2005 Fiscal Year Final Research Report Summary
Effects of inflammatory response on outcome after severe forebrain ischemia in the rat.
| Project/Area Number |
16591524
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Health Sciences University of Hokkaido (2005)
Yamagata University (2004) |
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Principal Investigator |
MIURA Yoshihide Health Sciences University of Hokkaido, School of dentistry, Professor, 歯学部, 教授 (50241716)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAI Michiko Yamagata University, School of medicine, instructor, 医学部, 助手 (20143092)
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| Project Period (FY) |
2004 – 2005
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| Keywords | rat / forebrain ischemia / propofol / isoflurane / cytokine / inflammation |
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| Research Abstract |
We investigated the effects of propofol or isoflurane anesthesia on the brain inflammatory cytokine mRNA expressions after severe forebrain ischemia in the rat. Brain parenchymal expressions of TNF-alfa, IL-1beta, and IL-6 mRNAs were sequentially measured using RT-PCR. EEG burst suppression ratio (BSR) ranging from 3 - 9 was used for the index of equi-potentcy for the anesthetic depth.
Ischemia protocol
Fasted Male Sprague-Dawley rats, 〜300g of body weight, were used. Anesthesia was induced with isoflurane. Rats were intubated and mechanically ventilated to have normtension and normocapnea. Pericranial temperature was servoregultated at 37℃ throughout the experiment. Rats were randomly allocated either propofol or isoflurane anesthesia. After surgery, anesthetic depth at predefined BSR were maintained for 30 min, then 10 min severe forebrain ischemic insults were given. Rats were sacrificed at 0, 4, 16, 24, 48, 72, and 144 h after ischemia and the brain was immediately extracted.
Measurem
… More
ent of brain parenchymal cytokine mRNAs
Brains were cut at Bregma -4 mm for 1 mm thick, and put in lysis buffer containing magnetic beads, then the tube was homogenized and centrifuged. The supernatant was processed with MagNA Pure LC system to purify mRNA. Relative cytokine mRNAs expressions were quantitatively assayed using LightCycler instrument (RT-PCR).
Results
TNF-alfa : Peak mRNA expressions were observed at 4 h in both groups. In propofol group, the expression was rapidly diminished, however, the expression was prolonged in isoflurane group. IL-1beta : In propofol group, the mRNA expression was extremely inhibited throughout, however, in isoflurane group, approximately 20 times higher expression from 4 -24 h were observed. IL-6 : In isoflurane group, the mRNA expression was observed from 0 to 16 h post-ischemia. In propofol group, the expression was observed from 4 to 24 h, however, the magnitude was 25 - 50% lower compared to isoflurane group.
Conclusion
Anesthesitcs affected the pattern of brain parenchymal cytokine mRNA expressions after severe forebrain ischemia. It was suggested that inflammatory response was more suppressed with propofol than isoflurane. Less
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