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采用等离子体合成聚吡咯/碘联合混合康复方案治疗外伤性脊髓损伤后的运动功能恢复。

Recovery of motor function after traumatic spinal cord injury by using plasma-synthesized polypyrrole/iodine application in combination with a mixed rehabilitation scheme.

机构信息

Instituto Mexicano del Seguro Social, Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI. Av. Cuauhtémoc 330, Col. Doctores, México City, CP, 06720, México.

Doctorate in Biological and Health Sciences, Universidad Autónoma Metropolitana, Iztapalapa, Mexico City, CP, 09340, Mexico.

出版信息

J Mater Sci Mater Med. 2020 Jun 30;31(7):58. doi: 10.1007/s10856-020-06395-5.

Abstract

Traumatic spinal cord injury (TSCI) can cause paralysis and permanent disability. Rehabilitation (RB) is currently the only accepted treatment, although its beneficial effect is limited. The development of biomaterials has provided therapeutic possibilities for TSCI, where our research group previously showed that the plasma-synthesized polypyrrole/iodine (PPy/I), a biopolymer with different physicochemical characteristics than those of the PPy synthesized by conventional methods, promotes recovery of motor function after TSCI. The present study evaluated if the plasma-synthesized PPy/I applied in combination with RB could increase its beneficial effects and the mechanisms involved. Adult rats with TSCI were divided into no treatment (control); biopolymer (PPy/I); mixed RB by swimming and enriched environment (SW/EE); and combined treatment (PPy/I + SW/EE) groups. Eight weeks after TSCI, the general health of the animals that received any of the treatments was better than the control animals. Functional recovery evaluated by two scales was better and was achieved in less time with the PPy/I + SW/EE combination. All treatments significantly increased βIII-tubulin (nerve plasticity) expression, but only PPy/I increased GAP-43 (nerve regeneration) and MBP (myelination) expression when were analyzed by immunohistochemistry. The expression of GFAP (glial scar) decreased in treated groups when determined by histochemistry, while morphometric analysis showed that tissue was better preserved when PPy/I and PPy/I + SW/EE were administered. The application of PPy/I + SW/EE, promotes the preservation of nervous tissue, and the expression of molecules related to plasticity as βIII-tubulin, reduces the glial scar, improves general health and allows the recovery of motor function after TSCI. The implant of the biomaterial polypyrrole/iodine (PPy/I) synthesized by plasma (an unconventional synthesis method), in combination with a mixed rehabilitation scheme with swimming and enriched environment applied after a traumatic spinal cord injury, promotes expression of GAP-43 and βIII-tubulin (molecules related to plasticity and nerve regeneration) and reduces the expression of GFAP (molecule related to the formation of the glial scar). Both effects together allow the formation of nerve fibers, the reconnection of the spinal cord in the area of injury and the recovery of lost motor function. The figure shows the colocalization (yellow) of βIII-tubilin (red) and GAP-43 (green) in fibers crossing the epicenter of the injury (arrowheads) that reconnect the rostral and caudal ends of the injured spinal cord and allowed recovery of motor function.

摘要

创伤性脊髓损伤(TSCI)可导致瘫痪和永久性残疾。康复(RB)是目前唯一被接受的治疗方法,尽管其有益效果是有限的。生物材料的发展为 TSCI 提供了治疗的可能性,我们的研究小组此前曾表明,等离子体合成的聚吡咯/碘(PPy/I),一种具有不同于常规方法合成的 PPy 的物理化学特性的生物聚合物,可促进 TSCI 后的运动功能恢复。本研究评估了等离子体合成的 PPy/I 与 RB 联合应用是否可以增加其有益效果和涉及的机制。成年 TSCI 大鼠分为未治疗(对照);生物聚合物(PPy/I);混合游泳和丰富环境的 RB(SW/EE);和联合治疗(PPy/I+SW/EE)组。TSCI 后 8 周,接受任何治疗的动物的整体健康状况均优于对照动物。通过两种量表评估的功能恢复更好,并且用 PPy/I+SW/EE 联合治疗在更短的时间内实现。所有治疗均显著增加了βIII-微管蛋白(神经可塑性)的表达,但只有 PPy/I 增加了 GAP-43(神经再生)和 MBP(髓鞘化)的表达,当通过免疫组织化学分析时。组织化学测定时,GFAP(神经胶质瘢痕)的表达减少,而形态计量分析表明,当给予 PPy/I 和 PPy/I+SW/EE 时,组织保存更好。PPy/I+SW/EE 的应用促进了神经组织的保存,以及与可塑性相关的分子的表达,如βIII-微管蛋白,减少了神经胶质瘢痕,改善了整体健康状况,并允许在 TSCI 后恢复运动功能。等离子体(一种非常规的合成方法)合成的生物材料聚吡咯/碘(PPy/I)的植入物与创伤性脊髓损伤后应用的游泳和丰富环境混合康复方案相结合,可促进 GAP-43 和βIII-微管蛋白(与可塑性和神经再生相关的分子)的表达,并减少 GFAP(与神经胶质瘢痕形成相关的分子)的表达。这两种作用共同允许神经纤维的形成,损伤区脊髓的重新连接以及丧失的运动功能的恢复。该图显示了 βIII-微管蛋白(红色)和 GAP-43(绿色)在穿过损伤中心的纤维(箭头)中的共定位(黄色),这些纤维重新连接了损伤脊髓的头端和尾端,并恢复了运动功能。

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