Postinjury Administration of 17b-Estradiol Induces Protection in the Gray and White Matter With Associated Functional Recovery After Cervical Spinal Cord Injury in Male Rats

The Journal of Comparative Neurology, 2012 · DOI: 10.1002/cne.23056 · Published: February 8, 2012

Spinal Cord Injury Endocrinology Neurology

Simple Explanation

This study investigates the potential therapeutic effects of 17b-estradiol, a form of estrogen, on spinal cord injuries (SCIs) in male rats. The researchers focused on cervical SCIs, which are common in humans and affect both gray and white matter in the spinal cord. Rats with cervical SCIs were treated with 17b-estradiol via slow-release pellets shortly after injury. The study then evaluated the effects of the treatment on various factors, including neuronal survival, inflammation, and functional recovery. The results indicated that 17b-estradiol could protect both the gray and white matter in the injured spinal cord. This treatment improved the rats' ability to perform skilled motor tasks, suggesting a clinically relevant protective effect.

Study Duration

7 weeks

Participants

60 adult male Sprague–Dawley rats

Evidence Level

Level II: Experimental study in animals

Key Findings

1
Post-SCI administration of 17b-estradiol decreased neuronal loss in the ventral horn, suggesting a neuroprotective effect.
2
Treatment with 17b-estradiol decreased reactive astrogliosis and the immune response, indicating reduced inflammation in the injured spinal cord.
3
Post-SCI administration of 17b-estradiol increased white matter sparing at the lesion epicenter, implying protection of the spinal cord's structural integrity.

Research Summary

This study aimed to evaluate the effects of post-SCI administration of 17b-estradiol on functional recovery and histopathology in a cervical model of SCI. The researchers found that post-SCI administration of 17b-estradiol decreased neuronal loss in the ventral horn, decreased reactive astrogliosis, decreased the immune response, and increased white mater sparing at the lesion epicenter. The findings suggest that post-SCI administration of 17b-estradiol protected both the gray and white matter in cervical SCI and improved function on skilled motor tasks.

Practical Implications

Potential Therapeutic Strategy

17b-estradiol is currently approved in several formulations for human use, translation of these findings into clinical trials may yield a promising novel treatment strategy for patients with both gray and white matter injury.

Clinical Relevance

The clinical relevance of this study stems both from the model used and the therapeutic evaluated; mimics the majority of clinical SCIs by including both gray and white matter pathophysiology.

Estrogen Receptor Mechanisms

Many aspects of estrogen-mediated protection (neuronal survival, reduction in gliosis, and inflammation) could be blocked by coadministration with the estrogen receptor antagonist, which suggests that this is an estrogen receptor-dependent mechanism.

Study Limitations

1
Large within-group variability in the animals’ performance was observed at multiple timepoints which potentially diluted possible treatment effects.
2
Study only used male rats, so the findings may not be generalizable to females.
3
The doses of 17b-estradiol evaluated are in a range that is supraphysiological

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