title: Neuroproteomics: a biochemical means to discriminate the extent and modality of brain injury.
abstract: Diagnosis and treatment of stroke and traumatic brain injury remain significant health care challenges to society. Patient care stands to benefit from an improved understanding of the interactive biochemistry underlying neurotrauma pathobiology. In this study, we assessed the power of neuroproteomics to contrast biochemical responses following ischemic and traumatic brain injuries in the rat. A middle cerebral artery occlusion (MCAO) model was employed in groups of 30-min and 2-h focal neocortical ischemia with reperfusion. Neuroproteomes were assessed via tandem cation-anion exchange chromatography-gel electrophoresis, followed by reversed-phase liquid chromatography-tandem mass spectrometry. MCAO results were compared with those from a previous study of focal contusional brain injury employing the same methodology to characterize homologous neocortical tissues at 2 days post-injury. The 30-min MCAO neuroproteome depicted abridged energy production involving pentose phosphate, modulated synaptic function and plasticity, and increased chaperone activity and cell survival factors. The 2-h MCAO data indicated near complete loss of ATP production, synaptic dysfunction with degraded cytoarchitecture, more conservative chaperone activity, and additional cell survival factors than those seen in the 30-min MCAO model. The TBI group exhibited disrupted metabolism, but with retained malate shuttle functionality. Synaptic dysfunction and cytoarchitectural degradation resembled the 2-h MCAO group; however, chaperone and cell survival factors were more depressed following TBI. These results underscore the utility of neuroproteomics for characterizing interactive biochemistry for profiling and contrasting the molecular aspects underlying the pathobiological differences between types of brain injuries.
authors.affiliation: Department of Anatomy, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298-0709, USA. akottens@vcu.edu
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Ottens
authors.forename: Liliana
authors.initials: L
authors.lastname: Bustamante
authors.forename: Erin C
authors.initials: EC
authors.lastname: Golden
authors.forename: Changping
authors.initials: C
authors.lastname: Yao
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Hayes
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
authors.forename: Frank C
authors.initials: FC
authors.lastname: Tortella
authors.forename: Jitendra R
authors.initials: JR
authors.lastname: Dave
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002852:Chromatography, Ion Exchange; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D008297:Male; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D053719:Tandem Mass Spectrometry