Cognitive dysfunction and hippocampal damage induced by hypoxic-ischemic brain injury and prolonged febrile convulsions in immature rats.
신생 흰쥐에서 저산소 허혈 뇌손상 및 지속적 열성 경련에 의한 인지기능 장애 및 해마 손상
- 주제(키워드) Hypoxic-ischemic encephalopathy , Febrile seizure , Epilepsy , Hippocampal injury
- 발행기관 고려대학교 대학원
- 지도교수 은백린
- 발행년도 2013
- 학위수여년월 2013. 2
- 학위구분 박사
- 학과 일반대학원 의학과
- 세부전공 소아청소년과학전공
- 원문페이지 41 p
- 실제URI http://www.dcollection.net/handler/korea/000000038846
- 본문언어 영어
- 제출원본 000045743215
초록/요약
Rationale: Perinatal hypoxic ischemic encephalopathy (HIE) and prolonged febrile seizures (FS) are common neurologic problems that occur during childhood. Clinical studies suggest that prolonged febrile seizures in children can induce hippocampal injury and later mesial temporal lobe epilepsy (MTLE). However, there is insufficient evidence from experimental studies to conclude that FS directly induces hippocampal injury. I studied cognitive function and histological changes and investigated which of the following is most detrimental to a child’s health: HIE, FS, or a dual pathologic effect. Methods: A rat model of HIE was created by completely severing the right common carotid artery, followed by inducing hypoxia (8% oxygen) at postnatal day (PD) 7. A FS model was induced by a heated stream of air and controlled for seizures over 20 minutes at PD10. Behavioral and cognitive functions were investigated by weekly open field tests from postnatal week (PW) 3 to PW7 and by daily testing using the Morris water maze test at PW8. Pathological changes in the hippocampus were observed in the control, HIE, FS, and HIE+FS groups. Results: The HIE group was prone to seizures induced by hyperthermia. The HIE+FS and FS groups showed mild anxiety behavior in the open field test. The Morris water maze test revealed a decline in cognitive function in the HIE+FS and HIE groups compared to the FS and control groups. Additionally, the HIE+FS and HIE groups showed significant hippocampal neuronal damage, astrogliosis, and volume loss, especially in the hippocampus, after maturation. FS alone induced minimal hippocampal neuronal damage without astrogliosis or volume loss. Conclusions: HIE can cause greater injury than prolonged FS, and FS alone causes minimal hippocampal neuronal damage in the immature brain.
more목차
Abstract i
Introduction 1
Materials and Methods 4
1. Animal models 4
2. Behavioral tests 6
3. Neurohistopathologic analyses 8
4. Statistical analysis 9
Results 10
1. Seizure latency and seizure threshold 10
2. Exploratory behavior 10
3. Spatial learning and reference memory 11
4. Immunohistochemistry 12
Discussion 14
References 18
Figures 23
Summary 34
