TY - JOUR
T1 - Neuroprotective effect of subdural infusion of serp-1 in spinal cord trauma
AU - Kwiecien, Jacek M.
AU - Dabrowski, Wojciech
AU - Kwiecien-Delaney, Bryce J.
AU - Kwiecien-Delaney, Christian J.
AU - Siwicka-Gieroba, Dorota
AU - Yaron, Jordan R.
AU - Zhang, Liqiang
AU - Delaney, Kathleen H.
AU - Lucas, Alexandra R.
N1 - Funding Information:
This research was funded in part by VPC NeuroPath CONSULTING, Inc., Canada and by Medical University of Lublin, Poland. We wish to acknowledge expert histologic and immunohistochemical service provided by Mary Jo Smith and Mary Bruni, MIRC Histology Laboratory, McMaster University
Funding Information:
Funding: This research was funded in part by VPC NeuroPath CONSULTING, Inc., Canada and by Medical University of Lublin, Poland.
Publisher Copyright:
© 2020 by the authors.
PY - 2020/10
Y1 - 2020/10
N2 - 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.
AB - 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.
KW - Cavity of injury
KW - Histology
KW - Macrophage
KW - Neuroprotective therapy
KW - Serp-1
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=85092512795&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85092512795&partnerID=8YFLogxK
U2 - 10.3390/BIOMEDICINES8100372
DO - 10.3390/BIOMEDICINES8100372
M3 - Article
AN - SCOPUS:85092512795
SN - 2227-9059
VL - 8
JO - Biomedicines
JF - Biomedicines
IS - 10
M1 - 372
ER -