The cancer drug tamoxifen: A potential therapeutic treatment for spinal cord injury
Open accessAbstract
Tamoxifen (TMX) is a selective estrogen receptor modulator that can mimic the neuroprotective effects of estrogen but lacks its systemic adverse effects. We found that TMX (1 mg/day) significantly improved the motor recovery of partially paralyzed hind limbs of male adult rats with thoracic spinal cord injury (SCI), thus indicating a translational potential for this cancer medication given its clinical safety and applicability and the lack of currently available treatments for SCI. To shed light on the mechanisms underlying the beneficial effects of TMX for SCI, we used proteomic analyses, Western blots and histological assays, which showed that TMX treatment spared mature oligodendrocytes/increased myelin levels and altered reactive astrocytes, including the upregulation of the water channels aquaporin 4 (AQP4), a novel finding. AQP4 increases in TMX-treated SCI rats were associated with smaller fluid-filled cavities with borders consisting of densely packed AQP4-expressing astrocytes that closely resemble the organization of normal glia limitans externa (in contrast to large cavities in control SCI rats that lacked glia limitans-like borders and contained reactive glial cells). Based on our findings, we propose that TMX is a promising candidate for the therapeutic treatment of SCI and a possible intervention for other neuropathological conditions associated with demyelination and AQP4 dysfunction.
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21 days of tamoxifen treatment beginning immediately after SCI reduced inflammation, decreased glial reactivity, promoted cell survival, increased white matter sparing, and enhanced functional recovery in rats and cats.
“21 days of tamoxifen treatment beginning immediately after SCI reduced inflammation, decreased glial reactivity, promoted cell survival, increased white matter sparing, and enhanced functional recovery in rats and cats [38–43].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [43]
Tamoxifen is a known repressor of astrocyte reactivity acutely after SCI.
“Tamoxifen is a known repressor of astrocyte reactivity acutely after SCI [42, 43, 55].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [43]
If tamoxifen treatment was delayed until 42 days after SCI, hindlimb motor recovery was not changed.
“if tamoxifen treatment was delayed until 42 days after SCI, then hindlimb motor recovery was not changed; the impact of delayed tamoxifen treatment on tissue repair was not assessed [43].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [43]
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- Authors
- Guptarak, J., Wiktorowicz, J. E., Sadygov, R. G., Zivadinovic, D., Paulucci-Holthauzen, A. A., Vergara, L., & Nesic, O.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- University of Texas Medical Branch
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 2014-02
- Volume
- 31
- Issue
- 3
- Pages
- 268-283
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- PMC
- PMC3904530
- OpenAlex
- W1965323887
- Cited by
- 38
- References
- 72
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 9 · 2015: 5 · 2014: 2
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neurotrauma (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eCommons - AKU (Aga Khan University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- tamoxifen, spinal cord injury, selective estrogen receptor modulators, motor recovery, oligodendrocytes, myelin, reactive astrocytes, aquaporin-4, demyelination, hindlimb paralysis, neuroprotection
- MeSH terms
- Animals, Brain, Fluorescent Antibody Technique, Male, Spinal Cord Injuries, Tamoxifen, Blotting, Western, Rats, Sprague-Dawley, Neuroprotective Agents, Recovery of Function, Proteomics, Rats, Aquaporin 4
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