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急性剂量依赖性聚(普瑞巴林)对小鼠脊髓挫伤模型的神经保护作用。

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

机构信息

Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th Street, Troy, New York 12180, United States.

Center for Brain and Spinal Cord Repair, Department of Neuroscience, The Ohio State University, 460 West 12th Avenue, Columbus, Ohio 43210, United States.

出版信息

ACS Chem Neurosci. 2021 Mar 17;12(6):959-965. doi: 10.1021/acschemneuro.0c00798. Epub 2021 Feb 26.

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.

摘要

17β-雌二醇(E2)在全身给予时可在脊髓损伤的临床前模型中提供神经保护。本研究的目的是使用聚(原 E2)膜生物材料将 E2 局部应用于损伤的脊髓,以持续一段时间。在成年雄性小鼠的压迫性脊髓损伤后,将聚(原 E2)膜植入硬脑膜下,并在损伤和植入后 7 天通过免疫组织化学评估神经保护作用。在这些研究中,与受伤对照相比,聚(原 E2)膜适度改善了神经保护作用,而不影响炎症反应。为了增加释放的 E2 剂量,通过将未结合的 E2 掺入聚(原 E2)膜中,制备了突释释放聚(原 E2)膜。然而,与受伤对照相比,突释释放聚(原 E2)膜在损伤后 7 天或 21 天都没有显著增强神经保护作用或限制炎症。未来的工作将集中于开发能够更精确地释放治疗剂量 E2 的聚(原 E2)生物材料。

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