Neuroprotective effects of tamoxifen on experimental spinal cord injury in rats

İsmailoğlu, Özgür; Oral, Baha; Görgülü, Adnan; Sütçü, Recep; Demır, Necdet

doi:10.1016/j.jocn.2010.01.049

Cited by 34 publications

(22 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the expected effects of TAM are reduction of inflammatory cytokines, microglial activation, and reduction in astrogliosis, as has been shown by others in models of SCI 12,14,17,18 and brain ischemia or trauma. 8,13,16,[44][45][46][47][48] Administration of TAM, 30 min after spinal cord contusion, attenuates neuronal apoptosis within the first few days, 12 possibly through the inactivation of caspase-3.…”

Section: Discussionmentioning

confidence: 56%

“…The dose of TAM used in this study (0.71 mg/d) is lower than those used by others with neuroprotective effects after SCI (1 mg/d), 12,14,15,17,18 but as mentioned by Guptarak and colleagues, 14 still within the range used to manage other conditions. 54 Because all studies with TAM after SCI were made in male rats, the novelties of these findings were the inclusion and analysis of this drug in female vertebrates, as well as the therapeutic window that produced some functional locomotor recovery after trauma using a low dose of TAM.…”

mentioning

confidence: 74%

See 1 more Smart Citation

Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats

Colón

Torrado

Cajigas

et al. 2016

Journal of Neurotrauma

View full text Add to dashboard Cite

Spinal cord injury (SCI) is a condition with no available cure. The initial physical impact triggers a cascade of molecular and cellular events that generate a nonpermissive environment for cell survival and axonal regeneration. Spinal cord injured patients often arrive at the clinic hours after the initial insult. This indicates the need to study and develop treatments with a long therapeutic window of action and multiactive properties, which target the complex set of events that arise after the initial trauma. We provide evidence that tamoxifen (TAM), a drug approved by the Food and Drug Administration, exerts neuroprotective effects in an animal model when applied up-to 24 h after SCI. We hypothesized that continuous TAM administration will improve functional locomotor recovery by favoring myelin preservation and reducing secondary damage after SCI. Adult female Sprague-Dawley rats (*230 g) received a moderate contusion to the thoracic (T9-T10) spinal cord, using the MASCIS impactor device. To determine the therapeutic window available for TAM treatment, rats were implanted with TAM pellets (15 mg) immediately or 24 h after SCI. Locomotor function (Basso, Beattie, Bresnahan open field test, grid walk, and beam crossing tests) was assessed weekly for 35 days post-injury. TAMtreated rats showed significant functional locomotor recovery and improved fine movements when treated immediately or 24 h after SCI. Further, TAM increased white matter preservation and reduced secondary damage caused by astrogliosis, axonal degeneration, and cell death after trauma. These results provide evidence for TAM as a potential therapeutic agent to treat SCI up to 24 h after the trauma.

show abstract

Section: Discussionmentioning

confidence: 56%

mentioning

confidence: 74%

Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats

Colón

Torrado

Cajigas

et al. 2016

Journal of Neurotrauma

View full text Add to dashboard Cite

show abstract

“…and several types of traumatic injuries(Franco Rodriguez et al, 2013;Guptarak et al, 2014;Ismailoglu et al, 2010;Mosquera et al, 2014;Tian et al, 2009).Interestingly, SERMs also reduce gliosis and neuroinflammation. Tamoxifen and raloxifene decrease microglia activation in the cerebellum after systemic LPS administration(Tapia- Gonzalez et al, 2008) and in the hippocampus after a penetrating brain injury(Barreto et al, 2014); they also decrease the expression of proinflammatory molecules by microglia cell lines and primary cultures of microglia(Ishihara et al, 2015;Suuronen et al, 2005).…”

mentioning

confidence: 99%

Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions

Acaz‐Fonseca

Ávila-Rodriguez

Garcia-Segura

et al. 2016

Progress in Neurobiology

105

View full text Add to dashboard Cite

“…To date, the major clinical applications of SERMs are in the treatment of ER-positive breast cancer and the prevention and treatment of postmenopausal symptoms caused by the low levels of estrogens that accompany osteoporosis (1)(2)(3). In addition, recent studies suggest the possible use of SERMs as neuroprotective agents (4,5).…”

Section: Introductionmentioning

confidence: 99%

NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity

Kim

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Estrogens act through interactions with estrogen receptors (ERs) to play diverse roles in various pathophysiological conditions. A number of synthetic selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene, have been developed and used to treat ER-related diseases, including breast cancer and osteoporosis. Here, we identified a novel compound, bis(4-hydroxyphenyl) methanone-O-isopentyl oxime, designated NJK14013, as an ER agonist. NJK14013 activated ER-dependent transcription in a concentration-dependent manner, while suppressing androgen receptor-dependent transcriptional activity. It induced the activation-related phosphorylation of ER and enhanced the transcription of growth regulation by estrogen in breast cancer 1 (GREB1), further supporting its ER-stimulating activity. NJK14013 exerted anti-proliferative effects on various cancer cell lines, including an ER-negative breast cancer cell line, suggesting that it is capable of suppressing the growth of cancer cells independent of its ER-modulating activity. In addition, NJK14013 treatment resulted in significant apoptotic death of MCF7 and Ishikawa cancer cells, but did not induce apoptosis in non-cancer human umbilical vein endothelial cells. Collectively, our findings demonstrate that NJK14013 is a novel SERM that can activate ER-mediated transcription in MCF7 cells and suppress the proliferation of various cancer cells, including breast cancer cells and endometrial cancer cells. These results suggest that NJK14013 has potential as a novel SERM for anticancer or hormone-replacement therapy with reduced risk of carcinogenesis.

show abstract

Neuroprotective effects of tamoxifen on experimental spinal cord injury in rats

Cited by 34 publications

References 19 publications

Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats

Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats

Regulation of astroglia by gonadal steroid hormones under physiological and pathological conditions

NJK14013, a novel synthetic estrogen receptor-α agonist, exhibits estrogen receptor-independent, tumor cell-specific cytotoxicity

Contact Info

Product

Resources

About