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2
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3
The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery.脊髓损伤后给予磷酸二酯酶抑制剂咯利普兰可促进轴突再生和功能恢复。
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Systemic administration of rolipram increases medullary and spinal cAMP and activates a latent respiratory motor pathway after high cervical spinal cord injury.咯利普兰的全身给药可增加延髓和脊髓中的环磷酸腺苷(cAMP),并在高位颈脊髓损伤后激活一条潜在的呼吸运动通路。
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本文引用的文献

1
Nanofibrous Patches for Spinal Cord Regeneration.用于脊髓再生的纳米纤维贴片
Adv Funct Mater. 2010 May 10;20(9):1433-1440. doi: 10.1002/adfm.200901889. Epub 2010 Mar 17.
2
Prenatal repair of myelomeningocele with aligned nanofibrous scaffolds-a pilot study in sheep.产前修复脊髓脊膜膨出症的对齐纳米纤维支架 - 羊的初步研究。
J Pediatr Surg. 2011 Dec;46(12):2279-83. doi: 10.1016/j.jpedsurg.2011.09.014.
3
Induced pluripotent stem cells for neural tissue engineering.诱导多能干细胞在神经组织工程中的应用。
Biomaterials. 2011 Aug;32(22):5023-32. doi: 10.1016/j.biomaterials.2011.03.070. Epub 2011 Apr 22.
4
Engineering bi-layer nanofibrous conduits for peripheral nerve regeneration.工程化双层纳米纤维导管用于周围神经再生。
Tissue Eng Part C Methods. 2011 Jul;17(7):705-15. doi: 10.1089/ten.tec.2010.0565. Epub 2011 Apr 18.
5
A randomized trial of prenatal versus postnatal repair of myelomeningocele.随机试验:产前与产后修复脊髓脊膜膨出。
N Engl J Med. 2011 Mar 17;364(11):993-1004. doi: 10.1056/NEJMoa1014379. Epub 2011 Feb 9.
6
A re-assessment of a combinatorial treatment involving Schwann cell transplants and elevation of cyclic AMP on recovery of motor function following thoracic spinal cord injury in rats.一项关于组合治疗的重新评估,该治疗涉及雪旺细胞移植和升高环腺苷酸,以恢复大鼠胸段脊髓损伤后的运动功能。
Exp Neurol. 2012 Feb;233(2):625-44. doi: 10.1016/j.expneurol.2010.12.020. Epub 2010 Dec 30.
7
Glial restricted precursor cell transplant with cyclic adenosine monophosphate improved some autonomic functions but resulted in a reduced graft size after spinal cord contusion injury in rats.胶质限制前体细胞移植联合环磷酸腺苷可改善一些自主功能,但会导致大鼠脊髓挫伤损伤后移植物体积减小。
Exp Neurol. 2011 Jan;227(1):159-71. doi: 10.1016/j.expneurol.2010.10.011. Epub 2010 Oct 30.
8
A combination immunomodulatory treatment promotes neuroprotection and locomotor recovery after contusion SCI.联合免疫调节疗法可促进挫伤性 SCI 后的神经保护和运动功能恢复。
Exp Neurol. 2011 Jul;230(1):3-15. doi: 10.1016/j.expneurol.2010.03.010. Epub 2010 Mar 23.
9
Effects of rolipram on adult rat oligodendrocytes and functional recovery after contusive cervical spinal cord injury.罗利普兰对成年大鼠少突胶质细胞的影响及对挫伤性颈髓损伤后功能恢复的作用。
Neuroscience. 2009 Nov 10;163(4):985-90. doi: 10.1016/j.neuroscience.2009.07.039. Epub 2009 Jul 25.
10
A new rating scale for open-field evaluation of behavioral recovery after cervical spinal cord injury in rats.一种用于评估大鼠颈脊髓损伤后行为恢复的新旷场评价量表。
J Neurotrauma. 2009 Jul;26(7):1043-53. doi: 10.1089/neu.2008.0717.

用于脊髓修复中罗利普兰局部递送的载药微纤维贴剂。

Drug-eluting microfibrous patches for the local delivery of rolipram in spinal cord repair.

机构信息

UC Berkeley & UCSF Joint Graduate Program in Bioengineering, Berkeley/San Francisco, CA, USA.

出版信息

J Control Release. 2012 Aug 10;161(3):910-7. doi: 10.1016/j.jconrel.2012.05.034. Epub 2012 May 23.

DOI:10.1016/j.jconrel.2012.05.034
PMID:22634093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3698241/
Abstract

Spinal cord injury (SCI) remains a major challenge for regenerative medicine. Following SCI, axon growth inhibitors and other inflammatory responses prevent functional recovery. Previous studies have demonstrated that rolipram, an anti-inflammatory and cyclic adenosine monophosphate preserving small molecule, improves spinal cord regeneration when delivered systemically. However, more recent studies showed that rolipram has some adverse effects in spinal cord repair. Here, we developed a drug-delivery platform for the local delivery of rolipram into the spinal cord. The potential of drug-eluting microfibrous patches for continuous delivery of high and low-dose rolipram concentrations was characterized in vitro. Following C5 hemisections, athymic rats were treated with patches loaded with low and high doses of rolipram. In general, animals treated with low-dose rolipram experienced greater functional and anatomical recovery relative to all other groups. Outcomes from the high-dose rolipram treatment were similar to those with no treatment. In addition, high-dose treated animals experienced reduced survival rates suggesting that systemic toxicity was reached. With the ability to control the release of drug dosage locally within the spinal cord, drug-eluting microfibrous patches demonstrate the importance of appropriate local release-kinetics of rolipram, proving their usefulness as a therapeutic platform for the study and repair of SCI.

摘要

脊髓损伤 (SCI) 仍然是再生医学的一大挑战。SCI 后,轴突生长抑制剂和其他炎症反应阻止了功能恢复。先前的研究表明,罗利普兰是一种抗炎和环磷酸腺苷保护的小分子,当全身给药时,可改善脊髓再生。然而,最近的研究表明,罗利普兰在脊髓修复中有一些不良反应。在这里,我们开发了一种用于将罗利普兰局部递送到脊髓的药物输送平台。体外研究了载药微纤维贴片持续输送高剂量和低剂量罗利普兰的潜力。在 C5 半切术后,对载有低剂量和高剂量罗利普兰的贴片进行了无胸腺大鼠的治疗。一般来说,与其他所有组相比,低剂量罗利普兰治疗的动物经历了更大的功能和解剖学恢复。高剂量罗利普兰治疗的结果与无治疗的结果相似。此外,高剂量治疗的动物存活率降低,表明已达到全身毒性。通过能够在脊髓内局部控制药物剂量的释放,载药微纤维贴片证明了罗利普兰适当的局部释放动力学的重要性,证明了它们作为 SCI 研究和修复的治疗平台的有用性。