Cognitive Dysfunction and Hippocampal Damage Induced by Hypoxic-Ischemic Brain Injury and Prolonged Febrile Convulsions in Immature Rats.
OBJECTIVE
Perinatal hypoxic-ischemic encephalopathy (HIE) and prolonged febrile seizures (pFS) are common neurologic problems that occur during childhood. However, there is insufficient evidence from experimental studies to conclude that pFS directly induces hippocampal injury. We studied cognitive function and histological changes in a rat model and investigated which among pFS, HIE, or a dual pathologic effect is most detrimental to the health of children.


METHODS
A rat model of HIE at postnatal day (PD) 7 and a pFS model at PD10 were used. Behavioral and cognitive functions were investigated by means of weekly open field tests from postnatal week (PW) 3 to PW7, and by daily testing with the Morris water maze test at PW8. Pathological changes in the hippocampus were observed in the control, pFS, HIE, and HIE+pFS groups at PW9.


RESULTS
The HIE priming group showed a seizure-prone state. The Morris water maze test revealed a decline in cognitive function in the HIE and HIE+pFS groups compared with the pFS and control groups. Additionally, the HIE and HIE+pFS groups showed significant hippocampal neuronal damage, astrogliosis, and volume loss, after maturation. The pFS alone induced minimal hippocampal neuronal damage without astrogliosis or volume loss.


CONCLUSIONS
Our findings suggest that pFS alone causes no considerable memory or behavioral impairment, or cellular change. In contrast, HIE results in lasting memory impairment and neuronal damage, gliosis, and tissue loss. These findings may contribute to the understanding of the developing brain concerning conditions caused by HIE or pFS.
Department of Pediatrics, Korea University College of Medicine, Seoul, Korea.
Jung Hye
JH
Byeon
Department of Pediatrics, Korea University College of Medicine, Seoul, Korea.
Gun-Ha
GH
Kim
Department of Anatomy and Division of Brain Korea 21 Biomedical Science, Korea University College of Medicine, Seoul, Korea.
Joo Yeon
JY
Kim
Department of Anatomy and Division of Brain Korea 21 Biomedical Science, Korea University College of Medicine, Seoul, Korea.
Woong
W
Sun
Department of Anatomy and Division of Brain Korea 21 Biomedical Science, Korea University College of Medicine, Seoul, Korea.
Hyun
H
Kim
Department of Pediatrics, Korea University College of Medicine, Seoul, Korea.
Baik-Lin
BL
Eun
Epilepsy; Febrile seizure; Hippocampal injury; Hypoxic-ischemic encephalopathy