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Temporal Profile and Severity Correlation of a Panel of Rat Spinal Cord Injury Protein Biomarkers

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Abstract

In the USA, there are approximately 12,000 new cases of spinal cord injury (SCI) each year and some 1.2 million people living with paralysis due to SCI. Seven percent of them are paralyzed due to an accident or injury occurring while serving in the military. Here, we report a systematic study on protein biomarker candidates in a rat SCI model with either moderate or severe injury. Tissue, cerebrospinal fluid (CSF), and serum samples were obtained at 4 h, 24 h, and 7 days post-injury. The candidate biomarkers included axonal injury markers αII-spectrin breakdown products (SBDP150/145/120), neuronal cell body injury marker ubiquitin C-terminal hydrolase-L1 (UCH-L1), astrogliosis/astroglial injury markers S100 calcium-binding protein-β (S100β), glial fibrillary acidic protein (GFAP) and GFAP breakdown products (GBDPs), demyelination marker myelin basic protein (MBP), axonal injury marker phosphorylated neurofilament-H (pNF-H), and neuroinflammation marker interleukin-6 (IL-6). SBDP150/145, UCH-L1, GFAP, and S100β were found as acute biomarkers with significantly elevated levels within 24 h. GBDP44, GBDP38, and pNF-H are acute and subacute biomarkers that were found to have increased at 4 h, 24 h, and 7 days. MBP and SBDP120 were considered subacute biomarkers which were only detectable at 7 days post-injury. These results not only allow us to gain important insight into the patho-mechanisms of SCI but also showcase the possibility of using some of the protein biomarkers to track injury severity and disease progression and resolution. These biomarkers can potentially serve as tools that assist therapy development and clinical trials.

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Abbreviations

SCI:

Spinal cord injury

TBI:

Traumatic brain injury

CSF:

Cerebrospinal fluid

GFAP:

Glial fibrillary acidic protein

SBDP:

αII-Spectrin breakdown product

GBDP:

GFAP breakdown product

MBP:

Myelin basic protein

IL-6:

Interleukin-6

pNF-H:

Phosphorylated neurofilament-H

S100β:

S100 calcium-binding protein-β

UCH-L1:

Ubiquitin C-terminal hydrolase-L1

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Acknowledgements

This study is supported in part by the DOD grants W81XWH-12-1-0276 (WDD, MSW) and W81XWH-12-1-0277 (KKW) from the US Army.

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Correspondence to Zhihui Yang or Kevin K. W. Wang.

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The authors declare that they have no conflict of interest.

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Yang, Z., Bramlett, H.M., Moghieb, A. et al. Temporal Profile and Severity Correlation of a Panel of Rat Spinal Cord Injury Protein Biomarkers. Mol Neurobiol 55, 2174–2184 (2018). https://doi.org/10.1007/s12035-017-0424-7

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  • DOI: https://doi.org/10.1007/s12035-017-0424-7

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