对紫杉醇在大鼠脊髓损伤模型中的解剖学和行为学效应进行独立评估。
Independent evaluation of the anatomical and behavioral effects of Taxol in rat models of spinal cord injury.
作者信息
Popovich Phillip G, Tovar C Amy, Lemeshow Stanley, Yin Qin, Jakeman Lyn B
机构信息
Center for Brain and Spinal Cord Repair, USA; Department of Neuroscience, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Center for Brain and Spinal Cord Repair, USA; Department of Neuroscience, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
出版信息
Exp Neurol. 2014 Nov;261:97-108. doi: 10.1016/j.expneurol.2014.06.020. Epub 2014 Jul 3.
Abstract
The goal of the current manuscript was to replicate published data that show intrathecal infusions of Taxol® (paclitaxel), an anti-neoplastic microtubule stabilizing agent, reduce fibrogliotic scarring caused by a dorsal spinal hemisection (DHx) injury and increase functional recovery and growth of serotonergic axons after moderate spinal contusion injury. These experiments were completed as part of an NIH-NINDS contract entitled "Facilities of Research Excellence in Spinal Cord Injury (FORE-SCI) - Replication". Here, data are presented that confirm the anti-scarring effects of Taxol after DHx injury; however, Taxol did not confer neuroprotection or promote serotonergic axon growth nor did it improve functional recovery in a model of moderate spinal contusion injury. Thus, only partial replication was achieved. Possible explanations for disparate results in our studies and published data are discussed.
摘要
本手稿的目的是复制已发表的数据，这些数据表明鞘内注射抗肿瘤微管稳定剂紫杉醇（Taxol®）可减少脊髓背侧半横断（DHx）损伤引起的纤维性瘢痕形成，并在中度脊髓挫伤损伤后增加5-羟色胺能轴突的功能恢复和生长。这些实验是作为美国国立卫生研究院（NIH）-国立神经疾病和中风研究所（NINDS）名为“脊髓损伤卓越研究设施（FORE-SCI）-复制”合同的一部分完成的。在此，我们展示的数据证实了紫杉醇在DHx损伤后的抗瘢痕作用；然而，在中度脊髓挫伤损伤模型中，紫杉醇并未提供神经保护作用，也未促进5-羟色胺能轴突生长，也未改善功能恢复。因此，仅实现了部分复制。我们讨论了我们的研究结果与已发表数据存在差异的可能原因。
相似文献
1
Independent evaluation of the anatomical and behavioral effects of Taxol in rat models of spinal cord injury.对紫杉醇在大鼠脊髓损伤模型中的解剖学和行为学效应进行独立评估。
Exp Neurol. 2014 Nov;261:97-108. doi: 10.1016/j.expneurol.2014.06.020. Epub 2014 Jul 3.
2
Neutralization of inhibitory molecule NG2 improves synaptic transmission, retrograde transport, and locomotor function after spinal cord injury in adult rats.抑制分子 NG2 的中和作用可改善成年大鼠脊髓损伤后的突触传递、逆行运输和运动功能。
J Neurosci. 2013 Feb 27;33(9):4032-43. doi: 10.1523/JNEUROSCI.4702-12.2013.
3
A re-assessment of the effects of treatment with a non-steroidal anti-inflammatory (ibuprofen) on promoting axon regeneration via RhoA inhibition after spinal cord injury.重新评估非甾体类抗炎药（布洛芬）通过抑制 RhoA 促进脊髓损伤后轴突再生的治疗效果。
Exp Neurol. 2013 Oct;248:321-37. doi: 10.1016/j.expneurol.2013.06.023. Epub 2013 Jul 2.
4
Systemic epothilone D improves hindlimb function after spinal cord contusion injury in rats.系统性埃坡霉素 D 可改善大鼠脊髓挫伤后后肢功能。
Exp Neurol. 2018 Aug;306:250-259. doi: 10.1016/j.expneurol.2018.01.018. Epub 2018 Feb 2.
