Screening of Biochemical and Molecular Mechanisms of Secondary Injury and Repair in the Brain after Experimental Blast-Induced Traumatic Brain Injury in Rats
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD
Pagination or Media Count:
Explosive Blast-induced traumatic brain injury TBI is the signature insult in modern combat casualty care and has been linked to posttraumatic stress disorder, memory loss, and chronic traumatic encephalopathy. We reported on blast induced mild TBI mTBI characterized by fiber-tract degeneration and axonal injury revealed by cupric silver staining in adult male rats after head only exposure to 35 PSI in a helium-driven shock tube with head restraint. We now explore pathways of secondary injury and repair using biochemicalmolecular strategies. Injury produced approx. 25 mortality from apnea. Shams received identical anesthesia exposure. Rats were sacrificed at 2h or 24h and brain sampled in hippocampus and pre-frontal cortex. Hippocampal samples were used to assess gene array RatRef-12 Expression BeadChip and oxidative stress ascorbate, glutathione GSH, low molecular weight thiols LMWT, protein thiols, and 4-hydroxynonenal HNE. Cortical samples were used to assess neuroinflammation cytokines, chemokines, and growth factors Luminex and purines ATP, ADP, adenosine, inosine, 2 -AMP, and 5 -AMP. Gene array revealed marked increases in astrocyte and neuroinflammatory markers at 24h GFAP, Vimentin, complement component 1 with expression patterns bioinformatically consistent with those seen in Alzheimer s disease and long-term potentiation. Ascorbate, LMWT, and protein thiols were reduced at 2 and 24h by 24h HNE was increased. At 2h, multiple cytokines and chemokines IL-1alpha, IL-6, IL-10, MIP-1alpha, were increased by 24h only MIP-1alpha remained elevated. ATP was not depleted and adenosine correlated with 2 - not 5 -cAMP. Our data reveal 1 gene array alterations similar to disorders of memory processing and a marked astrocyte response, 2 oxidative stress, 2 neuroinflammation with a sustained chemokine response, and 3 adenosine production despite lack of energy failure possibly resulting from metabolism of 2 -3 -cAMP.
- Medicine and Medical Research