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氧化石墨烯支架促进胸段横断大鼠中由侵入支架的轴突介导的功能改善。

Graphene oxide scaffolds promote functional improvements mediated by scaffold-invading axons in thoracic transected rats.

作者信息

Zaforas Marta, Benayas Esther, Madroñero-Mariscal Raquel, Domínguez-Bajo Ana, Fernández-López Elena, Hernández-Martín Yasmina, González-Mayorga Ankor, Alonso-Calviño Elena, Hernández Eduardo R, López-Dolado Elisa, Rosa Juliana M, Aguilar Juan, Serrano María C

机构信息

Laboratorio de Neurofisiología Experimental, Hospital Nacional de Parapléjicos, Finca La Peraleda s/n, 45071, Toledo, Spain.

Instituto de Ciencia de Materiales de Madrid (ICMM), Consejo Superior de Investigaciones Científicas (CSIC), Calle Sor Juana Inés de la Cruz 3, 28049, Madrid, Spain.

出版信息

Bioact Mater. 2025 Jan 10;47:32-50. doi: 10.1016/j.bioactmat.2024.12.031. eCollection 2025 May.

Abstract

Millions of patients and their caretakers live and deal with the devastating consequences of spinal cord injury (SCI) worldwide. Despite outstanding advances in the field to both understand and tackle these pathologies, a cure for SCI patients, with their peculiar characteristics, is still a mirage. One of the most promising therapeutic strategies to date for these patients involves the use of epidural electrical stimulation. In this context, electrically active materials such as graphene and its derivates become particularly interesting. Indeed, solid evidence of their capacity to closely interact with neural cells and networks is growing. Encouraged by previous findings in our laboratory on the exploration of 3D porous reduced graphene oxide (rGO) scaffolds in chronic cervical hemisected rats (C6), herein we report their neuro-reparative properties when chronically implanted in complete transected rats (T9-T10), in which no preserved contralateral neural networks can assist in any observed recovery. Electrophysiological recordings from brainstem regions show antidromic activation of a small population of neurons in response to electrical stimulation caudal to the injury. These neurons are located in the Gigantocellular nucleus of reticular formation and vestibular nuclei, both regions directly related to motor functions. Together with histological features at the lesion site, such as more abundant and larger blood vessels and more abundant, longer and more homogeneously distributed axons, our results corroborate that rGO scaffolds create a permissive environment that allows the invasion of functional axonic processes from neurons located in brainstem nuclei with motor function in a rat model of complete thoracic transection. Additionally, behavioral tests evidence that these scaffolds play an important role in whole-body mechanical stabilization (postural control) proved by the absence of scoliosis, a higher trunk stability and a larger cervico-thoraco-lumbar movement range in rGO-implanted rats.

摘要

在全球范围内,数以百万计的患者及其护理人员生活并应对脊髓损伤(SCI)带来的毁灭性后果。尽管该领域在理解和解决这些病症方面取得了显著进展,但对于具有特殊特征的SCI患者而言,治愈仍然是遥不可及的梦想。迄今为止,针对这些患者最有前景的治疗策略之一是使用硬膜外电刺激。在这种背景下,诸如石墨烯及其衍生物等电活性材料变得格外引人关注。事实上,它们与神经细胞和神经网络紧密相互作用能力的确凿证据正在不断增加。受我们实验室先前在慢性颈半横断大鼠(C6)中探索三维多孔还原氧化石墨烯(rGO)支架的研究结果鼓舞,在此我们报告其在完全横断大鼠(T9 - T10)中长期植入后的神经修复特性,在这种大鼠中没有保留的对侧神经网络能够协助任何观察到的恢复。来自脑干区域的电生理记录显示,在损伤部位尾侧进行电刺激时,一小部分神经元出现逆向激活。这些神经元位于网状结构的巨细胞核和前庭核,这两个区域都与运动功能直接相关。连同损伤部位的组织学特征,如更丰富、更大的血管以及更丰富、更长且分布更均匀的轴突一起,我们的结果证实rGO支架创造了一个有利环境,允许来自具有运动功能的脑干核中的神经元的功能性轴突生长侵入大鼠完全胸段横断模型中。此外,行为测试证明这些支架在全身机械稳定(姿势控制)中发挥重要作用,这体现在植入rGO的大鼠中没有脊柱侧弯、更高的躯干稳定性以及更大的颈 - 胸 - 腰运动范围。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b7c/11772149/a107205c382f/ga1.jpg

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