Artikel
Combined treatment of self-assembling peptides and neural precursor cells after experimental cervical spinal cord injury
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Veröffentlicht: | 9. Juni 2017 |
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Gliederung
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Objective: The pathophysiology of spinal cord injury (SCI) involves inflammation and tissue scarring interfering with regeneration and recovery. A combined treatment approach with self-assembling peptides (SAP) and neural precursor cells (NPC) might improve this inhibitory environment and neuronal regeneration.
Methods: Following cervical laminectomy, rats were subjected to SCI. After randomization (NPC, SAP, NPC+SAP, vehicle, sham) SAPs and NPCs were injected into the spinal cord 1 day and 14 days after trauma. All animals received growth factors subdurally and immunosuppressive therapy. Neurological function was assessed on a weekly basis. 4 weeks after SCI rats were sacrificed and cryosections were prepared for immunohistochemical staining.
Results: Animals treated with SAPs showed a larger amount of surviving NPCs (18.088 ± 4.044 vs. 11.493 ± 4.111; n=6; p=0.019) and greater levels of differentiation: neurons (8.7% vs. 5.8%; p=0.015) and oligodendrocytes (11.6% vs. 9.1%; p=0.005). Furthermore, animals treated with SAPs alone or as a combined approach with NPCs had smaller intramedullary cysts (p=0.07) and a larger percentage of preserved tissue. In the combined treatment group astrogliosis (GFAP density) and tissue scarring (CSPG density) were significantly reduced. Though the total number of motor-neurons was diminished, there was no significant difference between the groups. Synapto-connectivity (Synaptophysin-density) was increased both in the NPC and in the combined treatment group. Behavioral assessments showed improvements favoring the animals treated combinatorially 8 weeks after SCI.
Summary: Shaping the inhibitory environment using SAPs reduces astrogliosis and tissue-scarring, supports NPC survival and differentiation, and reduces intramedullar cyst formation leading to an improved neurological outcome.
*This work was funded by a grant of the German research society (DFG Forschungsstipendium), and the Krembil and CIHR foundations.