Tamoxifen attenuates inflammatory-mediated damage and improves functional outcome after spinal cord injury in rats
Abstract
Tamoxifen has been found to be neuroprotective in both transient and permanent experimental ischemic stroke. However, it remains unknown whether this agent shows a similar beneficial effect after spinal cord injury (SCI), and what are its underlying mechanisms. In this study, we investigated the efficacy of tamoxifen treatment in attenuating SCI-induced pathology. Blood-spinal cord barrier (BSCB) permeability, tissue edema formation, microglial activation, neuronal cell death and myelin loss were determined in rats subjected to spinal cord contusion. The results showed that tamoxifen, administered at 30 min post-injury, significantly decreased interleukin-1beta (IL-1beta) production induced by microglial activation, alleviated the amount of Evans blue leakage and edema formation. In addition, tamoxifen treatment clearly reduced the number of apoptotic neurons post-SCI. The myelin loss and the increase in production of myelin-associated axonal growth inhibitors were also found to be significantly attenuated at day 3 post-injury. Furthermore, rats treated with tamoxifen scored much higher on the locomotor rating scale after SCI than did vehicle-treated rats, suggesting improved functional outcome after SCI. Together, these results demonstrate that tamoxifen provides neuroprotective effects for treatment of SCI-related pathology and disability, and is therefore a potential neuroprotectant for human spinal cord injury therapy.
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Tamoxifen administration immediately after SCI reduces this response in part by promoting cell survival.
“Studies have shown that tamoxifen administration immediately after SCI reduces this response in part by promoting cell survival [39, 41, 55].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [41]
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 [41]
These results contradict other CNS trauma studies that show tamoxifen improves anatomical and motor recovery in female and male SCI rodents.
“These results contradict other CNS trauma studies that show tamoxifen improves anatomical and motor recovery in female and male SCI rodents [39–41, 55], but this is likely attributed to differences in the timing of dosing.”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [41]
Previous studies began tamoxifen treatment within 24 hours of injury, then gave low doses of tamoxifen chronically via intraperitoneal injection or intrathecal infusion.
“Previous studies began tamoxifen treatment within 24 hours of injury, then gave low doses of tamoxifen chronically via intraperitoneal injection [39, 41] or intrathecal infusion [40, 55].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [41]
This is opposite of previous reports that suggest tamoxifen is neuroprotective and increases neuron survival.
“This is opposite of previous reports that suggest tamoxifen is neuroprotective and increases neuron survival [39, 41, 42, 55].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [41]
Studies that report a neuroprotective effect of tamoxifen have given it during the acute phase, capitalizing on tamoxifen's ability to reduce inflammation, decrease glial reactivity, and promote cell survival.
“Studies that report a neuroprotective effect of tamoxifen have given it during this acute phase, capitalizing on tamoxifen’s ability to reduce inflammation, decrease glial reactivity, and promote cell survival [39–42, 55].”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [41]
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- Authors
- Tian, D., Liu, J., Xie, M., Zhan, Y., Qu, W., Yu, Z., Tang, Z., Pan, D., & Wang, W.
- Affiliations
- Tongji Hospital (CN)
- Corresponding author
- Wang, Wei
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2009-05-21
- Volume
- 109
- Issue
- 6
- Pages
- 1658-1667
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W1982466660
- Cited by
- 98
- References
- 0
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 10 · 2015: 8 · 2014: 12 · 2013: 5 · 2012: 10
- FWCI
- 6.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- tamoxifen, spinal cord injury, neuroprotection, spinal cord contusion, blood-spinal cord barrier permeability, microglial activation, IL-1β, neuronal apoptosis, demyelination, tissue edema, locomotor recovery, anti-inflammatory therapy
- MeSH terms
- Nogo Proteins, Animals, Behavior, Animal, Blood-Brain Barrier, Disease Models, Animal, Double-Blind Method, Edema, Estrogen Antagonists, Gene Expression Regulation, Indoles, Inflammation, Male, Myelin Proteins, Myelin Sheath, Peptide Fragments, Phosphopyruvate Hydratase, Spinal Cord Injuries, Tamoxifen, Time Factors, Rats, Sprague-Dawley, Apoptosis, Myelin-Associated Glycoprotein, Recovery of Function, In Situ Nick-End Labeling, CD11b Antigen, Rats, Interleukin-1beta
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