Tamoxifen Promotes Axonal Preservation and Gait Locomotion Recovery after Spinal Cord Injury in Cats
Open accessAbstract
We performed experiments in cats with a spinal cord penetrating hemisection at T13-L1 level, with and without tamoxifen treatment. The results showed that the numbers of the ipsilateral and contralateral ventral horn neurons were reduced to less than half in the nontreated animals compared with the treated ones. Also, axons myelin sheet was preserved to almost normal values in treated cats. On the contrary, in the untreated animals, their myelin sheet was reduced to 28% at 30 days after injury (DAI), in both the ipsilateral and contralateral regions of the spinal cord. Additionally, we made hindlimb kinematics experiments to study the effects of tamoxifen on cat locomotion after the injury: at 4, 16, and 30 DAI. We observed that the ipsilateral hindlimb angular displacement (AD) of the pendulum-like movements (PLM) during gait locomotion was recovered to almost normal values in treated cats. Contralateral PLM acquired similar values to those obtained in intact cats. At 4 DAI, untreated animals showed a compensatory increment of PLM occurring in the contralateral hindlimb, which was partially recovered at 30 DAI. Our findings indicate that tamoxifen exerts a neuroprotective effect and preserves or produces myelinated axons, which could benefit the locomotion recovery in injured cats.
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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 [39]
Methods (§2.2) says the cats received tamoxifen on days 0, 1, and 2 after injury, not for 21 days. Results (§§3.3–3.5) support neuronal and myelin preservation and improved gait in cats; the Discussion (§4) reports anti-inflammatory effects in rats from earlier work. This paper does not establish reduced glial reactivity or increased white matter sparing after the stated 21-day regimen in rats and cats. (LLM, conf=0.90)
Experimental — accuracy not yet measuredTamoxifen 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 [39]
The Methods (§2.2; page unavailable) report tamoxifen treatment beginning on the day of injury, and the Results (§3.4; page unavailable) report increased neuronal survival in treated cats. The Introduction describes tamoxifen as a proposed inflammatory-response modulator, but this study does not show that promoting cell survival is how it reduces that response. (LLM, conf=0.84)
Experimental — accuracy not yet measuredPrevious 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 [39]
Methods §2.2 reports tamoxifen at 1 mg/kg by intraperitoneal injection on days 0, 1, and 2 after injury, supporting early treatment and the route attributed to this source. It describes only a three-day course, not chronic treatment. The sentence assigns intrathecal infusion to other citations. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThese 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 [39]
The Introduction and Discussion report beneficial effects of tamoxifen in rats after spinal cord injury, and the Conclusions describe earlier positive neuroprotective effects in rodents. But this paper’s own anatomical and gait-recovery findings are from cats; our copy does not establish those combined outcomes in both female and male SCI rodents. No page numbers were provided for these passages. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThis 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 [39]
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 [39]
It is possible that giving tamoxifen at 300 mg/kg, compared to 1 mg/kg, was toxic and induced neuronal cell death.
“Tamoxifen is known to be toxic to humans and rodents at high doses [72–74]; therefore, it is possible that giving tamoxifen at 300 mg/kg, compared to 1 mg/kg [39, 55], was toxic and induced neuronal cell death.”
From Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury (2020) · cites this paper as [39]
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Pukos, N., & McTigue, D. M. (2020) · PLOS ONE · doi:10.1371/journal.pone.0235232 · Cited by 9 · see citing works
- Authors
- de la Torre Valdovinos, B., Duenas Jimenez, J. M., Estrada, I. J., Banuelos Pineda, J., Franco Rodriguez, N. E., Lopez Ruiz, J. R., Osuna Carrasco, L. P., Candanedo Arellano, A., & Duenas Jimenez, S. H.
- Affiliations
- Department of Computer Science, CUCEI, Universidad de Guadalajara, Avenida Revolucion No. 1500 Building M, Laboratory 212, 44430 Guadalajara, JAL, Mexico
- Department of Physiology, CUCS Universidad de Guadalajara, Sierra Mojada 950, Building P Third Floor, 44290 Guadalajara, JAL, Mexico
- Department of Physiology Biophysics and Neurosciences, Centro de Investigacion y Estudios Avanzados IPN, Avenida Instituto Politecnico Nacional 2508, 07360 Mexico City, DF, Mexico
- Department of Veterinary and Medicine, CUCBA Universidad de Guadalajara, Camino Ing. Ramon Padilla Sanchez 2100, 45110 Zapopan, JAL, Mexico
- Department of Neuroscience, CUCS Universidad de Guadalajara, Sierra Mojada 950, Building P Third Floor, 44290 Guadalajara, JAL, Mexico
- Venue
- Journal of Veterinary Medicine
- Publisher
- Wiley
- Published
- 2016-02-23
- Volume
- 2016
- Pages
- 1-16
- ISSN
- 2314-6966 (ISSN-L)
- 2356-7708
- PMC
- PMC4781988
- OpenAlex
- W2286893582
- Cited by
- 16
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2021: 2 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 2
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of Veterinary Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Universidad de Guadalajara
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
- Health Sciences › Veterinary › Small Animals › Veterinary Orthopedics and Neurology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- tamoxifen, spinal cord injury, myelination, neuroprotection, locomotor recovery, ventral horn neurons, hindlimb kinematics, cats, hemisection
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