Postischemic hypothermia inhibits the generation of hydroxyl radical following transient forebrain ischemia in rats

Takashi Horiguchi, Katsuyoshi Shimizu, Masahiro Ogino, Sadao Suga, Joji Inamasu, Takeshi Kawase

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Abstract

A small reduction of body temperature during reperfusion following cerebral ischemia has been known to ameliorate neuronal injury. However, the mechanisms underlying postischemic hypothermia-induced neuroprotection are poorly understood. The burst of reactive oxygen species (ROS) formation that occurs during reperfusion has been documented to be involved in ischemic neuronal degeneration. In this study, we investigated the effect of postischemic hypothermia on ROS production following transient forebrain ischemia using an in vivo microdialysis technique. Forebrain ischemia was induced by bilateral carotid artery occlusion combined with hemorrhagic hypotension for 20 min in male Wistar rats. The body temperature was kept at 37°C during ischemia and controlled at either 32°C or 37°C after reperfusion. The amount of hydroxyl radical produced in striatum was evaluated by measurement of 2,3- and 2,5-dihydroxybenzoic acid (DHBA), which is generated by salicylate hydroxylation. We also measured the extracellular concentration of xanthine, while determining striatal blood flow by the hydrogen clearance technique. In animals whose postischemic body temperature was maintained at 37°C, the levels of 2,3- and 2,5-DHBA significantly increased after reperfusion. The peak levels of 2,3- and 2,5- DHBA were 2.9-fold and 2.7-fold increased above the corresponding baseline values, respectively. Postischemic hypothermia completely inhibited the hydroxyl radical formation. Likewise, xanthine formation was also inhibited by postischemic hypothermia. In contrast, striatal cerebral blood flow was not altered by temperature modulation during reperfusion. These results suggest that inhibition of ROS production accompanied with suppression of xanthine formation is implicated in the neuroprotection of postischemic hypothermia.

Original languageEnglish
Pages (from-to)511-520
Number of pages10
JournalJournal of Neurotrauma
Volume20
Issue number5
DOIs
Publication statusPublished - 2003 May 1

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Keywords

  • Delayed neuronal death
  • Free radical
  • Neuroprotection
  • Reperfusion
  • Temperature
  • Xanthine

ASJC Scopus subject areas

  • Clinical Neurology

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