Detection of free radical activity during transient global ischemia and recirculation: Effects of intraischemic brain temperature modulation

M. Y T Globus, R. Busto, B. Lin, H. Schnippering, Myron Ginsberg

Research output: Contribution to journalArticle

329 Citations (Scopus)

Abstract

To obtain direct evidence of oxygen radical activity in the course of cerebral ischemia under different intraischemic temperatures, we used a method based on the chemical trapping of hydroxyl radical in the form of the stable adducts 2,3- and 2,5-dihydroxybenzoic acid (DHBA) following salicylate administration. Wistar rats were subjected to 20 min of global forebrain ischemia by two-vessel occlusion plus systemic hypotension (50 mm Hg). Intraischemic striatal temperature was maintained as normothermic (37°C), hypothermic (30°C), or hyperthermic (39°C) but was held at 37°C before and following ischemia. Salicylate was administered either systemically (200 mg/kg, i.p.) or by continuous infusion (5 mM) through a microdialysis probe implanted in the striatum. Striatal extracellular fluid was sampled at regular intervals before, during, and after ischemia, and levels of 2,3- and 2,5-DHBA were assayed by HPLC with electrochemical detection. Following systemic administration of salicylate, stable baseline levels of 2,3- and 2,5-DHBA were observed before ischemia. During 20 min of normothermic ischemia, a 50% reduction in mean levels of both DHBAs was documented, suggesting a baseline level of hydroxyl radical that was diminished during ischemia, presumably owing to oxygen restriction to tissue at that time. During recirculation, 2,3- and 2,5-DHBA levels increased by 2.5-and 2.8- fold, respectively. Levels of 2,3-DHBA remained elevated during 1 h of reperfusion, whereas the increase in 2,5-DHBA levels persisted for 2 h. The increases in 2,3- and 2,5-DHBA levels observed following hyperthermic ischemia were significantly higher (3,8- and fivefold, respectively). In contrast, no significant changes in DHBA levels were observed following hypothermic ischemia. The postischemic changes in DHBA content observed following local administration of salicylate were comparable to the results obtained with systemic administration, thus confirming that the hydroxyl radicals arose within brain parenchyma itself. These results provide evidence that hydroxyl radical levels are increased during postischemic recirculation, and this process is modulated by intraischemic brain temperature. Hence, these data suggest a possible mechanism for the effects of temperature on ischemic outcome and support a key role for free radical-induced injury in the development of ischemic damage.

Original languageEnglish
Pages (from-to)1250-1256
Number of pages7
JournalJournal of Neurochemistry
Volume65
Issue number3
StatePublished - Jan 1 1995

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Salicylates
Free Radicals
Brain
Ischemia
Hydroxyl Radical
Modulation
Temperature
Corpus Striatum
Acids
Rats
Reactive Oxygen Species
alpha-resorcylic acid
Tissue
Extracellular Fluid
Oxygen
Microdialysis
Prosencephalon
Brain Ischemia
Fluids
Hypotension

Keywords

  • Cerebral ischemia
  • Hydroxyl radicals
  • Microdialysis
  • Temperature

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Detection of free radical activity during transient global ischemia and recirculation : Effects of intraischemic brain temperature modulation. / Globus, M. Y T; Busto, R.; Lin, B.; Schnippering, H.; Ginsberg, Myron.

In: Journal of Neurochemistry, Vol. 65, No. 3, 01.01.1995, p. 1250-1256.

Research output: Contribution to journalArticle

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