2002 Fiscal Year Final Research Report Summary
Mechanism for effects of hypothemic therapy on traumatic brain injury and Development of its ultimate procedure
Project/Area Number |
12671477
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Anesthesiology/Resuscitation studies
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Research Institution | Ehime University (2001-2002) Kagawa Medical School (2000) |
Principal Investigator |
AIBIKI Mayuki Ehime University, Faculty of Medicine Associate Professor, 医学部, 助教授 (70148162)
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Co-Investigator(Kenkyū-buntansha) |
MAEKAWA Souichi Ehime University, Faculty of Medicine Instructor, 医学部, 助手 (50284419)
SEKI Keisuke Kagawa Med Univ Hosp, Lecturer, 医学部附属病院, 講師 (20226632)
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Project Period (FY) |
2000 – 2002
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Keywords | Hypothermic Therapy / Cerebral Microglia / Cytokines / Nitric Oxide / Temperature Change |
Research Abstract |
Therapeutic moderate hypothermia has the potential for neuronal protection against brain injury. Microglia, a type of immune-related cell in the brain, may play a certain role in neuronal damage subsequent to injury. We examined the effects of culture temperature changes from 37 to 33 or 30。C on mediator release, including nitric oxide (NO), IL-6 and TNF-a from, LPS-stimulated microglia harvested from neonatal rats. The production of NO was measured by a nitrite accumulation method in a culture medium ; while cytokines, IL-6 and TNF-a were measured by ELISA At 30 and 33。C, NO production stimulated by LPS decreased to 10 and 30% of the control (37。C) respectively 24 hours after the stimulation, and the decrease was sustained for 48 hours. IL-6 production at 30 and 33。C was also reduced to 30% of the control from 6 hours after the activation. Such responses lasted throughout the study. However, TNF-a release at 30 and 33。C was depressed for only 6 hours after stimulation, followed by subsequent elevation to levels similar to those at 37。C. Microglial morphological activation, showing changes from round to bipolar, reached a peak at 6 hours in the 37。C group, returning to round 12 hours after LPS application. In 30 and 33。C, the zenith was detected at 6 hours, activation remaining even 12 hours after the stimulation, suggesting the prolongation of the microglial response to LPS, which was inconsistent with changes in TNF release. The present study indicates that 1) decreasing culture temperature inhibits the production of NO and IL-6 from activated microglia, 2) differences were found in the degree or time course change between TNF-a and the other mediators, 3) the time course of morphological changes in microglia was dependent on culture temperature. Further studies are required to define the mechanisms for such differences in mediator release from cooled microglia and also to clarify the inconsistency between morphological change and its function in the cell.
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Research Products
(2 results)