Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate‐Induced Excitotoxicity,Advanced Materials

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Biodegradable Spheres Protect Traumatically Injured Spinal Cord by Alleviating the Glutamate‐Induced Excitotoxicity
Advanced Materials ( IF 27.4 ) Pub Date : 2018-02-14 , DOI: 10.1002/adma.201706032
Dongfei Liu _{1,

2,

3} , Jian Chen ₄ , Tao Jiang _{4,

5} , Wei Li ₁ , Yao Huang _{4,

6} , Xiyi Lu ₇ , Zehua Liu ₁ , Weixia Zhang ₃ , Zheng Zhou ₄ , Qirui Ding ₄ , Hélder A. Santos _{1,

2} , Guoyong Yin ₄ , Jin Fan ₄

Affiliation

New treatment strategies for spinal cord injury with good therapeutic efficacy are actively pursued. Here, acetalated dextran (AcDX), a biodegradable polymer obtained by modifying vicinal diols of dextran, is demonstrated to protect the traumatically injured spinal cord. To facilitate its administration, AcDX is formulated into microspheres (≈7.2 µm in diameter) by the droplet microfluidic technique. Intrathecally injected AcDX microspheres effectively reduce the traumatic lesion volume and inflammatory response in the injured spinal cord, protect the spinal cord neurons from apoptosis, and ultimately, recover the locomotor function of injured rats. The neuroprotective feature of AcDX microspheres is achieved by sequestering glutamate and calcium ions in cerebrospinal fluid. The scavenging of glutamate and calcium ion reduces the influx of calcium ions into neurons and inhibits the formation of reactive oxygen species. Consequently, AcDX microspheres attenuate the expression of proapoptotic proteins, Calpain, and Bax, and enhance the expression of antiapoptotic protein Bcl‐2. Overall, AcDX microspheres protect traumatically injured spinal cord by alleviating the glutamate‐induced excitotoxicity. This study opens an exciting perspective toward the application of neuroprotective AcDX for the treatment of severe neurological diseases.

中文翻译：

可生物降解球体通过减轻谷氨酸诱导的兴奋性毒性来保护创伤性脊髓损伤

积极寻求具有良好疗效的脊髓损伤的新治疗策略。在此，通过修饰葡聚糖的邻二醇得到的可生物降解的聚合物-缩醛右旋糖酐（AcDX）被证明可以保护受创伤的脊髓。为了促进给药，通过液滴微流技术将AcDX配制成微球（直径约7.2 µm）。鞘内注射AcDX微球可有效减少受伤脊髓的损伤体积和炎症反应，保护脊髓神经元免于细胞凋亡，并最终恢复受伤大鼠的运动功能。通过隔离脑脊液中的谷氨酸和钙离子，可以实现AcDX微球的神经保护功能。清除谷氨酸和钙离子可减少钙离子向神经元的流入并抑制活性氧的形成。因此，AcDX微球会减弱促凋亡蛋白，钙蛋白酶和Bax的表达，并增强抗凋亡蛋白Bcl-2的表达。总体而言，AcDX微球通过减轻谷氨酸引起的兴奋性毒性来保护受创伤的脊髓。这项研究为神经保护性AcDX在严重神经系统疾病治疗中的应用开辟了令人兴奋的前景。AcDX微球通过减轻谷氨酸引起的兴奋性毒性来保护受创伤的脊髓。这项研究为神经保护性AcDX在严重神经系统疾病治疗中的应用开辟了令人兴奋的前景。AcDX微球通过减轻谷氨酸引起的兴奋性毒性来保护受创伤的脊髓。这项研究为神经保护性AcDX在严重神经系统疾病治疗中的应用开辟了令人兴奋的前景。

更新日期：2018-02-14

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