Recent evidence suggest that lipids circulating in blood are derived in part from the central nervous system, with levels of specific lipid species changing in subjects suffering from a variety of neurodegenerative conditions. Of specific relevance to this proposal, recent studies have shown changes in blood lipids in patients with mild cognitive impairments associated with Alzheimer’s disease or Parkinsonism (PD) or in psychiatric conditions such as major depression (with unique lipid profiles for each condition). Moreover, longitudinal studies have shown that plasma lipid profiles could be prognostic indicators for later neurocognitive declines. These results suggest that mild traumatic brain injury (mTBI), a condition in which localized neuroinflammation and loss of neural tissues occurs, will also be accompanied by changes in circulating lipids originating from injured or degenerating neural tissues. Analysis of peripheral blood lipid profiles should both provide insights into the neurochemical pathology of brain damage after mTBI, may be useful as prognostic indicators for functional improvement or decline, and as surrogate measures for neural damage and repair. Altered lipid profiles might be utilized as surrogate endpoints for the evaluation of therapies or as diagnostic criteria. In this application we propose to evaluate blood lipid profiles from wellcharacterized TBI subjects who have contributed samples to the CNRM Biospecimen Repository (BR), comparing the lipid profiles in subjects soon after a mTBI (with MRI confirmation of mild brain injury and additional subjects with negative MRI scans) with those from control subjects without TBI.
Lipid profiles generated by mass-spectrometric analysis of plasma samples from 30 subjects represented in the CNRM BR with a recent (<72 hr) mTBI confirmed by positive MRI scans will be compared with lipid profiles from an age and gender matched group of 30 subjects presenting with mTBI injury (<72 hrs), but with negative MRI scans, and with 30 similar age and gender matched group of control subject with no reported TBI. The objective is to correlate changes in specific lipids or lipid profiles with MRI evidence of injury type, severity and/or location, and clinical outcomes at later time points. Under specific aim #2, blood samples will also be taken from the MRI positive and MRI-negative mTBI groups (30 subjects each) at later times points (3 months to 2 years after mTBI). These samples will be analyzed to determine the temporal stability of plasma lipid profiles in the same subjects, and to associate changes in lipid profiles with recovery from TBI. Finally, under specific aim #3 we will identify a group of 30 military subjects with history of prior TBI (subjects with blast-related TBI) experienced 3 months to 2 years prior to the time of blood sampling. The lipid profiles of these subjects will be compared with the lipid profiles obtained from civilian TBI subjects with impact-related TBIs at roughly equivalent time periods post injury. The objective here is to determine if plasma lipid profiles of military subjects with mTBI resulting from either impact-related injury or a blast injury are similar to the lipid profiles in the civilian subjects.
We hypothesize that distinct changes in plasma lipid profiles will be associated with severity of TBI and will change in a time-dependent manner following mTBI, reflecting both the severity and nature of the brain injury, and trajectory of recovery. Lipid profile changes will provide insight into the mechanisms of neural injury and repair, should facilitate diagnosis of mTBI, and may provide surrogate measures to monitor neural repair in response to intervention.
Age; Alzheimer's Disease; Biological Markers; Biological Markers; Blast Cell; Blast Injuries; Blood; blood lipid; Blood specimen; Brain Injuries; Central Nervous System Part; Clinical; Diagnosis; Diagnostic; experience; functional improvement; Gender; injured; Injury; injury and repair; insight; Intervention; Lipids; Location; Longitudinal Studies; Magnetic Resonance Imaging; Major Depressive Disorder; Matched Group; Measures; mild cognitive impairment; Military Personnel; Monitor; MRI Scans; Nature; Nerve Degeneration; nerve injury; neurochemistry; Neurocognitive; neuroinflammation; Outcome; Parkinsonian Disorders; Pathology; Patients; peripheral blood; Plasma; Prognostic Marker; Recording of previous events; Recovery; relating to nervous system; repaired; Reporting; repository; response; Sampling; Severities; Surrogate Endpoint; Therapy Evaluation; Time; Tissues; Traumatic Brain Injury