Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model

Jacek M. Kwiecien; Wojciech Dabrowski; Barbara Marzec-Kotarska; Christian J. Kwiecien-Delaney; Jordan R. Yaron; Liqiang Zhang; Lauren Schutz; Alexandra R. Lucas

doi:10.5114/fn.2019.83830

eISSN: 1509-572x
ISSN: 1641-4640

Folia Neuropathologica

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1/2019
vol. 57

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abstract:

Original paper

Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model

Jacek M. Kwiecien

,

Wojciech Dabrowski

,

Barbara Marzec-Kotarska

,

Christian J. Kwiecien-Delaney

,

Jordan R. Yaron

,

Liqiang Zhang

,

Lauren Schutz

,

Alexandra R. Lucas

Folia Neuropathol 2019; 57 (1): 41-50

DOI: https://doi.org/10.5114/fn.2019.83830

Online publish date: 2019/03/29

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AMA

Kwiecien J, Dabrowski W, Marzec-Kotarska B, et al. Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model. Folia Neuropathologica. 2019;57(1):41-50. doi:10.5114/fn.2019.83830.

APA

Kwiecien, J., Dabrowski, W., Marzec-Kotarska, B., Kwiecien-Delaney, C., Yaron, J.,  & Zhang, L. et al. (2019). Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model. Folia Neuropathologica, 57(1), 41-50. https://doi.org/10.5114/fn.2019.83830

Chicago

Kwiecien, Jacek M., Wojciech Dabrowski, Barbara Marzec-Kotarska, Christian J. Kwiecien-Delaney, Jordan R. Yaron, Liqiang Zhang,  and Lauren Schutz et al. 2019. "Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model". Folia Neuropathologica 57 (1): 41-50. doi:10.5114/fn.2019.83830.

Harvard

Kwiecien, J., Dabrowski, W., Marzec-Kotarska, B., Kwiecien-Delaney, C., Yaron, J., Zhang, L., Schutz, L.,  and Lucas, A. (2019). Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model. Folia Neuropathologica, 57(1), pp.41-50. https://doi.org/10.5114/fn.2019.83830

MLA

Kwiecien, Jacek M. et al. "Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model." Folia Neuropathologica, vol. 57, no. 1, 2019, pp. 41-50. doi:10.5114/fn.2019.83830.

Vancouver

Kwiecien J, Dabrowski W, Marzec-Kotarska B, Kwiecien-Delaney C, Yaron J, Zhang L et al. Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model. Folia Neuropathologica. 2019;57(1):41-50. doi:10.5114/fn.2019.83830.

PlumX metrics:

Spinal cord injury (SCI)-initiated inflammation was treated with anti-inflammatory reagents. We compared local spinal cord or intraperitoneal infusion of two Myxoma virus derived immune modulating proteins, Serp-1 and M-T7, with dexamethasone (DEX).

Hemorrhage and necrosis after SCI initiate a complex pathogenesis dominated by early, severe and highly destructive inflammatory macrophage infiltration. We examined sustained, 7-day, subdural infusion of either M-T7, a chemokine modulator or Serp-1, a plasminogen activator and factor inhibitor. Mature male rats had epidural balloon crush SCI and sustained subdural infusion of Serp-1, M-T7, DEX or saline for 7 days via the osmotic pump. A separate group of rats with SCI had intra-peritoneal infusion. Clinical evaluation included endpoint monitoring with body weight, hemorrhagic cystitis and bilateral toe pinch response. Sections of the spinal cord were analyzed histologically and macrophage numbers counted by standardized protocol in the cavity of injury (COI).

While the rats administered DEX demonstrated substantial body weight loss, dehydration and dermal atrophy consistent with steroid toxicity, rats infused with Serp-1 and M-T7 had no toxicity. Serp-1 improved withdrawal responses. Subdural infusion of Serp-1, M-T7 and DEX significantly reduced numbers of phagocytic, CD68-positive macrophages. With intraperitoneal infusion only M-T7 reduced macrophage counts, Serp-1 showed only a trend. Local infusion of highly active immune modulating proteins; Serp-1 and M-T7, targeting serine protease and chemokine pathways demonstrated excellent potential for neuroprotection after severe SCI in a rat model, without adverse side effects. Sustained subdural infusion offers an alternative route of administration for treatment of SCI.

keywords:

Myxoma virus derived immune modulating proteins, M-T7 and Serp-1, reduce early inflammation after spinal cord injury in the rat model

Jacek M. Kwiecien , Wojciech Dabrowski , Barbara Marzec-Kotarska , Christian J. Kwiecien-Delaney , Jordan R. Yaron , Liqiang Zhang , Lauren Schutz , Alexandra R. Lucas

spinal cord injury, neuroinflammation, subdural infusion, neuroprotection

Jacek M. Kwiecien

,

Wojciech Dabrowski

,

Barbara Marzec-Kotarska

,

Christian J. Kwiecien-Delaney

,

Jordan R. Yaron

,

Liqiang Zhang

,

Lauren Schutz

,

Alexandra R. Lucas