title: Tamoxifen Administration Immediately or 24 Hours after Spinal Cord Injury Improves Locomotor Recovery and Reduces Secondary Damage in Female Rats.
abstract: 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. TAM-treated 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.
authors.affiliation: 1 Department of Physiology, University of Puerto Rico Medical Sciences Campus , San Juan, Puerto Rico .
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Colón
authors.affiliation: 1 Department of Physiology, University of Puerto Rico Medical Sciences Campus , San Juan, Puerto Rico .
authors.forename: Aranza I
authors.initials: AI
authors.lastname: Torrado
authors.affiliation: 2 Department of Biology, University of Puerto Rico Rio Piedras Campus , San Juan, Puerto Rico .
authors.forename: Ámbar
authors.initials: Á
authors.lastname: Cajigas
authors.affiliation: 3 Department of Natural Sciences, University of Puerto Rico Carolina Campus , Carolina, Puerto Rico .
authors.forename: José M
authors.initials: JM
authors.lastname: Santiago
authors.affiliation: 1 Department of Physiology, University of Puerto Rico Medical Sciences Campus , San Juan, Puerto Rico .
authors.forename: Iris K
authors.initials: IK
authors.lastname: Salgado
authors.affiliation: 3 Department of Natural Sciences, University of Puerto Rico Carolina Campus , Carolina, Puerto Rico .
authors.forename: Yaría
authors.initials: Y
authors.lastname: Arroyo
authors.affiliation: 1 Department of Physiology, University of Puerto Rico Medical Sciences Campus , San Juan, Puerto Rico .
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Miranda
mesh_terms: D000818:Animals; D005260:Female; D008124:Locomotion / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D013629:Tamoxifen
keywords: astrogliosis; neuroprotection; selective estrogen receptor modulator (SERM); spare tissue; therapeutic drug