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INVITED REVIEW
Year : 2015  |  Volume : 10  |  Issue : 3  |  Page : 385-390

Tamoxifen and Src kinase inhibitors as neuroprotective/neuroregenerative drugs after spinal cord injury


1 Department of Physiology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936, USA
2 University of Puerto Rico Carolina Campus, Department of Natural Sciences, Carolina, PR 00984, USA

Correspondence Address:
Jorge D Miranda
Department of Physiology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR 00936
USA
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Source of Support: The project was partially supported by the MBRS-RISE Program (R25 GM061838) and COBRE (5P20-GM103642), Conflict of Interest: None


DOI: 10.4103/1673-5374.153685

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Spinal cord injury (SCI) is a devastating condition that produces significant changes in the lifestyle of patients. Many molecular and cellular events are triggered after the initial physical impact to the cord. Two major phases have been described in the field of SCI: an acute phase and late phase. Most of the therapeutic strategies are focused on the late phase because this provides an opportunity to target cellular events like apoptosis, demyelination, scar formation and axonal outgrowth. In this mini-review, we will focus on two agents (tamoxifen and a Src kinase family inhibitor known as PP2) that have been shown in our laboratory to produce neuroprotective (increase cell survival) and/or regenerative (axonal outgrowth) actions. The animal model used in our laboratory is adult female rat (~250 g) with a moderate contusion (12.5 mm) to the spinal cord at the T 10 level, using the MASCIS impactor device. Tamoxifen or PP2 was administered by implantation of a 15 mg pellet (Innovative Research of America, Sarasota, FL, USA) or by intraperitoneal injections (1.5 mg/kg, every 3 days), respectively, to produce a long-term effect (28 days). Tamoxifen and the Src kinase inhibitor, PP2, are drugs that in rats with a moderate spinal cord injury promote functional locomotor recovery, increase spared white matter tissue, and stimulate axonal outgrowth. Moreover, tamoxifen reduces the formation of reactive oxygen species. Therefore, these drugs are possible therapeutic agents that have a neuroprotective/regenerative activity in vertebrates with SCI.


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