Implantation of Brain-Derived Extracellular Matrix Enhances Neurological Recovery after Traumatic Brain Injury.

Implantation of Brain-Derived Extracellular Matrix Enhances Neurological Recovery after Traumatic Brain Injury.
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DOI:
10.1177/0963689717714090
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发表时间:
2017-07
影响因子:
3.3
通讯作者:
Chen L
Chen L
中科院分区:
医学4区
文献类型:
--
作者:
Wu Y;Wang J;Shi Y;Pu H;Leak RK;Liou AKF;Badylak SF;Liu Z;Zhang J;Chen J;Chen L

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由细胞外基质(ECM)组成的支架在促进脑组织重塑和损伤后修复方面的能力正在被研究。本研究验证了植入脑源性细胞外基质可以减轻实验性创伤性脑损伤的假设,并探索了潜在的潜在机制。用控制性皮质撞击(CCI)诱导小鼠脑损伤。用去细胞方法从正常猪脑组织中分离出细胞外基质,制成水凝胶,在CCI后1h注射到患侧胼胝体和纹状体内。在伤后35d对损伤灶体积和神经功能进行评估。用免疫组织化学方法评价脑损伤后脑白质的完整性、反应性星形胶质细胞增生和小胶质细胞的激活。我们发现,ECM治疗减少了病变体积,改善了神经行为功能。与对照组、赋形剂治疗的小鼠相比,ECM治疗的小鼠显示出较少的脑损伤后海马区神经退行性变和白质损伤。此外,ECM还可改善脑损伤后的胶质增生和小胶质细胞的促炎反应,从而为组织修复提供良好的微环境。我们的研究表明,脑ECM水凝胶植入改善了脑微环境,促进了脑创伤后组织的恢复。脑ECM具有良好的生物相容性,可单独或与其他治疗方法联合使用,具有作为脑外伤治疗剂的潜力。
Scaffolds composed of extracellular matrix (ECM) are being investigated for their ability to facilitate brain tissue remodeling and repair following injury. The present study tested the hypothesis that the implantation of brain-derived ECM would attenuate experimental traumatic brain injury (TBI) and explored potential underlying mechanisms. TBI was induced in mice by a controlled cortical impact (CCI). ECM was isolated from normal porcine brain tissue by decellularization methods, prepared as a hydrogel, and injected into the ipsilesional corpus callosum and striatum 1 h after CCI. Lesion volume and neurological function were evaluated up to 35 d after TBI. Immunohistochemistry was performed to assess post-TBI white matter integrity, reactive astrogliosis, and microglial activation. We found that ECM treatment reduced lesion volume and improved neurobehavioral function. ECM-treated mice showed less post-TBI neurodegeneration in the hippocampus and less white matter injury than control, vehicle-treated mice. Furthermore, ECM ameliorated TBI-induced gliosis and microglial pro-inflammatory responses, thereby providing a favorable microenvironment for tissue repair. Our study indicates that brain ECM hydrogel implantation improved the brain microenvironment that facilitates post-TBI tissue recovery. Brain ECM offers excellent biocompatibility and holds potential as a therapeutic agent for TBI, alone or in combination with other treatments.
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