Neuroprotective effect of subdural infusion of serp-1 in spinal cord trauma

Jacek M. Kwiecien, Wojciech Dabrowski, Bryce J. Kwiecien-Delaney, Christian J. Kwiecien-Delaney, Dorota Siwicka-Gieroba, Jordan R. Yaron, Liqiang Zhang, Kathleen H. Delaney, Alexandra R. Lucas

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number372
JournalBiomedicines
Volume8
Issue number10
DOIs
StatePublished - Oct 2020

Keywords

  • Cavity of injury
  • Histology
  • Macrophage
  • Neuroprotective therapy
  • Serp-1
  • Spinal cord injury

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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