Title Page

Contents

ABSTRACT ENGLISH 9

INTRODUCTION 11

MATERIAL AND METHODS 13

1. Ethics statement and care of experiment animal. 13

2. Seizure induction. 14

3. Amlodipine administration. 14

4. Brain sample preparation. 15

5. Detection of zinc accumulation. 15

6. Detection of oxidative stress in the hippocampal region. 16

7. Immunofluorescence assay. 17

8. Immunohistochemistry assay. 18

9. Behavioral test 19

9.1. Barnes maze test. 19

9.2. Adhesive removal test. 19

10. Data Analysis 20

RESULTS 20

1. Amlodipine administration reduced Cav 1.2 activation and zinc accumulation in neurons following seizure. 20

2. Administration of amlodipine decreased reactive oxidative stress (ROS) after seizure. 22

3. Amlodipine administration increased neuron survival after seizure. 22

4. Amlodipine reduced blood brain barrier breakdown after seizure. 23

5. Amlodipine administration reduced astrocyte over-activation after seizure. 24

6. Amlodipine administration reduced microglia over-activation after seizure. 25

7. Amlodipine administration reduced microtubule disruption after seizure. 25

8. Amlodipine administration improved spatial cognitive, memory and cognitive function recovery after seizure. 27

DISCUSSION 28

REFERENCES 47

ABSTRACT KOREAN 51

Figure 1. (A, C) Confocal micrographs of Cav1.2 (red), NeuN (green), and DAPI (blue) in the hippocampal CA1 and CA3 regions. Scale bar ＝ 20 ㎛. (B, D) The bar graph shows... 32

Figure 2. ROS was detected using 4-hydroxy-2-nonenal (4HNE) (red) staining in the hippocampal CA1, CA3, dentate gyrus (DG), and subiculum (Sub) regions, 7 days after the... 33

Figure 3. (A) Micrographs of NeuN (+) cells representing surviving cells in the hippocampal CA1, CA3, hilus, and subiculum (Sub) regions. The amount of surviving... 35

Figure 4. (A, B) The micrographs show the amount of IgG leakage in a specific region of the whole brain. There is a twofold difference in IgG leakage between the seizure-... 37

Figure 5. (A) The micrographs show the staining of GFAP (green), C3 (red), and DAPI (blue) in the hippocampal CA1 region. (B) The bar graph illustrates the intensity of GFAP, which... 39

Figure 6. (A) The micrographs depict the staining of Iba1 (red), CD68 (green), and DAPI (blue). There is a high presence of detected cells positive for both Iba1 and CD68 in the... 41

Figure 7. (A) The micrographs illustrate the staining of MAP2 (green) and DAPI (blue). The intensity of MAP2 staining in the seizure groups is lower compared to the sham groups.... 43

Figure 8. One week following the seizures for the seizure groups, and after a recovery period for the sham groups, we conducted several tests: (A) Barnes Maze Test: This test... 45