Effect of intra-ischemic hypothermia on the expression of c-Fos and c-Jun, and DNA binding activity of AP-1 after focal cerebral ischemia in rat brain

Kazunori Akaji, Sadao Suga, Tadahiro Fujino, Keita Mayanagi, Joji Inamasu, Takashi Horiguchi, Shuzo Sato, Takeshi Kawase

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

It is unknown whether immediate early gene (IEG) induction and subsequent late gene regulation after ischemia is beneficial or deleterious. The aim of this study was to examine the effect of hypothermia on expression of c-Fos and c-Jun, and AP-1 DNA binding activity, after transient focal cerebral ischemia in rat brain, and clarify the role of IEGs and AP-1 after insults. Male Wistar rats underwent right middle cerebral artery occlusion for 1 h with the intraluminal suture method. During ischemia, animals were assigned to either normothermic (NT) or hypothermic (HT) groups. In the NT group, brain temperature was observed to spontaneously increase to 40°C during ischemia. In the HT group, brain temperature decreased to 30°C. Infarct volume in cortex was decreased in the HT group, compared with that in the NT group (P<0.001). Increased c-Fos immunoreactivity in the cortex was observed at 3 h after reperfusion in the HT, but not the NT group, while c-Jun expression was not affected by HT treatment. There was also a significant increase in AP-1 DNA binding activity at 3 h in the HT group when compared to the NT group (P<0.01). In conclusion, hypothermia decreased cerebral infarction in association with early increases in c-Fos expression and AP-1 DNA binding activity in peri-infarct cortex. It remains to be established whether such responses are a cause or consequence of cell survival, but these results clearly establish that altered transcription is a key feature of tissue spared following hypothermic focal ischemia.

Original languageEnglish
Pages (from-to)149-157
Number of pages9
JournalBrain Research
Volume975
Issue number1-2
DOIs
Publication statusPublished - 2003 Jun 13

Fingerprint

Transcription Factor AP-1
Hypothermia
Brain Ischemia
Ischemia
DNA
Brain
Temperature
Immediate-Early Genes
Middle Cerebral Artery Infarction
Transient Ischemic Attack
Cerebral Infarction
Sutures
Reperfusion
Wistar Rats
Cell Survival
Genes

Keywords

  • AP-1
  • c-Fos
  • c-Jun
  • Focal cerebral ischemia
  • Hypothermia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Effect of intra-ischemic hypothermia on the expression of c-Fos and c-Jun, and DNA binding activity of AP-1 after focal cerebral ischemia in rat brain. / Akaji, Kazunori; Suga, Sadao; Fujino, Tadahiro; Mayanagi, Keita; Inamasu, Joji; Horiguchi, Takashi; Sato, Shuzo; Kawase, Takeshi.

In: Brain Research, Vol. 975, No. 1-2, 13.06.2003, p. 149-157.

Research output: Contribution to journalArticle

Akaji, Kazunori ; Suga, Sadao ; Fujino, Tadahiro ; Mayanagi, Keita ; Inamasu, Joji ; Horiguchi, Takashi ; Sato, Shuzo ; Kawase, Takeshi. / Effect of intra-ischemic hypothermia on the expression of c-Fos and c-Jun, and DNA binding activity of AP-1 after focal cerebral ischemia in rat brain. In: Brain Research. 2003 ; Vol. 975, No. 1-2. pp. 149-157.
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AU - Fujino, Tadahiro

AU - Mayanagi, Keita

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AU - Horiguchi, Takashi

AU - Sato, Shuzo

AU - Kawase, Takeshi

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N2 - It is unknown whether immediate early gene (IEG) induction and subsequent late gene regulation after ischemia is beneficial or deleterious. The aim of this study was to examine the effect of hypothermia on expression of c-Fos and c-Jun, and AP-1 DNA binding activity, after transient focal cerebral ischemia in rat brain, and clarify the role of IEGs and AP-1 after insults. Male Wistar rats underwent right middle cerebral artery occlusion for 1 h with the intraluminal suture method. During ischemia, animals were assigned to either normothermic (NT) or hypothermic (HT) groups. In the NT group, brain temperature was observed to spontaneously increase to 40°C during ischemia. In the HT group, brain temperature decreased to 30°C. Infarct volume in cortex was decreased in the HT group, compared with that in the NT group (P<0.001). Increased c-Fos immunoreactivity in the cortex was observed at 3 h after reperfusion in the HT, but not the NT group, while c-Jun expression was not affected by HT treatment. There was also a significant increase in AP-1 DNA binding activity at 3 h in the HT group when compared to the NT group (P<0.01). In conclusion, hypothermia decreased cerebral infarction in association with early increases in c-Fos expression and AP-1 DNA binding activity in peri-infarct cortex. It remains to be established whether such responses are a cause or consequence of cell survival, but these results clearly establish that altered transcription is a key feature of tissue spared following hypothermic focal ischemia.

AB - It is unknown whether immediate early gene (IEG) induction and subsequent late gene regulation after ischemia is beneficial or deleterious. The aim of this study was to examine the effect of hypothermia on expression of c-Fos and c-Jun, and AP-1 DNA binding activity, after transient focal cerebral ischemia in rat brain, and clarify the role of IEGs and AP-1 after insults. Male Wistar rats underwent right middle cerebral artery occlusion for 1 h with the intraluminal suture method. During ischemia, animals were assigned to either normothermic (NT) or hypothermic (HT) groups. In the NT group, brain temperature was observed to spontaneously increase to 40°C during ischemia. In the HT group, brain temperature decreased to 30°C. Infarct volume in cortex was decreased in the HT group, compared with that in the NT group (P<0.001). Increased c-Fos immunoreactivity in the cortex was observed at 3 h after reperfusion in the HT, but not the NT group, while c-Jun expression was not affected by HT treatment. There was also a significant increase in AP-1 DNA binding activity at 3 h in the HT group when compared to the NT group (P<0.01). In conclusion, hypothermia decreased cerebral infarction in association with early increases in c-Fos expression and AP-1 DNA binding activity in peri-infarct cortex. It remains to be established whether such responses are a cause or consequence of cell survival, but these results clearly establish that altered transcription is a key feature of tissue spared following hypothermic focal ischemia.

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