Cargando…

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

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 conv...

Descripción completa

Detalles Bibliográficos
Autores principales: Kwiecien, Jacek M., Dabrowski, Wojciech, Kwiecien-Delaney, Bryce J., Kwiecien-Delaney, Christian J., Siwicka-Gieroba, Dorota, Yaron, Jordan R., Zhang, Liqiang, Delaney, Kathleen H., Lucas, Alexandra R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598159/
https://www.ncbi.nlm.nih.gov/pubmed/32977430
http://dx.doi.org/10.3390/biomedicines8100372
_version_ 1783602524468543488
author Kwiecien, Jacek M.
Dabrowski, Wojciech
Kwiecien-Delaney, Bryce J.
Kwiecien-Delaney, Christian J.
Siwicka-Gieroba, Dorota
Yaron, Jordan R.
Zhang, Liqiang
Delaney, Kathleen H.
Lucas, Alexandra R.
author_facet Kwiecien, Jacek M.
Dabrowski, Wojciech
Kwiecien-Delaney, Bryce J.
Kwiecien-Delaney, Christian J.
Siwicka-Gieroba, Dorota
Yaron, Jordan R.
Zhang, Liqiang
Delaney, Kathleen H.
Lucas, Alexandra R.
author_sort Kwiecien, Jacek M.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7598159
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75981592020-10-31 Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma Kwiecien, Jacek M. Dabrowski, Wojciech Kwiecien-Delaney, Bryce J. Kwiecien-Delaney, Christian J. Siwicka-Gieroba, Dorota Yaron, Jordan R. Zhang, Liqiang Delaney, Kathleen H. Lucas, Alexandra R. Biomedicines Communication 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. MDPI 2020-09-23 /pmc/articles/PMC7598159/ /pubmed/32977430 http://dx.doi.org/10.3390/biomedicines8100372 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Kwiecien, Jacek M.
Dabrowski, Wojciech
Kwiecien-Delaney, Bryce J.
Kwiecien-Delaney, Christian J.
Siwicka-Gieroba, Dorota
Yaron, Jordan R.
Zhang, Liqiang
Delaney, Kathleen H.
Lucas, Alexandra R.
Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma
title Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma
title_full Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma
title_fullStr Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma
title_full_unstemmed Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma
title_short Neuroprotective Effect of Subdural Infusion of Serp-1 in Spinal Cord Trauma
title_sort neuroprotective effect of subdural infusion of serp-1 in spinal cord trauma
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598159/
https://www.ncbi.nlm.nih.gov/pubmed/32977430
http://dx.doi.org/10.3390/biomedicines8100372
work_keys_str_mv AT kwiecienjacekm neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma
AT dabrowskiwojciech neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma
AT kwieciendelaneybrycej neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma
AT kwieciendelaneychristianj neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma
AT siwickagierobadorota neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma
AT yaronjordanr neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma
AT zhangliqiang neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma
AT delaneykathleenh neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma
AT lucasalexandrar neuroprotectiveeffectofsubduralinfusionofserp1inspinalcordtrauma