Screening of biochemical and molecular mechanisms of secondary injury and repair in the brain after experimental blast-induced traumatic brain injury in rats

Patrick M. Kochanek, C. Edward Dixon, David K. Shellington, Samuel S. Shin, Hülya Bayir, Edwin K. Jackson, Valerian E. Kagan, Hong Q. Yan, Peter V. Swauger, Steven A. Parks, David V. Ritzel, Richard Bauman, Robert S.B. Clark, Robert H. Garman, Faris Bandak, Geoffrey Ling, Larry W. Jenkins

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Explosive blast-induced traumatic brain injury (TBI) is the signature insult in modern combat casualty care and has been linked to post-traumatic stress disorder, memory loss, and chronic traumatic encephalopathy. In this article we report 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 ∼25% mortality from apnea. Shams received identical anesthesia exposure. Rats were sacrificed at 2 or 24 h, and brain was sampled in the hippocampus and prefrontal cortex. Hippocampal samples were used to assess gene array (RatRef-12 Expression BeadChip; Illumina, Inc., San Diego, CA) and oxidative stress (OS; ascorbate, glutathione, low-molecular-weight thiols [LMWT], protein thiols, and 4-hydroxynonenal [HNE]). Cortical samples were used to assess neuroinflammation (cytokines, chemokines, and growth factors; Luminex Corporation, Austin, TX) and purines (adenosine triphosphate [ATP], adenosine diphosphate, adenosine, inosine, 2′-AMP [adenosine monophosphate], and 5′-AMP). Gene array revealed marked increases in astrocyte and neuroinflammatory markers at 24 h (glial fibrillary acidic protein, vimentin, and complement component 1) with expression patterns bioinformatically consistent with those noted in Alzheimer's disease and long-term potentiation. Ascorbate, LMWT, and protein thiols were reduced at 2 and 24 h; by 24 h, HNE was increased. At 2 h, multiple cytokines and chemokines (interleukin [IL]-1α, IL-6, IL-10, and macrophage inflammatory protein 1 alpha [MIP-1α]) were increased; by 24 h, only MIP-1α remained elevated. ATP was not depleted, and adenosine correlated with 2′-cyclic AMP (cAMP), and not 5′-cAMP. Our data reveal (1) gene-array alterations similar to disorders of memory processing and a marked astrocyte response, (2) OS, (3) neuroinflammation with a sustained chemokine response, and (4) adenosine production despite lack of energy failure - possibly resulting from metabolism of 2′-3′-cAMP. A robust biochemical/molecular response occurs after blast-induced mTBI, with the body protected from blast and the head constrained to limit motion.

Original languageEnglish (US)
Pages (from-to)920-937
Number of pages18
JournalJournal of neurotrauma
Issue number11
StatePublished - Jun 1 2013
Externally publishedYes


  • ATP
  • adenosine
  • antioxidant
  • ascorbate
  • axonal injury
  • chemokine
  • combat casualty care
  • cyclic AMP
  • cytokine
  • gene array
  • glutathione
  • improvised explosive device
  • lipid peroxidation
  • multiplex
  • post-traumatic stress disorder
  • purine

ASJC Scopus subject areas

  • Clinical Neurology


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