title: Transcriptional profiling in rat hair follicles following simulated Blast insult: a new diagnostic tool for traumatic brain injury.
abstract: With wide adoption of explosive-dependent weaponry during military activities, Blast-induced neurotrauma (BINT)-induced traumatic brain injury (TBI) has become a significant medical issue. Therefore, a robust and accessible biomarker system is in demand for effective and efficient TBI diagnosis. Such systems will also be beneficial to studies of TBI pathology. Here we propose the mammalian hair follicles as a potential candidate. An Advanced Blast Simulator (ABS) was developed to generate shock waves simulating traumatic conditions on brains of rat model. Microarray analysis was performed in hair follicles to identify the gene expression profiles that are associated with shock waves. Gene set enrichment analysis (GSEA) and sub-network enrichment analysis (SNEA) were used to identify cell processes and molecular signaling cascades affected by simulated bomb blasts. Enrichment analyses indicated that genes with altered expression levels were involved in central nervous system (CNS)/peripheral nervous system (PNS) responses as well as signal transduction including Ca2+, K+-transportation-dependent signaling, Toll-Like Receptor (TLR) signaling and Mitogen Activated Protein Kinase (MAPK) signaling cascades. Many of the pathways identified as affected by shock waves in the hair follicles have been previously reported to be TBI responsive in other organs such as brain and blood. The results suggest that the hair follicle has some common TBI responsive molecular signatures to other tissues. Moreover, various TBI-associated diseases were identified as preferentially affected using a gene network approach, indicating that the hair follicle may be capable of reflecting comprehensive responses to TBI conditions. Accordingly, the present study demonstrates that the hair follicle is a potentially viable system for rapid and non-invasive TBI diagnosis.
authors.affiliation: Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, Ontario, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, Ontario, Canada.
authors.forename: Lisa
authors.initials: L
authors.lastname: Carnduff
authors.affiliation: Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, Ontario, Canada.
authors.forename: Grant
authors.initials: G
authors.lastname: Norman
authors.affiliation: Defence Research and Development Canada - Suffield, Medicine Hat, Alberta, Canada.
authors.forename: Tyson
authors.initials: T
authors.lastname: Josey
authors.affiliation: Defence Research and Development Canada - Suffield, Medicine Hat, Alberta, Canada.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Defence Research and Development Canada - Suffield, Medicine Hat, Alberta, Canada.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Sawyer
authors.affiliation: University of New Brunswick and Canadian River Institute, Fredericton, New Brunswick, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martyniuk
authors.affiliation: Chemistry and Chemical Engineering Department, Royal Military College of Canada, Kingston, Ontario, Canada.
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Langlois
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001753:Blast Injuries / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005107:Explosions; D015870:Gene Expression; D020869:Gene Expression Profiling; D018859:Hair Follicle / Q000378:metabolism*; D019220:High-Energy Shock Waves; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D046228:Microarray Analysis; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D051193:Toll-Like Receptors; D020928:Mitogen-Activated Protein Kinases