2001 Fiscal Year Final Research Report Summary
Basic investigation of hypothermia for a treatment of stroke : ischemic neuronal damage by the disruption of blood-brain barrier and microglial activation
| Project/Area Number |
12557131
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Ehime University |
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Principal Investigator |
OHNISHI Katsuyuki Ehime University, Faculty of Medicine, Assistant Professor, 医学部・附属病院, 講師 (90127887)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Youichi Kanazawa University, School of Pharmacy, Associate Professor, 薬学部, 助教授 (90180413)
FUKUHARA Toshiyuki Ehime University, Faculty of Medicine, Instructor, 医学部, 助手 (00228925)
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| Project Period (FY) |
2000 – 2001
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| Keywords | hypothermia / blood brain barrier / brain ischemia / microglia / albumin / theanine |
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| Research Abstract |
Blood-brain barrier (BBB) breakdown was evaluated by examining extravasation of intravenously injected Evans Blue dye in forebrain ischemic gerbils. Dye extravasation was estimated by the fluorometric method. Slight extravasation was observed in the forebrain 1 days after ischemia, and was most severe 4 days after ischemia. Extravasation decreased in whole of brain in the hypothermic gerbils. When serum were administered through the lateral ventricle after forebrain ischemia under hypothermic conditions, neuronal death was detected in CA1 neurons of the hippocampus. Infarction volume 24 h after 1 h MCA occlusion decreased in none-albumin rats compared with normal rats. These results suggest that infiltration of serum factors into brain parenchyma may play a key role in ischemic neuronal death.
We examined the effect of serum on the production of super oxide (O_2^-), nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in rat cultured microglia. We found that a serum factor, albumin, in
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creased phorbol ester (PMA)-induced O_2^- production and that serum also enhanced lipopolysaccharide (LPS)-induced production of NO and TNF-α. We identified the active site of this enhancement within the albumin molecule. The activated of a series of synthesized peptides conclusely indicated that the minimum active sequences was Leu-His-Thr-Leu. Activated microglia can release various neurotoxic mediators. Such neurotoxic mediators have been proposed to exert neuronal damage under brain ischemia. Therefore, suppression of microglial activation will open a new window for treatment of ischemic stroke.
We examined the protective effect of short-duration and mild hypothermia in combination with daily γ-glutamylethylamide (theanine) treatment on delayed neuronal death in transient forebrain ischemia of gerbils. Theanine was administered daily 5 mg/kg alter ischemia for 30 days. After survival of 30 days, the extent of CA1 neuronal damage in the hippocampus was assessed histologically. Short-duration and mild postischemic hypothermia combined with theanine treatment led to significant increase (67% and 72%, respectively) in viable CA1 neurons, compared to the control group (8% survival). These findings indicate that short-duration and mild hypothermia in combination with theanine has a beneficial effect on ischemic neuronal damage consistently. Less
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Research Products
(18 results)
