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非功能化软藻酸盐水凝胶促进大鼠半侧脊髓切除模型脊髓损伤后的运动功能恢复。

Non-functionalized soft alginate hydrogel promotes locomotor recovery after spinal cord injury in a rat hemimyelonectomy model.

作者信息

Sitoci-Ficici Kerim Hakan, Matyash Marina, Uckermann Ortrud, Galli Roberta, Leipnitz Elke, Later Robert, Ikonomidou Chrysanthy, Gelinsky Michael, Schackert Gabriele, Kirsch Matthias

机构信息

Neurosurgery, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.

Neuropediatrics, University Hospital Carl Gustav Carus, TU Dresden, Dresden, Germany.

出版信息

Acta Neurochir (Wien). 2018 Mar;160(3):449-457. doi: 10.1007/s00701-017-3389-4. Epub 2017 Dec 11.

Abstract

BACKGROUND

Spinal cord injury (SCI) and the consecutive devastating neurological sequelae have an enormous individual and economic impact. Implantation of functionalized hydrogels is a promising approach, because they can serve as a matrix for the regenerating tissue, carry and release bioactive molecules and various cell types. We already demonstrated that non-functionalized soft alginate hydrogel supported axonal outgrowth and protected neurons against oxidative stress in vitro. Here, we investigated the effects of such soft alginate hydrogels on locomotor recovery in small and large spinal cord lesions.

METHOD

Hemimyelonectomy of 2 mm or 4 mm length was performed in rats and soft alginate hydrogel was implanted. Functional recovery of the hindlimbs was assessed in the open field [Batto Beattie Bresnahan (BBB) score] and using swimming test [Louisville Swim score (LSS)] for 140 days post injury (DPI). Reference histology was performed.

RESULTS

Rats that received an alginate implant into 2 mm spinal cord lesions demonstrated significantly improved locomotor recovery compared to controls detectable already at 10 DPI. At 140 DPI, they reached higher LSS and BBB scores in swimming and open field tests, respectively. However, this beneficial effect of alginate was lacking in animals with larger (4 mm) lesions. Histological examination suggested that fibrous scarring in the spinal cord was reduced after alginate implantation in comparison to controls.

CONCLUSIONS

Implantation of soft alginate hydrogel in small spinal cord lesions improved functional recovery. Possible underlying mechanisms include the mechanical stabilization of the wound, reduction of secondary damage and inhibition of fibrous scarring.

摘要

背景

脊髓损伤(SCI)及其随之而来的严重神经后遗症对个人和经济都有巨大影响。功能化水凝胶的植入是一种很有前景的方法,因为它们可以作为再生组织的基质,携带和释放生物活性分子以及各种细胞类型。我们已经证明,非功能化的软藻酸盐水凝胶在体外可支持轴突生长并保护神经元免受氧化应激。在此,我们研究了这种软藻酸盐水凝胶对大小不同的脊髓损伤后运动功能恢复的影响。

方法

在大鼠中进行2毫米或4毫米长的半侧脊髓切除术,并植入软藻酸盐水凝胶。在损伤后140天(DPI),通过旷场试验[巴托·贝蒂·布雷斯纳汉(BBB)评分]和游泳试验[路易斯维尔游泳评分(LSS)]评估后肢的功能恢复情况。进行参考组织学检查。

结果

与对照组相比,在2毫米脊髓损伤处植入藻酸盐的大鼠在伤后10天就显示出明显改善的运动功能恢复。在伤后140天,它们在游泳和旷场试验中分别达到了更高的LSS和BBB评分。然而,在损伤较大(4毫米)的动物中,藻酸盐的这种有益作用并不存在。组织学检查表明,与对照组相比,藻酸盐植入后脊髓中的纤维瘢痕形成减少。

结论

在小面积脊髓损伤中植入软藻酸盐水凝胶可改善功能恢复。可能的潜在机制包括伤口的机械稳定、继发性损伤的减少以及纤维瘢痕形成的抑制。

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