{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/12676"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/12676","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Longitudinal Metabolic and Proteomic Changes Studied in an Experimental Model of Traumatic Brain Injury","abstract":"Traumatic brain injury (TBI) causes a series of complex molecular events resulting in long-term neurological deficits. Currently, it is not possible to predict which, if any, deficits might occur or when they might occur in an individual. Substantial challenges to the development of treatment strategies include the complexity and heterogeneity of the clinical presentation coupled with limited understanding of chronic disease progression. To address these issues, we hypothesize that longitudinal metabolomic and proteomic studies may reveal mechanistic details explaining secondary injury after TBI and the potential timing of the events. We have conducted these studies using complementary mass spectrometry approaches and determined significant molecular events at time points between 24 h and 1 year post TBI. In the acute period, the most significant events are increased utilization of glutamate oxidation, perturbations to glucose and one carbon metabolism, energy failure, impairment of antioxidant capacity, blood-brain barrier BBB breach and elevated glial acidic fibirillary protein (GFAP). GFAP levels remain elevated in the cortex and hippocampus at 3 months and return close to normal by 6 months. Surprisingly, GFAP increases in the cortex at 1 year for an unknown reason. By 2 weeks many of the metabolic perturbations have resolved. Potential interventions suggested from these metabolic studies include, nicotinamide riboside, lipoic acid, and DHAA. They would probably be most efficacious if given soon after the initial injury. ApoE spikes at 2 weeks along with Slc1a2, in both the cortex and hippocampus coinciding with normalization of cellular metabolism. Endogenous repair processes begin in the cortex at 2 weeks and continue at 3 months post injury. In the hippocampus, activation of Nrf2 pathways is observe at the 3 month time point and proteins related to neurogenesis/repair processes are found at the 6 month time point. Finally, at 1 year, in both the cortex and hippocampus we observe variable changes in glutamate transporter Slc1a2 and Gabra2 in the cortex, suggesting that the balance between glutamate and GABA is unresolved influx even 1 year post injury. At these later time points (> 2 weeks), interventions aimed at enhancing reparative processes like ApoE mimetics, or pharmacologic modulation of the Nrf2 pathway could be beneficial.","abstract_html":"Traumatic brain injury (TBI) causes a series of complex molecular events resulting in long-term neurological deficits. Currently, it is not possible to predict which, if any, deficits might occur or when they might occur in an individual. Substantial challenges to the development of treatment strategies include the complexity and heterogeneity of the clinical presentation coupled with limited understanding of chronic disease progression. To address these issues, we hypothesize that longitudinal metabolomic and proteomic studies may reveal mechanistic details explaining secondary injury after TBI and the potential timing of the events. We have conducted these studies using complementary mass spectrometry approaches and determined significant molecular events at time points between 24 h and 1 year post TBI. In the acute period, the most significant events are increased utilization of glutamate oxidation, perturbations to glucose and one carbon metabolism, energy failure, impairment of antioxidant capacity, blood-brain barrier BBB breach and elevated glial acidic fibirillary protein (GFAP). GFAP levels remain elevated in the cortex and hippocampus at 3 months and return close to normal by 6 months. Surprisingly, GFAP increases in the cortex at 1 year for an unknown reason. By 2 weeks many of the metabolic perturbations have resolved. Potential interventions suggested from these metabolic studies include, nicotinamide riboside, lipoic acid, and DHAA. They would probably be most efficacious if given soon after the initial injury. ApoE spikes at 2 weeks along with Slc1a2, in both the cortex and hippocampus coinciding with normalization of cellular metabolism. Endogenous repair processes begin in the cortex at 2 weeks and continue at 3 months post injury. In the hippocampus, activation of Nrf2 pathways is observe at the 3 month time point and proteins related to neurogenesis/repair processes are found at the 6 month time point. Finally, at 1 year, in both the cortex and hippocampus we observe variable changes in glutamate transporter Slc1a2 and Gabra2 in the cortex, suggesting that the balance between glutamate and GABA is unresolved influx even 1 year post injury. At these later time points (> 2 weeks), interventions aimed at enhancing reparative processes like ApoE mimetics, or pharmacologic modulation of the Nrf2 pathway could be beneficial.","abstract_has_math":false,"creators":["Sowers, James Lai"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Neuroscience (Doctoral)","degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-05","date_published":"2020-05","updated_at":"2026-07-24T05:51:09Z","subjects":["Biology, Neuroscience","Chemistry, Biochemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2152.3/12676","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Sowers, James Lai"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-05-05T15:15:58Z"]},{"key":"dc:date.issued","label":"Date","values":["2020-05"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Neuroscience (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology, Neuroscience","Chemistry, Biochemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/2152.3/12676"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Traumatic brain injury (TBI) causes a series of complex molecular events resulting in long-term neurological deficits. Currently, it is not possible to predict which, if any, deficits might occur or when they might occur in an individual. Substantial challenges to the development of treatment strategies include the complexity and heterogeneity of the clinical presentation coupled with limited understanding of chronic disease progression. To address these issues, we hypothesize that longitudinal metabolomic and proteomic studies may reveal mechanistic details explaining secondary injury after TBI and the potential timing of the events. We have conducted these studies using complementary mass spectrometry approaches and determined significant molecular events at time points between 24 h and 1 year post TBI. In the acute period, the most significant events are increased utilization of glutamate oxidation, perturbations to glucose and one carbon metabolism, energy failure, impairment of antioxidant capacity, blood-brain barrier BBB breach and elevated glial acidic fibirillary protein (GFAP). GFAP levels remain elevated in the cortex and hippocampus at 3 months and return close to normal by 6 months. Surprisingly, GFAP increases in the cortex at 1 year for an unknown reason. By 2 weeks many of the metabolic perturbations have resolved. Potential interventions suggested from these metabolic studies include, nicotinamide riboside, lipoic acid, and DHAA. They would probably be most efficacious if given soon after the initial injury. ApoE spikes at 2 weeks along with Slc1a2, in both the cortex and hippocampus coinciding with normalization of cellular metabolism. Endogenous repair processes begin in the cortex at 2 weeks and continue at 3 months post injury. In the hippocampus, activation of Nrf2 pathways is observe at the 3 month time point and proteins related to neurogenesis/repair processes are found at the 6 month time point. Finally, at 1 year, in both the cortex and hippocampus we observe variable changes in glutamate transporter Slc1a2 and Gabra2 in the cortex, suggesting that the balance between glutamate and GABA is unresolved influx even 1 year post injury. At these later time points (> 2 weeks), interventions aimed at enhancing reparative processes like ApoE mimetics, or pharmacologic modulation of the Nrf2 pathway could be beneficial."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Longitudinal Metabolic and Proteomic Changes Studied in an Experimental Model of Traumatic Brain Injury"]}]}],"canonical_facts":{"dc:creator":["Sowers, James Lai"],"dc:date.accessioned":["2025-05-05T15:15:58Z"],"dc:date.issued":["2020-05"],"dc:description.abstract":["Traumatic brain injury (TBI) causes a series of complex molecular events resulting in long-term neurological deficits. Currently, it is not possible to predict which, if any, deficits might occur or when they might occur in an individual. Substantial challenges to the development of treatment strategies include the complexity and heterogeneity of the clinical presentation coupled with limited understanding of chronic disease progression. To address these issues, we hypothesize that longitudinal metabolomic and proteomic studies may reveal mechanistic details explaining secondary injury after TBI and the potential timing of the events. We have conducted these studies using complementary mass spectrometry approaches and determined significant molecular events at time points between 24 h and 1 year post TBI. In the acute period, the most significant events are increased utilization of glutamate oxidation, perturbations to glucose and one carbon metabolism, energy failure, impairment of antioxidant capacity, blood-brain barrier BBB breach and elevated glial acidic fibirillary protein (GFAP). GFAP levels remain elevated in the cortex and hippocampus at 3 months and return close to normal by 6 months. Surprisingly, GFAP increases in the cortex at 1 year for an unknown reason. By 2 weeks many of the metabolic perturbations have resolved. Potential interventions suggested from these metabolic studies include, nicotinamide riboside, lipoic acid, and DHAA. They would probably be most efficacious if given soon after the initial injury. ApoE spikes at 2 weeks along with Slc1a2, in both the cortex and hippocampus coinciding with normalization of cellular metabolism. Endogenous repair processes begin in the cortex at 2 weeks and continue at 3 months post injury. In the hippocampus, activation of Nrf2 pathways is observe at the 3 month time point and proteins related to neurogenesis/repair processes are found at the 6 month time point. Finally, at 1 year, in both the cortex and hippocampus we observe variable changes in glutamate transporter Slc1a2 and Gabra2 in the cortex, suggesting that the balance between glutamate and GABA is unresolved influx even 1 year post injury. At these later time points (> 2 weeks), interventions aimed at enhancing reparative processes like ApoE mimetics, or pharmacologic modulation of the Nrf2 pathway could be beneficial."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://hdl.handle.net/2152.3/12676"],"dc:subject":["Biology, Neuroscience","Chemistry, Biochemistry"],"dc:title":["Longitudinal Metabolic and Proteomic Changes Studied in an Experimental Model of Traumatic Brain Injury"],"dc:type":["Thesis"],"thesis:degree_name":["Neuroscience (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:51:09Z"}