PT  - JOURNAL ARTICLE
AU  - Michael A. Skinnider
AU  - Jason Rogalski
AU  - Seth Tigchelaar
AU  - Neda Manouchehri
AU  - Anna Prudova
AU  - Angela M. Jackson
AU  - Karina Nielsen
AU  - Jaihyun Jeong
AU  - Shalini Chaudhary
AU  - Katelyn Shortt
AU  - Ylonna Gallagher-Kurtzke
AU  - Kitty So
AU  - Allan Fong
AU  - Rishab Gupta
AU  - Elena B. Okon
AU  - Michael A. Rizzuto
AU  - Kevin Dong
AU  - Femke Streijger
AU  - Lise Belanger
AU  - Leanna Ritchie
AU  - Angela Tsang
AU  - Sean Christie
AU  - Jean-Marc Mac-Thiong
AU  - Christopher Bailey
AU  - Tamir Ailon
AU  - Raphaele Charest-Morin
AU  - Nicholas Dea
AU  - Jefferson R. Wilson
AU  - Sanjay Dhall
AU  - Scott Paquette
AU  - John Street
AU  - Charles G. Fisher
AU  - Marcel F. Dvorak
AU  - Casey Shannon
AU  - Christoph Borchers
AU  - Robert Balshaw
AU  - Leonard J. Foster
AU  - Brian K. Kwon
TI  - Proteomic portraits reveal evolutionarily conserved and divergent responses to spinal cord injury
AID  - 10.1101/2021.01.27.428528
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.27.428528
4099  - http://biorxiv.org/content/early/2021/01/28/2021.01.27.428528.short
4100  - http://biorxiv.org/content/early/2021/01/28/2021.01.27.428528.full
AB  - Despite the emergence of promising therapeutic approaches in preclinical studies, the failure of large-scale clinical trials leaves clinicians without effective treatments for acute spinal cord injury (SCI). These trials are hindered by their reliance on detailed neurological examinations to establish outcomes, which inflate the time and resources required for completion. Moreover, therapeutic development takes place in animal models whose relevance to human injury remains unclear. Here, we address these challenges through targeted proteomic analyses of CSF and serum samples from 111 acute SCI patients and, in parallel, a large animal (porcine) model of SCI. We develop protein biomarkers of injury severity and recovery, including a prognostic model of neurological improvement at six months with an AUC of 0.91, and validate these in an independent cohort. Through cross-species proteomic analyses, we dissect evolutionarily conserved and divergent aspects of the SCI response, and establish the CSF abundance of glial fibrillary acidic protein (GFAP) as a biochemical outcome measure in both humans and pigs. Our work opens up new avenues to catalyze translation by facilitating the evaluation of novel SCI therapies, while also providing a resource from which to direct future preclinical efforts.Competing Interest StatementThe authors have declared no competing interest.