The effects of dantrolene on hypoxic-ischemic injury in the neonatal rat brain.

The effects of dantrolene on hypoxic-ischemic injury in the neonatal rat brain. Research Abstract Details 

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The effects of dantrolene on hypoxic-ischemic injury in the neonatal rat brain. Abstract Text:

Mijeung Gwak,Pyonghwan Park,Kisoo Kim,Keunho Lim,Sungmoon Jeong,Chongwha Baek,Jonghwan Lee,Mijeung Gwak,Pyonghwan Park,Kisoo Kim,Keunho Lim,Sungmoon Jeong,Chongwha Baek,Jonghwan Lee,

BACKGROUND: The pathophysiology of brain damage from hypoxia or ischemia has been ascribed to various mechanisms and cascades. Intracellular calcium overload and a calcium excitotoxic cascade have been implicated. It has been suggested that disturbances of endoplasmic reticulum calcium homeostasis are involved in the induction of neuronal cell injury. Two types of intracellular Ca(2+)-release channels, involving the ryanodyne receptor and the inositol (1,4,5)-triphosphate receptor, are essential for Ca(2+) signaling in cells. Dantrolene, which is used for the treatment of malignant hyperthermia syndrome, has been reported to inhibit Ca(2+) release through ryanodyne receptors from the endoplasmic reticulum into the cytosol. We designed this study to investigate the neuroprotective effects of dantrolene on hypoxic-ischemic brain damage in the neonatal rat brain. METHODS: Seven-day-old Sprague-Dawley rats were assigned into two groups; control group (n = 69) and dantrolene group (n = 60). Dimethyl sulfoxide was administered intracerebroventricularly in the control group, and dantrolene in dimethyl sulfoxide was similarly administered to the dantrolene group, before hypoxic-ischemic brain injury (HII). HII was induced by the ligation of the common carotid artery under isoflurane anesthesia, followed by exposure to about 2.5 h of hypoxia (oxygen concentration was maintained at 7%-8%). (1)H magnetic resonance spectroscopy was performed 1 day after HII. This noninvasive method evaluated apoptotic processes in the brain after HII. Morphologic score analyses and the calculated percentage of infarct areas after 2,3,5-triphenyltetrazolium chloride staining 14 days after HII were also used to evaluate the effects of dantrolene on HII. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining was performed 1 day after HII using 24 more rats. RESULTS: The lipid/creatine ratios in the right hemispheres in the dantrolene group 1 day after HII were significantly lower than those of the control group (P < 0.05). There was no significant difference between the two groups in the N-acetylaspartate/creatine ratios. The gross morphologic scores were lower in the dantrolene group than in the control group (P < 0.05), and infarct area (%) after 2,3,5-triphenyltetrazolium chloride staining was less in the dantrolene group than in the control group (P < 0.05) 14 days after HII. Further work with 24 rats showed no significant difference, however, in the number of TUNEL positive cells on the two groups. CONCLUSIONS: Our results show that dantrolene, administered intracerebroventricularly before HII, had a neuroprotective effect in HII model of the neonatal rat brain.

The effects of dantrolene on hypoxic-ischemic injury in the neonatal rat brain. Publishing Authors By Initials

M Gwak,P Park,K Kim,K Lim,S Jeong,C Baek,J Lee,M Gwak,P Park,K Kim,K Lim,S Jeong,C Baek,J Lee,

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The effects of dantrolene on hypoxic-ischemic injury in the neonatal rat brain. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Anesthesia and analgesia

VOLUME: 106

Page Numbers: 227-33, table of contents

Journal Abbreviation: Anesth. Analg.

ISSN: 1526-7598

DAY: 31

MONTH: Jan

YEAR: 2008

The effects of dantrolene on hypoxic-ischemic injury in the neonatal rat brain. Information

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LANGUAGE: eng

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AFFILIATION: Department of Anesthesiology and Pain Medicine, Asan Medical Center, College of Medicine, Ulsan University, 388-1 Pungnap-2dong, Songpa-gu, Seoul 138-736, South Korea. phpark@amc.seoul.k.

Country: United States

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MEDLINETA: Anesth Analg

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