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Acute Dose-Dependent Neuroprotective Effects of Poly(pro-17β-estradiol) in a Mouse Model of Spinal Contusion Injury.

Abstract
17β-Estradiol (E2) confers neuroprotection in preclinical models of spinal cord injury when administered systemically. The goal of this study was to apply E2 locally to the injured spinal cord for a sustained duration using poly(pro-E2) film biomaterials. Following contusive spinal cord injury in adult male mice, poly(pro-E2) films were implanted subdurally and neuroprotection was assessed using immunohistochemistry 7 days after injury and implantation. In these studies, poly(pro-E2) films modestly improved neuroprotection without affecting the inflammatory response when compared to the injured controls. To increase the E2 dose released, bolus-releasing poly(pro-E2) films were fabricated by incorporating unbound E2 into the poly(pro-E2) films. However, compared to the injured controls, bolus-releasing poly(pro-E2) films did not significantly enhance neuroprotection or limit inflammation at either 7 or 21 days post-injury. Future work will focus on developing poly(pro-E2) biomaterials capable of more precisely releasing therapeutic doses of E2.
AuthorsManoj K Gottipati, Samuel A T Ellman, Devan L Puhl, Zhen Guan, Phillip G Popovich, Edmund F Palermo, Ryan J Gilbert
JournalACS chemical neuroscience (ACS Chem Neurosci) Vol. 12 Issue 6 Pg. 959-965 (03 17 2021) ISSN: 1948-7193 [Electronic] United States
PMID33635633 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Neuroprotective Agents
  • Estradiol
Topics
  • Animals
  • Contusions
  • Estradiol
  • Male
  • Mice
  • Neuroprotective Agents (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries (drug therapy)

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