5
A combination of taxol infusion and human umbilical cord mesenchymal stem cells transplantation for the treatment of rat spinal cord injury.紫杉醇输注联合人脐带间充质干细胞移植治疗大鼠脊髓损伤。
Brain Res. 2012 Oct 24;1481:79-89. doi: 10.1016/j.brainres.2012.08.051. Epub 2012 Aug 31.
6
Suppression of fibrous scarring in spinal cord injury of rat promotes long-distance regeneration of corticospinal tract axons, rescue of primary motoneurons in somatosensory cortex and significant functional recovery.抑制大鼠脊髓损伤中的纤维瘢痕形成可促进皮质脊髓束轴突的长距离再生、挽救体感皮层中的初级运动神经元并实现显著的功能恢复。
Eur J Neurosci. 2005 Dec;22(12):3047-58. doi: 10.1111/j.1460-9568.2005.04495.x.
7
Axonal regeneration. Systemic administration of epothilone B promotes axon regeneration after spinal cord injury.轴突再生。埃坡霉素B的全身给药可促进脊髓损伤后的轴突再生。
Science. 2015 Apr 17;348(6232):347-52. doi: 10.1126/science.aaa2958. Epub 2015 Mar 12.
8
A re-assessment of the effects of a Nogo-66 receptor antagonist on regenerative growth of axons and locomotor recovery after spinal cord injury in mice.对Nogo-66受体拮抗剂对小鼠脊髓损伤后轴突再生生长和运动功能恢复影响的重新评估。
Exp Neurol. 2008 Feb;209(2):446-68. doi: 10.1016/j.expneurol.2007.12.010. Epub 2007 Dec 23.
9
Behavioral and anatomical consequences of repetitive mild thoracic spinal cord contusion injury in the rat.重复轻度胸段脊髓挫伤对大鼠行为和解剖结构的影响。
Exp Neurol. 2014 Jul;257:57-69. doi: 10.1016/j.expneurol.2014.04.016. Epub 2014 Apr 28.
10
Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury.微管稳定化减少脊髓损伤后的瘢痕形成并促进轴突再生。
Science. 2011 Feb 18;331(6019):928-31. doi: 10.1126/science.1201148. Epub 2011 Jan 27.
引用本文的文献
1
Paclitaxel alleviates spinal cord injury via activation of the Wnt/β-catenin signaling pathway.紫杉醇通过激活Wnt/β-连环蛋白信号通路减轻脊髓损伤。
Mol Med. 2025 May 6;31(1):172. doi: 10.1186/s10020-025-01240-3.
2
Spinal cord injury-induced metabolic impairment and steatohepatitis develops in non-obese rats and is exacerbated by premorbid obesity.脊髓损伤引起的代谢损伤和肝脂肪变性在非肥胖大鼠中发展，并因预发性肥胖而加重。
Exp Neurol. 2024 Sep;379:114847. doi: 10.1016/j.expneurol.2024.114847. Epub 2024 Jun 8.
3
Mechanisms of Axon Growth and Regeneration: Moving between Development and Disease.轴突生长和再生的机制：在发育和疾病之间游走。
J Neurosci. 2022 Nov 9;42(45):8393-8405. doi: 10.1523/JNEUROSCI.1131-22.2022.
4
Paclitaxel-incorporated nanoparticles improve functional recovery after spinal cord injury.负载紫杉醇的纳米颗粒可改善脊髓损伤后的功能恢复。
Front Pharmacol. 2022 Aug 5;13:957433. doi: 10.3389/fphar.2022.957433. eCollection 2022.
5
Microtubule Organization Is Essential for Maintaining Cellular Morphology and Function.微管组织对于维持细胞形态和功能至关重要。
Oxid Med Cell Longev. 2022 Mar 7;2022:1623181. doi: 10.1155/2022/1623181. eCollection 2022.
6
Fibrosis in the central nervous system: from the meninges to the vasculature.中枢神经系统中的纤维化：从脑膜到脉管系统。
Cell Tissue Res. 2022 Mar;387(3):351-360. doi: 10.1007/s00441-021-03491-y. Epub 2021 Jun 30.
