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Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma

1
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8S 4K1, Canada
2
Department of Anaesthesiology and Intensive Therapy, Medical University of Lublin, 20-090 Lublin, Poland
3
Faculty of Science, McMaster University, Hamilton, ON L8S 4K1, Canada
4
Center for Personalized Diagnostics and Center for Immunotherapy, Vaccines and Virotherapy, Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(10), 372; https://doi.org/10.3390/biomedicines8100372
Received: 22 July 2020 / Revised: 9 September 2020 / Accepted: 21 September 2020 / Published: 23 September 2020
(This article belongs to the Special Issue Advancements in the Treatment of Spinal Cord Injury)
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. View Full-Text
Keywords: spinal cord injury; macrophage; neuroprotective therapy; Serp-1; cavity of injury; histology spinal cord injury; macrophage; neuroprotective therapy; Serp-1; cavity of injury; histology
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MDPI and ACS Style

Kwiecien, J.M.; Dabrowski, W.; Kwiecien-Delaney, B.J.; Kwiecien-Delaney, C.J.; Siwicka-Gieroba, D.; Yaron, J.R.; Zhang, L.; Delaney, K.H.; Lucas, A.R. Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma. Biomedicines 2020, 8, 372. https://doi.org/10.3390/biomedicines8100372

AMA Style

Kwiecien JM, Dabrowski W, Kwiecien-Delaney BJ, Kwiecien-Delaney CJ, Siwicka-Gieroba D, Yaron JR, Zhang L, Delaney KH, Lucas AR. Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma. Biomedicines. 2020; 8(10):372. https://doi.org/10.3390/biomedicines8100372

Chicago/Turabian Style

Kwiecien, Jacek M., Wojciech Dabrowski, Bryce J. Kwiecien-Delaney, Christian J. Kwiecien-Delaney, Dorota Siwicka-Gieroba, Jordan R. Yaron, Liqiang Zhang, Kathleen H. Delaney, and Alexandra R. Lucas 2020. "Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma" Biomedicines 8, no. 10: 372. https://doi.org/10.3390/biomedicines8100372

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