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

• Published in: Biomedicines Vol. 8; no. 10; p. 372
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 23.09.2020; MDPI
• Subjects: Bladder; Catheters; cavity of injury; CD163 antigen; Communication; Hemorrhage; histology; Immunomodulation; Inflammation; macrophage; Macrophages; Myxoma; Necrosis; Neuroprotection; neuroprotective therapy; Phagocytes; Proteins; Serp-1; Spinal cord; Spinal cord injuries; spinal cord injury; Transplants & implants; Trauma; Canada; United States > US
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines8100372

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.