7
Liver inflammation at the time of spinal cord injury enhances intraspinal pathology, liver injury, metabolic syndrome and locomotor deficits.脊髓损伤时的肝脏炎症会加重脊髓内病理学改变、肝脏损伤、代谢综合征和运动功能障碍。
Exp Neurol. 2021 Aug;342:113725. doi: 10.1016/j.expneurol.2021.113725. Epub 2021 Apr 30.
8
Hydrogels as delivery systems for spinal cord injury regeneration.水凝胶作为脊髓损伤再生的递送系统。
Mater Today Bio. 2021 Jan 22;9:100093. doi: 10.1016/j.mtbio.2021.100093. eCollection 2021 Jan.
9
Loss of PIGK function causes severe infantile encephalopathy and extensive neuronal apoptosis.PIGK 功能缺失导致严重的婴儿型脑病和广泛的神经元凋亡。
Hum Genet. 2021 May;140(5):791-803. doi: 10.1007/s00439-020-02243-2. Epub 2021 Jan 4.
10
Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury.慢性神经元激活增加动态微管，以增强背根挤压损伤后的功能性轴突再生。
Nat Commun. 2020 Nov 30;11(1):6131. doi: 10.1038/s41467-020-19914-3.
本文引用的文献
1
Minimum information about a spinal cord injury experiment: a proposed reporting standard for spinal cord injury experiments.脊髓损伤实验的最低信息：脊髓损伤实验报告标准建议
J Neurotrauma. 2014 Aug 1;31(15):1354-61. doi: 10.1089/neu.2014.3400. Epub 2014 Jul 11.
2
Paclitaxel: new uses for an old drug.紫杉醇：旧药新用途。
Drug Des Devel Ther. 2014 Feb 20;8:279-84. doi: 10.2147/DDDT.S56801. eCollection 2014.
3
Functional regeneration beyond the glial scar.超越神经胶质瘢痕的功能再生。
Exp Neurol. 2014 Mar;253:197-207. doi: 10.1016/j.expneurol.2013.12.024. Epub 2014 Jan 11.
4
Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury.血管周细胞在创伤性脊髓损伤后形成纤维疤痕。
J Neurosci. 2013 Aug 21;33(34):13882-7. doi: 10.1523/JNEUROSCI.2524-13.2013.
5
A reassessment of a classic neuroprotective combination therapy for spinal cord injured rats: LPS/pregnenolone/indomethacin.经典神经保护联合疗法治疗脊髓损伤大鼠的再评价：LPS/孕烯醇酮/吲哚美辛。
Exp Neurol. 2012 Feb;233(2):677-85. doi: 10.1016/j.expneurol.2011.11.045. Epub 2011 Dec 8.
6
Recovery from chronic spinal cord contusion after Nogo receptor intervention.Nogo 受体干预后慢性脊髓挫伤的恢复。
Ann Neurol. 2011 Nov;70(5):805-21. doi: 10.1002/ana.22527.
7
Taxol facilitates axon regeneration in the mature CNS.紫杉醇促进成熟中枢神经系统中的轴突再生。
J Neurosci. 2011 Feb 16;31(7):2688-99. doi: 10.1523/JNEUROSCI.4885-10.2011.
8
Microtubule stabilization reduces scarring and causes axon regeneration after spinal cord injury.微管稳定化减少脊髓损伤后的瘢痕形成并促进轴突再生。
Science. 2011 Feb 18;331(6019):928-31. doi: 10.1126/science.1201148. Epub 2011 Jan 27.
9
Independent evaluation of the effects of glibenclamide on reducing progressive hemorrhagic necrosis after cervical spinal cord injury.对格列本脲减少颈髓损伤后进行性出血性坏死的效果进行独立评估。
Exp Neurol. 2012 Feb;233(2):615-22. doi: 10.1016/j.expneurol.2010.11.016. Epub 2010 Dec 9.
10
Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research.改进生物科学研究报告：动物研究报告的ARRIVE指南
PLoS Biol. 2010 Jun 29;8(6):e1000412. doi: 10.1371/journal.pbio.1000412.
Zotero 插件