Overpressure blast injury-induced oxidative stress and neuroinflammation response in rat frontal cortex and cerebellum

Hale Z. Toklu, Zhihui Yang, Sehkar Oktay, Yasemin Sakarya, Nataliya Kirichenko, Michael K. Matheny, Judy Muller-Delp, Kevin Strang, Philip J. Scarpace, Kevin K.W. Wang, Nihal Tümer

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background & aim Overpressure blast-wave induced brain injury (OBI) and its long-term neurological outcome pose significant concerns for military personnel. Our aim is to investigate the mechanism of injury due to OBI. Methods Rats were divided into 3 groups: (1) Control, (2) OBI (exposed 30 psi peak pressure, 2–2.5 ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24 h post injury. Results The neurological examination score was worse in OBI and r-OBI (4.2 ± 0.6 and 3.7 ± 0.5, respectively) versus controls (0.7 ± 0.2). A significant positive correlation between lung and brain edema was found. Malondialdehyde (index for lipid peroxidation), significantly increased in OBI and r-OBI groups in cortex (p < 0.05) and cerebellum (p < 0.01–0.001). The glutathione (endogenous antioxidant) level decreased in cortex (p < 0.01) and cerebellum (p < 0.05) of r-OBI group when compared with the controls. Myeloperoxidase activity indicating neutrophil infiltration, was significantly (p < 0.01–0.05) elevated in r-OBI. Additionally, tissue thromboplastin activity, a coagulation marker, was elevated, indicating a tendency to bleed. NGF and NF-κB proteins along with Iba-1 and GFAP immunoreactivity significantly augmented in the frontal cortex demonstrating microglial activation. Serum biomarkers of injury, NSE, TNF-alpha and leptin, were also elevated. Conclusion OBI triggers both inflammation and oxidative injury in the brain. This data in conjunction with our previous observations suggests that OBI triggers a cascade of events beginning with impaired cerebral vascular function leading to ischemia and chronic neurological consequences.

Original languageEnglish
Pages (from-to)14-22
Number of pages9
JournalBehavioural Brain Research
Volume340
DOIs
StatePublished - 15 Mar 2018
Externally publishedYes

Keywords

  • Brain
  • Edema
  • GFAP
  • Iba1
  • Lung
  • NFKB
  • NGF
  • NSE
  • Overpressure blast injury
  • Trauma

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