전뇌성 허혈 뇌졸증 모델에서 신경세포 ROS에 의하여 유도된 MIP-1α 의 발현이 마이크로글리아 활성 기작에 미치는 영향에 대한 연구
Essential role of ROS-mediated MIP-1α expression for microglial activation following global forebrain ischemia in rat
- 주제(키워드) Ischemia , Hippocampus , Microglia , ROS , MIP-1α , Ferric iron
- 발행기관 아주대학교
- 지도교수 곽병주, 이용범
- 발행년도 2006
- 학위수여년월 2006. 2
- 학위명 석사
- 학과 및 전공 일반대학원 신경과학기술과정
- 본문언어 한국어
초록/요약
Microglia play an essential role in inflammation and neuronal death following hypoxic-ischemic brain injury. Here, we present that activation of microglia in the CA1 layer of the hippocampus following global forebrain ischemia is induced by ROS-mediated chemokine expression in the CA1 neuron. Activation of OX42-positive microglia was detected in the CA1 layer of the hippocampus within 24 h after global forebrain ischemia and peaked at 72 h. Macrophage inflammatory protein-1a (MIP-1α) was localized mainly in cell body and dendrites of the CA1 pyramidal neurons and markedly increased within 2 d in the CA1 neuron. Administration of trolox, a vitamin E analogue, prevented MIP-1a expression and microglial activation as well as ROS production in the CA1 region of the hippocampus. In addition, microglial activation was prevented by the intracerebroventricular administration of vMIP-2, a MIP-1α receptor antagonist. This implies that ROS-mediated MIP-1α expression mediates microglial activation after ischemia. In support of this, the intrahippocampal injection of FeCl2 induced ROS production, MIP-1α expression and microglial activation. The present study provides evidence that neuronal ROS produced following transient forebrain ischemia causes activation of microglia presumably through the MIP-1α expression.
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TABLE OF CONTENTS
APPROVAL PAGE i
ACKNOLEDGEMENT ii
ABSTRACT iii
TABLE OF CONTENTS v
LIST OF FIGURES vii
LIST OF ABBREVIATION viii
I. INTRODUCTION 1
II. MATERIALS AND METHODS 3
A. Chemicals 3
B. Global forebrain ischemia 3
C. Hippocampal neuron culture 4
D. Tissue preparation 4
E. Immunofluorescence staining 5
F. Detection of ROS 6
G. Reverse transcription-polymerase chain reaction (RT-PCR) 7
H. Western blotting anlysis. 8
I. Counting of hippocampal CA1 microglial cells 8
J. Statistical analysis 9
III. RESULTS 10
A. Microglial activation is selectively occurred in the CA1
region following global forebrain ischemia. 10
B. Microglial activation is correlated with neuronal ROS
production following global forebrain ischemia.. 10
C. Ferric iron injection into the intra-hippocampal area induces the neuronal ROS production and activation of microglia in the hippocampus 11
D. Ferric iron treatment induces the expression of MIP-1a in the hippocampal neuron culture. 12
E. In vivo MIP-1a expression was increased in the CA1 pyramidal neuron following global forebrain ischemia. 13
F.MIP-1α receptor antagonist (vMIP-2) prevents activation of
microglia following global forebrain ischemia 14
IV. DISCUSSION 29
REFERENCES 34
국문요약 38
