Traumatic Brain Injury
Conditions
Brief summary
Despite the decline in fatal traumatic brain injury (TBI) incidence in recent years, TBI morbidity remains a public health challenge and is the leading cause of disability in the United States. Detailed knowledge of the metabolic alterations following TBI will provide a significant advancement to our understanding of the hypometabolic response to TBI, which is key information for the future development and testing of novel therapeutic interventions that by-pass or compensate for the metabolic dysfunction. The goal of this study is to determine the clinical utility of in vivo 13C MRS to identify specific metabolic alterations following TBI. We hypothesize that following TBI, metabolic pathways are altered causing an incomplete oxidative of glucose in neurons and astrocytes resulting in a decrease in cerebral metabolism.
Detailed description
Despite the decline in fatal traumatic brain injury (TBI) incidence in recent years, TBI morbidity remains a public health challenge and is the leading cause of disability in the United States To combat these effects, new research is needed to identify mechanisms of injury that will lead to potential targets for therapeutic interventions that improve neurological outcome. One promising area of research is the cerebral metabolic dysfunction following TBI. Studies of post-traumatic cerebral metabolism have shown that cerebral metabolic rate of glucose (CMRglc) decreases for a period of days, weeks or months after injury with the duration and degree of hypometabolism correlating to level of consciousness and a strong predictor of long-term neurological outcome. However, specific changes in intermediary carbohydrate metabolic pathways have not yet been identified. In addition, the role of astrocyte metabolism in the post-injury metabolism has not been studied. This study uses in vivo 13C magnetic resonance spectroscopy (MRS) at 3 Tesla, a novel method in the clinical study of TBI, to non-invasively study the metabolic fate and flux of glucose (metabolized in both neurons and astrocytes) and acetate (metabolized in astrocytes) through metabolic pathways during the hypometabolic period.
Interventions
DIAGNOSTIC_TEST13C magnetic resonance spectroscopy
acquisition of 13C MR spectroscopy in the brain
Sponsors
Loma Linda University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Subjects will be at least 18 years of age without gender or ethnic restrictions. 2. Severe accidental TBI defined as the lowest post-resuscitation GCS \< 8 prior to administration of sedatives or paralytics. 3. Eligibility for MRI per routine screening checklist.
Exclusion criteria
1. History of neurosurgical intervention, excluding the placement of ventriculostomy shunt 2. History of a prior known brain injury with associated loss of consciousness. 3. History of a known neurological disorder prior to qualifying injury. 4. History of psychiatric disorder. 5. History of diabetes or current unstable serum glucose level. 6. Renal insufficiency or known history of kidney disease. 7. Known contraindication to MRI such as, pacemaker, pregnancy, and/or other non-MR compatible implanted device.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Detection of 13C Enriched Cerebral Metabolites | 5 years | Direct detection, localized in vivo 13C MRS will be used to measure the 13C enrichment of glutamate and glutamine following an infusion of 30% isotopically enriched \[1-13C\] glucose and \[1, 2-13C2\] acetate. |
Participant flow
Recruitment details
Participants were recruited from medical, surgical, or neurological services of LLUMC. Non-injured participants were recruited from MRI staff, Loma Linda University student or Resident populations
Participants by arm
| Arm | Count |
|---|---|
| Traumatic Brain Injury Participants with TBI undergoing 13C Magnetic resonance (MR) spectroscopy. | 0 |
| Control control (non-injured) participants undergoing 13C Magnetic resonance (MR) spectroscopy. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | Total | Control | Traumatic Brain Injury |
|---|---|---|---|
| Age, Continuous | 33 years STANDARD_DEVIATION 7.71 | 33 years STANDARD_DEVIATION 7.71 | — |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment United States | 9 participants | 9 participants | — |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 9 |
| other Total, other adverse events | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Detection of 13C Enriched Cerebral Metabolites
Direct detection, localized in vivo 13C MRS will be used to measure the 13C enrichment of glutamate and glutamine following an infusion of 30% isotopically enriched \[1-13C\] glucose and \[1, 2-13C2\] acetate.
Time frame: 5 years
Population: We were not successful in out attempt to collect localized in vivo 13C MRS thus there were no metabolite enrichments to measure and include in the measure data table.