| Autor: |
Kwiecien JM; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada., Dabrowski W; Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, 20-090 Lublin, Poland., Kwiecien-Delaney BJ; Faculty of Science, McMaster University, Hamilton, ON L8S 4K1, Canada., Kwiecien-Delaney CJ; Faculty of Science, McMaster University, Hamilton, ON L8S 4K1, Canada., Siwicka-Gieroba D; Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, 20-090 Lublin, Poland., Yaron JR; Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA., Zhang L; Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA., Delaney KH; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada., Lucas AR; Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA. |
| Abstrakt: |
Spinal cord injury (SCI) initiates a severe, destructive inflammation with pro-inflammatory, CD68+/CD163-, phagocytic macrophages infiltrating the area of necrosis and hemorrhage by day 3 and persisting for the next 16 weeks. Inhibition of macrophage infiltration of the site of necrosis that is converted into a cavity of injury (COI) during the first week post-SCI, should limit inflammatory damage, shorten its duration and result in neuroprotection. By sustained subdural infusion we administered Serp-1, a Myxoma virus-derived immunomodulatory protein previously shown to improve neurologic deficits and inhibit macrophage infiltration in the COI in rats with the balloon crush SCI. Firstly, in a 7 day long study, we determined that the optimal dose for macrophage inhibition was 0.2 mg/week. Then, we demonstrated that a continuous subdural infusion of Serp-1 for 8 weeks resulted in consistently accelerated lowering of pro-inflammatory macrophages in the COI and in their almost complete elimination similar to that previously observed at 16 weeks in untreated SCI rats. The macrophage count in the COI is a quantitative test directly related to the severity of destructive inflammation initiated by the SCI. This test has consistently demonstrated anti-inflammatory effect of Serp-1 interpreted as neuroprotection, the first and necessary step in a therapeutic strategy in neurotrauma. |
