Changes of biological reducing activity in rat brain following closed head injury: a cyclic voltammetry study in normal and heat-acclimated rats.
Reactive oxygen species (ROS) are normally generated in the brain during metabolism, and their production is enhanced by various insults. Low molecular weight antioxidants (LMWA) are one of the defense mechanisms of the living cell against ROS. The reducing capacity of brain tissue (total LMWA) was measured by cyclic voltammetry (CV), which records biological oxidation potential specific to the type of scavenger(s) present and anodic current intensity (Ia), which depends on scavenger concentration. In the present study, the reducing capacity of rat brain following closed head injury (CHI) was measured. In addition, CV of heat-acclimated traumatized rats was used to correlate endogenous cerebroprotection after CHI with LMWA activity. Sham-injured rat brains displayed two anodic potentials: at 350 +/- 50 mV (Ia = 0.75 +/- 0.06 microA/mg protein) and at 750 +/- 50 mV (Ia = 1.00 +/- 0.05 microA/mg protein). Following CHI, the anodic waves appeared at the same potentials as in the sham animals. However, within 5 min of CHI, the total reducing capacity was transiently decreased by 40% (p < 0.01). A second dip was detected at 24 h (60%, p < 0.005). By 48 h and at 7 days, the Ia levels normalized. The acclimated rats displayed anodic potentials identical to those of normothermic rats. However, the Ia of both potentials was lower (60% of control, p < 0.001). The Ia profile after CHI was the direct opposite of the normothermic Ia profile: no immediate decrease of Ia and an increase from 4 h and up to 7 days (40-50%, p < 0.001). We suggest that the lowered levels of LMWA in the post-CHI period reflect their consumption due to overproduction of free radicals. The augmented concentration of LMWA found in the brain of the heat-acclimated rats suggests that these rats are better able to cope with these harmful radicals, resulting in a more favorable outcome following CHI.
Beit-Yannai
E
E
Department of Pharmacology, Hebrew University School of Pharmacy, Jerusalem, Israel.
Kohen
R
R
Horowitz
M
M
Trembovler
V
V
Shohami
E
E
D000064:Acclimatization / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D001930:Brain Injuries / Q000378:metabolism* / Q000503:physiopathology; D006259:Craniocerebral Trauma / Q000378:metabolism; D004198:Disease Susceptibility; D004553:Electric Conductivity; D016166:Free Radical Scavengers; D006321:Heart / Q000503:physiopathology; D006358:Hot Temperature; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014364:Tryptophan / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014364:Tryptophan; D001205:Ascorbic Acid