Salidroside promotes the repair of spinal cord injury by inhibiting astrocyte polarization, promoting neural stem cell proliferation and neuronal differentiation

Cell Death Discovery, 2024 · DOI: https://doi.org/10.1038/s41420-024-01989-2 · Published: April 24, 2024

Spinal Cord Injury Pharmacology Regenerative Medicine

Simple Explanation

Spinal cord injury (SCI) is a challenging condition with limited effective treatments. After SCI, neural stem cells (NSCs) move to the injury site, potentially aiding nerve regeneration, but this process isn't fully effective. Salidroside, a compound with pro-repair qualities, has shown promise in treating conditions like arthritis and cerebral ischemia, and in reducing early inflammation after SCI. This study explores salidroside's role in the later stages of SCI repair. The study found that salidroside treatment in mice with SCI improved motor function, stimulated nerve regeneration and remyelination, reduced glial scar formation, decreased the activation of harmful astrocytes, and promoted NSC migration to the injury site.

Study Duration

28 days

Participants

45 female C57BL/6J mice (18–35 g; 8 weeks old)

Evidence Level

Not specified

Key Findings

1
Salidroside enhances functional recovery in SCI mice by promoting axonal regeneration, myelin reconstitution, and inhibiting glial scar formation and the activation of neurotoxic A1 astrocytes.
2
Salidroside inhibits astrocyte proliferation and A1 polarization in vitro.
3
Neurotoxic astrocytes suppress NSC proliferation and induce their differentiation into astrocytes, facilitated by the activation of c-Jun N-terminal kinase (JNK) and signal transducer and activator of transcription 3 (STAT3) pathways; salidroside can restrain this.

Research Summary

This study investigates the therapeutic potential of salidroside in treating spinal cord injury (SCI). The research focuses on salidroside's impact on nerve regeneration, glial scar formation, astrocyte polarization, and neural stem cell (NSC) behavior in SCI mice. The findings indicate that salidroside treatment improves motor function, promotes nerve regeneration and remyelination, reduces glial scar formation, inhibits the activation of neurotoxic astrocytes, and facilitates NSC migration to the injured region. In vitro experiments reveal that salidroside inhibits astrocyte proliferation and A1 polarization, and ameliorates the suppression of NSC proliferation by diminishing JNK pathway phosphorylation and restoring their differentiation into neurons by suppressing the STAT3 pathway.

Practical Implications

Therapeutic Agent for SCI

Salidroside shows promise as a therapeutic agent for traumatic SCI treatment, enhancing neural regeneration.

Targeting Astrocytes and NSCs

Salidroside's ability to modulate astrocyte polarization and NSC fate suggests potential strategies for improving the spinal cord microenvironment.

Combination Therapy Potential

Salidroside may be used as an adjunctive therapy for stem cell transplantation to enhance functional recovery.

Study Limitations

1
Extrapolating in vitro results to in vivo experiments can be challenging due to complex signal networks and intercellular interactions.
2
The regulatory effect of salidroside on SCI through peripheral pathways, potentially affecting innate and adaptive immunity.
3
The efficiency of salidroside crossing the blood-brain barrier is a concern; repair of the blood-brain barrier may reduce salidroside efficacy, while overdosage can increase the risk of organ toxicity.

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