In the initial study, a controlled cortical impact (CCI) injury model in adult male rats were used to study the progression of the pathology resulting from TBI up to 7 days post injury. MSI with AgNPs was used to locate, analyze and study the changes in brain lipid composition at different time points. The impact was centered 2.04 mm posterior to bregma and 3.0 mm left of the midline 2.04 mm, Fig. 50 in Paxinos and Watson rat brain atlas. MSI analysis was conducted in both positive and negative ion mode in the injured coronal level. 37 lipids were imaged in positive ion mode, including 4 ceramides (CER), 9 diacylglycerols (DAG), 8 cholesteryl esters (CE), 13 galactosyl ceramides(GALCER), 2 phosphatidylcholines (PC) and cholesterol (CHL), while 56 lipids were imaged in negative ion mode, including 8 sphingomyelins (SM), 19 phosphatidylethanolamines (PE), 6 phosphatidylinositols (PI) and 23 sulfatides (ST). Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day afterthe injury whereas other lipids changes occurred between 3 and 7 days post injury. An additional study was conducted using the same animal model and a novel thearuptic peptide to observe the changes produced in lipid biomarkers. Adult male SpragueDawley rats received one strike and were euthanized 3 days post trauma. Brain MS images showed increase in ceramides in CCI animals compared to control as well as significant reduction in ceramides in CCI treated animals, demonstrating therapeutic effect of a peptide agonist. The data also suggests the presence of diffuse changes outside of the injured area. These results shed light on the extent of biochemical and structural changes in the brain after traumatic brain injury and could help to evaluate the efficacy of treatments.
