Hale Z Toklu1, Zhihui Yang2, Sehkar Oktay3, Yasemin Sakarya4, Nataliya Kirichenko4, Michael K Matheny5, Judy Muller-Delp6, Kevin Strang2, Philip J Scarpace5, Kevin K W Wang2, Nihal Tümer7. 1. Geriatric Research Education & Clinical Center, Malcom Randall Veterans Affairs Medical Center, FL, USA; University of Florida College of Medicine, Department of Pharmacology & Therapeutics, FL, USA. Electronic address: haletoklu@yahoo.com. 2. Center for Neuroproteomics & Biomarker Research, McKnight Brain Institute and Department of Psychiatry & Neuroscience, University of Florida College of Medicine, FL, USA. 3. University of Florida College of Medicine, Department of Pharmacology & Therapeutics, FL, USA; Marmara University School of Dentistry, Department of Biochemistry, Istanbul, Turkey. 4. Geriatric Research Education & Clinical Center, Malcom Randall Veterans Affairs Medical Center, FL, USA; University of Florida College of Medicine, Department of Pharmacology & Therapeutics, FL, USA. 5. University of Florida College of Medicine, Department of Pharmacology & Therapeutics, FL, USA. 6. Florida State University, College of Medicine Department of Biomedical Sciences, FL, USA. 7. Geriatric Research Education & Clinical Center, Malcom Randall Veterans Affairs Medical Center, FL, USA; University of Florida College of Medicine, Department of Pharmacology & Therapeutics, FL, USA. Electronic address: ntumer@ufl.edu.
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 30psi peak pressure, 2-2.5ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24h 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.
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 30psi peak pressure, 2-2.5ms), (3) Repeated OBI (r-OBI) (three exposures over one-week period). Lung and brain (cortex and cerebellum) tissues were collected at 24h 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.
Authors: Natalie N Nawarawong; Megan Slaker; Matt Muelbl; Alok S Shah; Rachel Chiariello; Lindsay D Nelson; Matthew D Budde; Brian D Stemper; Christopher M Olsen Journal: Eur J Neurosci Date: 2018-12-14 Impact factor: 3.386
Authors: Matthew J Muelbl; Megan L Slaker; Alok S Shah; Natalie N Nawarawong; Clayton H Gerndt; Matthew D Budde; Brian D Stemper; Christopher M Olsen Journal: Sci Rep Date: 2018-07-02 Impact factor: 4.379