NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury
NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury
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NT3-壳聚糖引发强大的内源性神经发生，使脊髓损伤后功能恢复
DOI：
10.1073/pnas.1510194112
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发表时间：
2015-10-27
影响因子：
11.1
通讯作者：
Li, Xiaoguang
中科院分区：
文献类型：
--
作者：
Yang, Zhaoyang;Zhang, Aifeng;Li, Xiaoguang
脊髓损伤（Spinal Cord Injury，SCI）是一种目前无法治愈的疾病。在这项研究中，我们发现一种可生物降解的材料，壳聚糖，当加载神经营养因子-3（NT 3）时，允许缓慢释放这种神经营养因子，为再生提供最佳的微环境。NT-3-壳聚糖，当插入完全横断和切除的大鼠胸脊髓的5 mm间隙时，引起内源性神经干细胞的强烈激活，形成功能性神经网络，其互连切断的上行和下行轴突，导致感觉和运动行为恢复。我们的研究表明，通过NT 3-壳聚糖促进内源性神经发生可能是治疗SCI的新策略。成年哺乳动物中枢神经系统（CNS）中的神经干细胞（Neural Stem Cells，NSCs）通过适当的激活、分化和成熟，建立新生神经网络，并整合到受损的神经回路中修复功能，是神经再生的关键。然而，CNS损伤微环境通常是抑制性和炎症性的，限制了活化的NSC分化成神经元和形成新生回路的能力。在这里，我们报告说，神经营养因子-3（NT 3）耦合壳聚糖生物材料，当插入到一个5毫米的间隙完全横断和切除大鼠胸脊髓，引起强大的激活内源性神经干细胞在损伤的脊髓。通过缓慢释放NT 3，生物材料吸引NSCs迁移到病变区域，分化为神经元，并形成功能性神经网络，将切断的上行和下行轴突连接起来，导致感觉和运动行为恢复。我们的研究表明，增强内源性神经发生可能是治疗脊髓损伤的一种新策略。
Significance Spinal cord injury (SCI) is a debilitating medical condition with no cure at present time. In this study we have discovered that a biodegradable material, chitosan, when loaded with, Neurotrophin-3 (NT3), allowed for slow release of this neural trophic factor, providing an optimal microenvironment for regeneration. NT3-chitosan, when inserted into a 5 mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous neural stem cells forming functional neural networks, which interconnected the severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis by NT3-chitosan could be a novel strategy for treatment of SCI. Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.