title: CSF Bcl-2 and cytochrome C temporal profiles in outcome prediction for adults with severe TBI.
abstract: The biochemical cascades associated with cell death after traumatic brain injury (TBI) involve both pro-survival and pro-apoptotic proteins. We hypothesized that elevated cerebrospinal fluid (CSF) Bcl-2 and cytochrome C (CytoC) levels over time would reflect cellular injury response and predict long-term outcomes after TBI. Cerebrospinal fluid Bcl-2 and CytoC levels were measured for 6 days after injury for adults with severe TBI (N=76 subjects; N=277 samples). Group-based trajectory analysis was used to generate distinct temporal biomarker profiles that were compared with Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS) scores at 6 and 12 months after TBI. Subjects with persistently elevated temporal Bcl-2 and CytoC profiles compared with healthy controls had the worst outcomes at 6 and 12 months (P≤0.027). Those with CytoC profiles near controls had better long-term outcomes, and those with declining CytoC levels over time had intermediate outcomes. Subjects with Bcl-2 profiles that remained near controls had better outcomes than those with consistently elevated Bcl-2 profiles. However, subjects with Bcl-2 values that started near controls and steadily rose over time had 100% good outcomes by 12 months after TBI. These results show the prognostic value of Bcl-2 and CytoC profiles and suggest a dynamic apoptotic and pro-survival response to TBI.
authors: Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. wagnerak@upmc.edu
authors: Amy K
authors: AK
authors: Wagner
authors: Krutika B
authors: KB
authors: Amin
authors: Christian
authors: C
authors: Niyonkuru
authors: Brett A
authors: BA
authors: Postal
authors: Emily H
authors: EH
authors: McCullough
authors: Haishin
authors: H
authors: Ozawa
authors: C Edward
authors: CE
authors: Dixon
authors: Hulya
authors: H
authors: Bayir
authors: Robert S
authors: RS
authors: Clark
authors: Patrick M
authors: PM
authors: Kochanek
authors: Anthony
authors: A
authors: Fabio
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000628:therapy; D015331:Cohort Studies; D045304:Cytochromes c / Q000134:cerebrospinal fluid*; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000134:cerebrospinal fluid*; D016896:Treatment Outcome
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D045304:Cytochromes c