Original Research ARTICLE
Consolidated biochemical profile of subacute stage traumatic brain injury in early development
- 1Radiology, Rutgers Biomedical and Health Sciences, United States
- 2Pharmacology Physiology and Neuroscience, Rutgers Biomedical and Health Sciences, United States
- 3Molecular, Cell and Systems Biology, University of California, Riverside, United States
Traumatic brain injury (TBI) in general has varied neuropathological consequences depending upon the intensity and biomechanics of the injury. Furthermore, in pediatric TBI, intrinsic developmental changes add further complexity, necessitating a biochemical dimension for improved TBI characterization. In our earlier study investigating the subacute stage TBI metabolome (72 hours post-injury) in a developmental rat model, significant ipsilateral brain biochemical changes occurred across 25 metabolite sets as determined by metabolite set enrichment analysis (MSEA). The broad metabolic perturbation was accompanied by behavioral deficits and neuronal loss across the ipsilateral hemisphere containing the injury epicenter. In order to obtain a consolidated biochemical profile of the TBI assessment, a subgrouping of the190 identified brain metabolites was performed. Metabolites were divided into 7 major subgroups: oxidative energy/mitochondrial, glycolysis/pentose phosphate pathway, fatty acid, amino acid, neurotransmitters/neuromodulators, one-carbon/folate and other metabolites. Subgroups were based on the chemical nature and association with critically altered biochemical pathways after TBI as obtained from our earlier untargeted analysis. Each metabolite subgroup extracted from the ipsilateral sham and TBI brains were modeled using multivariate partial least square discriminant analysis (PLS-DA) with the model accuracy used as a measurable index of TBI neurochemical impact. Volcano plots of each subgroup, corrected for multiple comparisons, determined the TBI neurochemical specificity. The results provide a ranked biochemical profile along with specificity of changes after developmental TBI, enabling a consolidated biochemical template for future classification of different TBI intensities and injury types in animal models.
Keywords: Traumatic Brain Injury, Mitochondria, Metabolomics, Glycolysis, pediatric, TCA cycle, neurodegeneration, Glutathione, N acetyl aspartic acid, rat models
Received: 12 Apr 2018;
Accepted: 15 Apr 2019.
Edited by:Julijana Ivanisevic, Université de Lausanne, Switzerland
Reviewed by:Tao Huan, University of British Columbia, Canada
Jun-Song Wang, Nanjing University of Science and Technology, China
Jennifer McGuire, University of Cincinnati, United States
Copyright: © 2019 Chitturi, Li, Santhakumar and Kannurpatti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Dr. Sridhar Kannurpatti, Rutgers Biomedical and Health Sciences, Radiology, Newark, United States, email@example.com