Teriparatide mitigates oxidative stress following spinal cord injury and enhances neurological recovery via the Nrf2/HO-1 signaling pathway

Frontiers in Pharmacology, 2025 · DOI: 10.3389/fphar.2025.1538857 · Published: March 19, 2025

Spinal Cord Injury Pharmacology Genetics

Simple Explanation

Spinal cord injury (SCI) can lead to oxidative stress, which worsens the damage. This study explores if teriparatide, a drug used for osteoporosis, can help reduce this stress and improve recovery in rats with SCI. The research found that teriparatide treatment improved motor function and reduced oxidative stress markers in the injured spinal cords of rats. The drug appears to work by activating the Nrf2/HO-1 pathway, which boosts antioxidant production in the body.

Study Duration

14 days

Participants

138 male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Teriparatide treatment significantly enhanced motor function recovery post-SCI in rats, as assessed by open field tests and BBB scoring.
2
Teriparatide upregulated Nrf2 expression, leading to increased production of antioxidant proteins HO-1 and SOD2, reduced MDA levels, and boosted GSH-PX activity in spinal tissues.
3
Inhibition of Nrf2 with ML385 attenuated the beneficial effects of teriparatide, suggesting that the Nrf2/HO-1 pathway is crucial for its neuroprotective action.

Research Summary

The study investigates the therapeutic effects of teriparatide in a rat model of SCI, focusing on its ability to mitigate oxidative stress and improve neurological recovery. Results demonstrate that teriparatide enhances motor and exploratory functions, increases GSH-PX activity, and reduces MDA levels post-injury. The underlying mechanism involves the activation of the Nrf2/HO-1 pathway, leading to increased production of antioxidant proteins HO-1 and SOD2, which collectively contribute to neuroprotection.

Practical Implications

Clinical Translation

Repurposing an FDA-approved osteoporosis drug presents a clinically translatable strategy for neuroprotection in SCI patients.

Therapeutic Target

The Nrf2/HO-1 pathway is identified as a key therapeutic target for mitigating oxidative damage and promoting recovery in SCI.

Novel Approach

This study introduces a novel pharmacological approach for SCI management by leveraging the antioxidant properties of teriparatide.

Study Limitations

1
The study primarily focused on the Nrf2/HO-1 pathway, but other pathways like FoxO and NF-κB may also play a role in oxidative stress regulation.
2
Further transcriptomic studies are needed to identify additional pathways influenced by teriparatide.
3
The study was conducted on rats and may not fully translate to human physiology.

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