Screening of Biochemical and Molecular Mechanisms of Secondary Injury and Repair in the Brain after Experimental Blast-Induced Traumatic Brain Injury in Rats
Abstract
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 biochemical/molecular 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2013
- Accession Number
- ADA574852
Entities
People
- C. E. Dixon
- David K. Shellington
- Edwin K. Jackson
- Hong Q. Yan
- Hülya Bayır
- Patrick M. Kochanek
- Peter V. Swauger
- Samuel S. Shin
- Steven A. Parks
- Valerian E. Kagan
Organizations
- Uniformed Services University of the Health Sciences