Mitochondrial targeted neuron focused genes in hippocampus of rats with traumatic brain injury
Pushpa Sharma1, Yan A Su2, Erin S Barry3, Neil E Grunberg3, Prasanth S Ariyannur1, Zhang Lei4
1 Department of Anesthesiology, Uniformed Services University of the Health Sciences, Rockville, Maryland, USA
2 Department of Gene and Protein Biomarkers, GenPro Markers, Inc, Rockville, Maryland, USA
3 Department of Medical and Clinical Psychology, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
4 Department of Psychiatry, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, Bethesda, MD, USA
Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814
Source of Support: None, Conflict of Interest: None
Context: Mild traumatic brain injury (mTBI) represents a major health problem in civilian populations as well as among the military service members due to (1) lack of effective treatments, and (2) our incomplete understanding about the progression of secondary cell injury cascades resulting in neuronal cell death due to deficient cellular energy metabolism and damaged mitochondria.
Aims: The aim of this study was to identify and delineate the mitochondrial targeted genes responsible for altered brain energy metabolism in the injured brain.
Settings and Design: Rats were either grouped into naοve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed up for 7 days.
Materials and Methods: Rats were either grouped into naοve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed for 7 days. The severity of brain injury was evaluated by the neurological severity scale-revised (NSS-R) at 3 and 5 days post TBI and immunohistochemical analyses at 7 days post TBI. The expression profiles of mitochondrial-targeted genes across the hippocampus from TBI and naÏe rats were also examined by oligo-DNA microarrays.
Results: NSS-R scores of TBI rats (5.4 ± 0.5) in comparison to naÏe rats (3.9 ± 0.5) and H and E staining of brain sections suggested a mild brain injury. Bioinformatics and systems biology analyses showed 31 dysregulated genes, 10 affected canonical molecular pathways including a number of genes involved in mitochondrial enzymes for oxidative phosphorylation, mitogen-activated protein Kinase (MAP), peroxisome proliferator-activated protein (PPAP), apoptosis signaling, and genes responsible for long-term potentiation of Alzheimer's and Parkinson's diseases.
Conclusions: Our results suggest that dysregulated mitochondrial-focused genes in injured brains may have a clinical utility for the development of future therapeutic strategies aimed at the treatment of TBI.