title: Identification of plasma biomarkers of TBI outcome using proteomic approaches in an APOE mouse model.
abstract: The current lack of diagnostic and prognostic biomarkers for traumatic brain injury (TBI) confounds treatment and management of patients and is of increasing concern as the TBI population grows. We have generated plasma proteomic profiles from mice receiving TBI by controlled cortical impact at either 1.3 mm or 1.8 mm depth, comparing these against those of sham injured-animals to identify plasma biomarkers specific to mild or severe TBI at 24 hours, 1 month, or 3 months post-injury. To identify possible prognostic biomarkers, we used apolipoprotein E (APOE)3 and APOE4 transgenic mice, which demonstrate relatively favorable and unfavorable outcomes respectively, following TBI. Using a quantitative proteomics approach (isobaric tagging for relative and absolute quantitation--iTRAQ) we have identified proteins that are significantly modulated as a function of TBI and also in response to the TBI*APOE genotype interaction, the latter representing potential prognostic biomarkers. These preliminary data clearly demonstrate plasma protein changes that are not only injury dependent but also interaction dependent. Importantly, these results demonstrate the presence of TBI-dependent and interaction-dependent plasma proteins at a 3-month time point, which is a considerable time post-injury in the mouse model, and will potentially be of significance for combat veterans receiving assessment at extended periods post-injury. Furthermore, our identification of clusters of functionally related proteins indicates disturbance of particular biological modules, which potentially increases their value beyond that of solitary biomarkers.
authors: Roskamp Institute, Sarasota, Florida 34243, USA. fcrawford@rfdn.org
authors: Fiona
authors: F
authors: Crawford
authors: Gogce
authors: G
authors: Crynen
authors: Jon
authors: J
authors: Reed
authors: Benoit
authors: B
authors: Mouzon
authors: Alex
authors: A
authors: Bishop
authors: Benjamin
authors: B
authors: Katz
authors: Scott
authors: S
authors: Ferguson
authors: John
authors: J
authors: Phillips
authors: Vani
authors: V
authors: Ganapathi
authors: Venkatarajan
authors: V
authors: Mathura
authors: Allen
authors: A
authors: Roses
authors: Michael
authors: M
authors: Mullan
mesh_terms: D000818:Animals; D053318:Apolipoprotein E3 / Q000737:chemistry* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000737:chemistry* / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000737:chemistry*; D001930:Brain Injuries / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011379:Prognosis; D040901:Proteomics / Q000379:methods*; D020127:Recovery of Function
chemical_list: D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D015415:Biomarkers; D001798:Blood Proteins