As the brain is over 50% lipids, and traumatic brain injury (TBI) is the main cause of death among young adults and TBI victims often become drug addicts; We studied qualitative and quantitative lipids changes in brain tissue of a rat model of controlled cortical impact (CCI), over time (1, 3 and 7days post trauma), to understand progression of the pathology. The animals were divided into two groups control and CCI brains. We found lipid biomarkers that are reflected in CSF and plasma, and thus could be used for an early and rapid non invasive diagnosis and monitoring. Lipids distribution was mapped by mass spectrometric lipid imaging, to trace and follow lipids changes location in various areas of the brain. We invented a peptide drug, that when administered intravenously 30 minutes post trauma, stopped or significantly diminished progression of the damage. Intranasal administration within the same time frame gave an improved outcome, but was less effective. As our data turned out to be very promising, we believe that further work on the peptide drug would be beneficial. As the project is work intensive and requires expensive supplies, we are seeking funding for further testing of various dosages and regimen. Currently, we are preparing two manuscripts for publication for this project.

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Support Year
4
Fiscal Year
2016
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Indirect Cost
Name
National Institute on Drug Abuse
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Barbacci, Damon C; Roux, Aurelie; Muller, Ludovic et al. (2017) Mass Spectrometric Imaging of Ceramide Biomarkers Tracks Therapeutic Response in Traumatic Brain Injury. ACS Chem Neurosci 8:2266-2274
Roux, Aurelie; Muller, Ludovic; Jackson, Shelley N et al. (2016) Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury. J Neurosci Methods 272:19-32
Tovo-Rodrigues, L; Roux, A; Hutz, M H et al. (2014) Functional characterization of G-protein-coupled receptors: a bioinformatics approach. Neuroscience 277:764-79
Woods, Amina S; Colsch, Benoit; Jackson, Shelley N et al. (2013) Gangliosides and ceramides change in a mouse model of blast induced traumatic brain injury. ACS Chem Neurosci 4:594-600
Lenoir, Magalie; Tang, Jeremy S; Woods, Amina S et al. (2013) Rapid sensitization of physiological, neuronal, and locomotor effects of nicotine: critical role of peripheral drug actions. J Neurosci 33:9937-49
Woods, A S; Jackson, S N (2013) How adenylate cyclase choreographs the pas de deux of the receptors heteromerization dance. Neuroscience 238:335-44
Woods, Amina S; Jackson, Shelley N; Lewis, Ernest K et al. (2013) MALDI/post ionization-ion mobility mass spectrometry of noncovalent complexes of dopamine receptors' epitopes. J Proteome Res 12:1668-77
Barbacci, Damon; Jackson, Shelley N; Muller, Ludovic et al. (2012) Cellular membrane phospholipids act as a depository for quaternary amine containing drugs thus competing with the acetylcholine/nicotinic receptor. J Proteome Res 11:3382-9