Local application of MDL28170-loaded PCL film improves functional recovery by preserving survival of motor neurons after traumatic spinal cord injury
| Autor: | Weijian Tang, Teng He, Ying-ying Chen, Chao Wang, Dongling Shi, Mingzhi Zheng, Heyangzi Li, Yue-Liang Shen, Hongfeng Jin, Yuemin Ding, Jue Hu, Xinghui Song, Lin-Lin Wang |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cell Survival Polyesters Biocompatible Materials Rats Sprague-Dawley Lesion 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems GAP-43 Protein 0302 clinical medicine Downregulation and upregulation medicine Animals Gliosis Viability assay Spinal cord injury Cells Cultured Spinal Cord Injuries Glycoproteins Motor Neurons Cell Death biology Chemistry General Neuroscience Endoplasmic reticulum Calpain Dipeptides Recovery of Function Tunicamycin Endoplasmic Reticulum Stress medicine.disease Cell biology 030104 developmental biology medicine.anatomical_structure biology.protein Female Neuron medicine.symptom Locomotion 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience Letters. 694:161-167 |
| ISSN: | 0304-3940 |
| DOI: | 10.1016/j.neulet.2018.12.006 |
| Popis: | Neuronal death and organization degeneration can happen inordinately after spinal cord injury (SCI), which lead to nerve dysfunction. We aimed to determine whether local application of a cell permeable calpain I inhibitor (MDL28170) can promote SCI recovery by increasing neuronal cell viability. MDL28170-loaded polycaprolactone (PCL) film was fabricated. Scanning electron microscopy showed the surface of PCL film was smooth with holes (diameter at μM level). The PCL film was non-toxic, biological compatibility, and had good neuron adhension and slow release characteristic. MDL28170 increased VSC4.1 motor neurons' viability under tunicamycin (an endoplasmic reticulum stress) induced injury. In a traumatic SCI rat model, MDL28170-loaded PCL film reduced the area of lesion cavity, and promoted recovery of locomotor behavior. Moreover, the expression of GAP-43 was upregulated after MDL28170-loaded PCL film treatment. Thus, our findings demonstrated that localized delivery of MDL28170 could promote SCI recovery by inhibiting endoplasmic reticulum stress, preserving survival of the motor neurons, which may point out a promising therapeutic target for treating SCI patient. |
| Databáze: | OpenAIRE |
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