI: doi:10.1111/cei.12175 · Published: January 1, 2013

Spinal Cord InjuryImmunologyNeurology

Simple Explanation

The complement system, part of the immune system, can worsen spinal cord injury (SCI). However, recent studies suggest it might also have protective effects, with C5a being a key factor. This study investigates the potential neuroprotective effect of C5a after SCI. The study found that administering C5a 24 hours after SCI in mice improved locomotor function. In vitro experiments showed C5a could prevent nerve cell death (apoptosis) and promote nerve fiber growth. These results suggest C5a has dual roles after SCI, depending on the timing and concentration. This must be considered when using treatments to block complement activation to help regeneration after SCI.

Study Duration
9 weeks
Participants
Female wild-type C57/BL6 mice (weighing 18–20 g, 6–8 weeks old)
Evidence Level
Level 2: Experimental study in mice

Key Findings

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    Delayed administration of C5a (24 hours post-injury) significantly improved locomotor function in mice after SCI.
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    In vitro, C5a inhibited caspase-3-mediated neuronal apoptosis at concentrations of 50–100 nM.
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    C5a promoted neurite outgrowth of uninjured neurons in vitro.

Research Summary

This study investigates the neuroprotective effects of C5a after spinal cord injury (SCI). It examines the impact of C5a administration at different time points relative to the injury, both in vivo and in vitro. The results indicate that while C5a administration before or immediately after SCI exacerbates inflammation and impairs recovery, delayed administration (24 hours post-injury) improves locomotor function and reduces tissue damage. The study also demonstrates that C5a can inhibit neuronal apoptosis and promote neurite outgrowth in vitro, suggesting a concentration- and time-dependent neuroprotective role.

Practical Implications

Therapeutic Timing

The timing of C5a administration is crucial. Delayed administration post-injury may be beneficial, while early administration could be detrimental.

Concentration-Dependent Effects

The concentration of C5a should be carefully controlled to maximize its neuroprotective effects and minimize potential inflammatory responses.

Targeted Therapies

Developing targeted therapies that modulate C5a activity at specific time points after SCI could improve outcomes.

Study Limitations

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