| Project/Area Number |
12470215
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Embryonic/Neonatal medicine
|
|---|
| Research Institution | Kobe University |
|---|
Principal Investigator |
NAKAMURA Hajime Graduate School of Medicine, Kobe University, Professor, 大学院・医学系研究科, 教授 (40030978)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TSUNEISHI Syuichi University Hospital, Kobe University, Assistant Professor, 医学部・附属病院, 助手 (10271040)
YONETANI Masahiko University Hospital, Kobe University, Lecturer, 医学部・附属病院, 講師 (60221678)
TAKADA Satoshi Faculty of Health Science, Kobe University, Professor, 医学部, 教授 (10216658)
YOKOYAMA Naoki University Hospital, Kobe University, Assistant Professor, 医学部・附属病院, 助手 (20314487)
|
|---|
| Project Period (FY) |
2000 – 2001
|
| Project Status |
Completed (Fiscal Year 2001)
|
| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2001: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2000: ¥10,600,000 (Direct Cost: ¥10,600,000)
|
|---|
| Keywords | hypoxic-ischemic encephalopathy / brain hypothermia / apoptosis / caspase-3 / BAF / free radicals / microdialysis / hydroxyl radical / 新生児 |
|---|
| Research Abstract |
The aim of this study is to determine the efficacy of brain hypothermia against neonatal hypoxic-ischemic (HI) brain damage.
1. Systemic hypothermia and caspase inhibitor protect hippocampal neuron against HI insult in developing rat. Using P7 rat HI model induced by ligation of left carotid artery and exposure to 8% O_2 for 1h, we demonstrated that systemic hypothermia (30℃) and pan-caspase inhibitor, BAF, could inhibit activation of caspase-3 and lessen neuronal cell loss in ipsilateral hippocampus. Systemic hypothermia inhibited the Hi-induced increase of caspase-3 activity to about half of normothrmia group, and combination with BAF resulted in no increase of caspase-3 activity anymore.
The loss of hippocampal neuronal cells at 7d after HI significantly reduced to 5% by combination of systemic hypothermia and BAF in contrast to 37% of normothermia group.
2. Selective brain hypothermia reduces hydroxyl radical production during HI and reperfusion in developing rat. Using P7 HI (90min) and reperfusion model, we demonstrated that selective brain hypothermia (30-32℃) could reduce the Hi-induced increase in hydroxyl radical significantly. Selective hypothermia remarkably reduced the number of both necrotic and apoptotic cells in ipsilateral hippocampus, striatum and cortex.
These results indicate that brain hypothermia reduces the activation of caspase-3 and production of hydroxyl radical induced by HI insult and reperfusion, which may have protective effects against necrotic and apoptotic neuronal cell damage in the developing brain.
|
