title: Plasma micro-RNA biomarkers for diagnosis and prognosis after traumatic brain injury: A pilot study.
abstract: Prediction of post-concussive syndrome after apparent mild traumatic brain injury (TBI) and subsequent cognitive recovery remains challenging, with substantial limitations of current methods of cognitive testing. This pilot study aimed to determine if levels of micro ribonucleic acids (RNAs) circulating in plasma are altered following TBI, and if changes to levels of such biomarkers over time could assist in determination of prognosis after TBI. Patients were enrolled after TBI on presentation to the Emergency Department and allocated to three groups: A - TBI (physical trauma to the head), witnessed loss of consciousness, amnesia, GCS=15, a normal CT Brain and a recorded first pass after post-traumatic amnesia (PTA) scale; B TBI, witnessed LOC, amnesia, GCS=15, a normal CT brain and a PTA scale test fail and: C - TBI and initial GCS <13 on arrival to the ED. Venous blood was collected at three time points (arrival, day 5 and day 30). Isolation of cell-free total RNA was then assayed using a custom miRNA PCR array. Two micro-RNAs, mir142-3p and mir423-3p demonstrated potential clinical utility differentiating patients after mild head injury into those at greater risk of developing amnesia and therefore, post-concussive syndromes. In addition, these miRNA demonstrated a decrease in expression over time, possibly indicative of brain healing after the injury. Further evaluation of these identified miRNA markers with larger patient cohorts, correlation with clinical symptoms and analysis over longer time periods are essential next steps in developing objective markers of severity of TBI.
authors.affiliation: Emergency & Trauma Centre, The Alfred Hospital, Australia; National Trauma Research Institute, The Alfred Hospital, Australia; Department of Epidemiology & Preventive Medicine, Monash University, Australia. Electronic address: biswadev.mitra@monash.edu.
authors.forename: Biswadev
authors.initials: B
authors.lastname: Mitra
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Rau
authors.affiliation: National Trauma Research Institute, The Alfred Hospital, Australia.
authors.forename: Nanda
authors.initials: N
authors.lastname: Surendran
authors.affiliation: Emergency & Trauma Centre, The Alfred Hospital, Australia; National Trauma Research Institute, The Alfred Hospital, Australia.
authors.forename: James H
authors.initials: JH
authors.lastname: Brennan
authors.affiliation: National Trauma Research Institute, The Alfred Hospital, Australia.
authors.forename: Prasanthan
authors.initials: P
authors.lastname: Thaveenthiran
authors.affiliation: Glia Diagnostics, Australia.
authors.forename: Edmond
authors.initials: E
authors.lastname: Sorich
authors.affiliation: National Trauma Research Institute, The Alfred Hospital, Australia; Trauma Service, The Alfred Hospital, Australia.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Fitzgerald
authors.affiliation: Department of Surgery, Monash University, Melbourne, Australia; Department of Neurosurgery, The Alfred Hospital, Melbourne, Australia; Department of Surgery, F. Edward Hébert School of Medicine, Uniformed Services University of The Health Sciences, Bethesda, MD, USA.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Rosenfeld
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT, USA.
authors.forename: Sarjubhai A
authors.initials: SA
authors.lastname: Patel
mesh_terms: D000328:Adult; D000368:Aged; D000647:Amnesia / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D010865:Pilot Projects; D038223:Post-Concussion Syndrome / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D011379:Prognosis; D055815:Young Adult
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: Biomarkers; Brain concussion; Brain injuries; Disease progression; Humans; Micro RNA