title: Overpressure blast-wave induced brain injury elevates oxidative stress in the hypothalamus and catecholamine biosynthesis in the rat adrenal medulla.
abstract: Explosive overpressure brain injury (OBI) impacts the lives of both military and civilian population. We hypothesize that a single exposure to OBI results in increased hypothalamic expression of oxidative stress and activation of the sympatho-adrenal medullary axis. Since a key component of blast-induced organ injury is the primary overpressure wave, we assessed selective biochemical markers of autonomic function and oxidative stress in male Sprague Dawley rats subjected to head-directed overpressure insult. Rats were subjected to single head-directed OBI with a 358kPa peak overpressure at the target. Control rats were exposed to just noise signal being placed at ~2m distance from the shock tube nozzle. Sympathetic nervous system activation of the adrenal medullae (AM) was evaluated at 6h following blast injury by assessing the expression of catecholamine biosynthesizing enzymes, tyrosine hydroxylase (TH), dopamine-β hydroxylase (DβH), neuropeptide Y (NPY) along with plasma norepinephrine (NE). TH, DβH and NPY expression increased 20%, 25%, and 91% respectively, following OBI (P<0.05). Plasma NE was also significantly elevated by 23% (P<0.05) following OBI. OBI significantly elevated TH (49%, P<0.05) in the nucleus tractus solitarius (NTS) of the brain stem while AT1 receptor expression and NADPH oxidase activity, a marker of oxidative stress, was elevated in the hypothalamus following OBI. Collectively, the increased levels of TH, DβH and NPY expression in the rat AM, elevated TH in NTS along with increased plasma NE suggest that single OBI exposure results in increased sympathoexcitation. The mechanism may involve the elevated AT1 receptor expression and NADPH oxidase levels in the hypothalamus. Taken together, such effects may be important factors contributing to pathology of brain injury and autonomic dysfunction associated with the clinical profile of patients following OBI.
authors.affiliation: Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608, USA. ntumer@ufl.edu
authors.forename: Nihal
authors.initials: N
authors.lastname: Tümer
authors.forename: Stanislav
authors.initials: S
authors.lastname: Svetlov
authors.forename: Melissa
authors.initials: M
authors.lastname: Whidden
authors.forename: Nataliya
authors.initials: N
authors.lastname: Kirichenko
authors.forename: Victor
authors.initials: V
authors.lastname: Prima
authors.forename: Benedek
authors.initials: B
authors.lastname: Erdos
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sherman
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
authors.forename: Robert
authors.initials: R
authors.lastname: Yezierski
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Scarpace
authors.forename: Charles
authors.initials: C
authors.lastname: Vierck
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
mesh_terms: D000313:Adrenal Medulla / Q000293:injuries* / Q000378:metabolism*; D000818:Animals; D001753:Blast Injuries / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis*; D007031:Hypothalamus / Q000293:injuries* / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D002395:Catecholamines; D017382:Reactive Oxygen Species