Title Page
Contents
I. INTRODUCTION 8
II. MATERIALS AND METHODS 10
1. Ethics Statement and Experimental Animals 10
2. Traumatic BI Surgery 10
3. Brain Sample Preparation 10
4. Evaluation of Hippocampal Neuronal Death 11
5. Evaluation of ASMase and Ceramide 11
6. Immunofluorescence Assay 12
7. Detection of Live Neurons 12
8. Behavior Test 13
9. Data Analysis 13
III. RESULTS 14
1. Imipramine Reduces Acid Sphingomyelinase and Ceramide Overexpression after Traumatic Brain Injury 14
2. Imipramine Reduces Traumatic Brain Injury-Induced Hippocampal Neuron Death 18
3. Imipramine Reduces Oxidative Damage and Dendritic Loss after Traumatic Brain Injury 20
4. Imipramine Reduces Traumatic Brain Injury-Induced Astrocyte and Microglia Activation. 22
5. Imipramine Reduced Traumatic Brain Injury-Induced Neuronal Death and Cognitive Impairment 24
IV. DISCUSSION 28
V. References 33
ABSTRACT KOREAN 40
ABSTRACT ENGLISH 42
Figure 1. Imipramine Reduces Acid Sphingomyelinase and Ceramide Overexpression after Traumatic Brain Injury. Imipramine treatment reduced ASMase and ceramide... 17
Figure 2. Imipramine treatment reduces hippocampal neuron death 24 h after TBI. (A,B) Representative fluorescence images showing degenerating neurons stained... 19
Figure 3. Imipramine treatment decreased lipid peroxidation and microtubule damage 24 h after TBI. (A) Immunofluorescence images showing lipid... 21
Figure 4. Imipramine treatment reduced glial activation 24 h after TBI. (A) Representative images showing astrocytes and microglia stained with GFAP (red) in... 23
Figure 5. Imipramine restored TBI-induced delayed neuronal loss, neurological deficits, and memory dysfunction. (A) Experimental procedures... 27
Figure 6. Hypothetical connections between imipramine and TBI-induced neuronal death. (A) TBI-induced neuronal death mechanism; (1) under TBI condition, excessive... 29