title: Impact of hyperthermia before and during ischemia-reperfusion on neuronal damage and gliosis in the gerbil hippocampus induced by transient cerebral ischemia.
abstract: Hyperthermia can exacerbate the brain damage produced by ischemia. In the present study, we investigated the effects of hyperthermia before and during ischemia-reperfusion on neuronal damage and glial changes in the gerbil hippocampus following transient cerebral ischemia using cresyl violet staining, NeuN immunohistochemistry and Fluoro-Jade B histofluorescence staining. The animals were randomly assigned to 4 groups: (1) sham-operated animals with normothermia (normothermia + sham group); (2) ischemia-operated animals with normothermia (normothermia + ischemia group); (3) sham-operated animals with hyperthermia (hyperthermia + sham group); and (4) ischemia-operated animals with hyperthermia (hyperthermia + ischemia group). Hyperthermia (39.5 ± 0.2°C) was induced by exposing the gerbils to a heating pad connected to a rectal thermistor for 30 min before and during ischemia-reperfusion. In the normothermia+ischemia groups, a significant delayed neuronal death was observed in the stratum pyramidale (SP) of the hippocampal CA1 region (CA1) 5 days after ischemia-reperfusion. In the hyperthermia+ischemia groups, neuronal death in the SP of the CA1 occurred at 1 day post-ischemia, and neuronal death was observed in the SP of the CA2/3 region at 2 days post-ischemia. In addition, we examined activations of astrocytes and microglia using immunohistochemistry for anti-glial fibrillary acidic protein (GFAP) and anti-ionized calcium-binding adapter molecule 1 (Iba-1). GFAP-positive astrocytes and Iba-1-positive microglia in the ischemic hippocampus were activated much earlier and much more accelerated in the hyperthermia+ischemia groups than those in the normothermia+ischemia groups. Based on our findings, we suggest that an experimentally hyperthermic pre-condition before cerebral ischemic insult produces more extensive neuronal damage and glial activation in the ischemic hippocampus.
authors.affiliation: Department of Emergency Medicine, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea; Department of Emergency Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Min Joung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Emergency Medicine, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Jun Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Jeong-Hwi
authors.initials: JH
authors.lastname: Cho
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Joon Ha
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea.
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Ahn
authors.affiliation: Department of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, South Korea.
authors.forename: Hyun-Jin
authors.initials: HJ
authors.lastname: Tae
authors.affiliation: Department of Neuroscience, College of Medicine, Korea University, Seoul 136-705, South Korea.
authors.forename: Geum-Sil
authors.initials: GS
authors.lastname: Cho
authors.affiliation: Institute of Integrative Traditional & Western Medicine, Medical College, Yangzhou University, Yangzhou 225001, China.
authors.forename: Bing Chun
authors.initials: BC
authors.lastname: Yan
authors.affiliation: Department of Anatomy and Cell Biology, College of Veterinary Medicine, Seoul National University, Seoul 151-742, South Korea.
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan 330-714, South Korea.
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chunchen 200-702, South Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Bae
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Electronic address: mhwon@kangwon.ac.kr.
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
authors.affiliation: Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 200-701, South Korea. Electronic address: anajclee@kangwon.ac.kr.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000818:Animals; D016923:Cell Death; D004195:Disease Models, Animal; D005334:Fever / Q000150:complications / Q000473:pathology*; D005849:Gerbillinae; D005911:Gliosis / Q000209:etiology / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D002546:Ischemic Attack, Transient / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D017966:Pyramidal Cells / Q000473:pathology*; D011897:Random Allocation; D015427:Reperfusion Injury / Q000139:chemically induced / Q000473:pathology*
keywords: Delayed neuronal death; Glial cells; Hippocampal subregions; Hyperthermic pre-condition; Ischemia–reperfusion; Pyramidal neurons