Abstract
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 h 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 the 190 identified brain metabolites was performed. Metabolites were divided into seven 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.
Highlights
Traumatic brain injury (TBI) is a major cause of long term disability worldwide with higher numbers of pediatric patients in the age range of 4–19 years (Faul et al, 2010; Brain Injury Association of America, 2014)
Neurotransmission (Chiron et al, 1992; Biagi et al, 2007; Hales et al, 2014), (Chugani et al, 1987), proportionally higher cell numbers, increased central nervous system (CNS) myelination (Dobbing and Sands, 1973), (Reiss et al, 1996; Paus et al, 2001) and a constantly evolving neurovascular activity (Biagi et al, 2007; Labarthe et al, 2009; Winter et al, 2011; Hales et al, 2014), These progressive changes lead to highly variable outcomes on the already broad TBI pathology, which depends on injury intensity and biomechanics (Park et al, 2008; Ma et al, 2019), making TBI classification in animal models of injury a current challenge
A top-down untargeted metabolite set enrichment analysis (MSEA) revealed a diverse set of affected metabolite sets in at least 25 different biochemical pathways that broadly related to amino acid, fatty acid, one-carbon/folate, neurotransmitter and energy metabolism (Chitturi et al, 2018)
Summary
Traumatic brain injury (TBI) is a major cause of long term disability worldwide with higher numbers of pediatric patients in the age range of 4–19 years (Faul et al, 2010; Brain Injury Association of America, 2014). Developmental differences in TBI outcomes can be attributed to intrinsic nature of the developing brain, presenting unique metabolism, cerebral blood flow (CBF), Neurochemical Profile of Developmental TBI neurotransmission (Chiron et al, 1992; Biagi et al, 2007; Hales et al, 2014), (Chugani et al, 1987), proportionally higher cell numbers, increased central nervous system (CNS) myelination (Dobbing and Sands, 1973), (Reiss et al, 1996; Paus et al, 2001) and a constantly evolving neurovascular activity (Biagi et al, 2007; Labarthe et al, 2009; Winter et al, 2011; Hales et al, 2014), These progressive changes lead to highly variable outcomes on the already broad TBI pathology, which depends on injury intensity and biomechanics (Park et al, 2008; Ma et al, 2019), making TBI classification in animal models of injury a current challenge.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
