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Bumetanide and HOE642 administered after initiation of rat middle cerebral artery occlusion effectively reduce rat brain Na uptake and infarct
Author(s) -
Chen YiJe,
Anderson Steven E.,
O'Donnell Martha E.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.614.6
Subject(s) - bumetanide , cotransporter , ischemia , medicine , brain edema , edema , anesthesia , stroke (engine) , blood–brain barrier , cerebral edema , sodium–hydrogen antiporter , chemistry , middle cerebral artery , pharmacology , endocrinology , sodium , central nervous system , mechanical engineering , organic chemistry , engineering
Increased brain Na uptake across an intact blood‐brain barrier (BBB) contributes to cerebral edema formation in the early hours of ischemic stroke. We have shown previously that a luminal BBB Na‐K‐Cl cotransporter and Na/H exchanger are stimulated by ischemic factors and that both edema and infarct induced by middle cerebral artery occlusion (MCAO) are reduced by i.v. bumetanide or HOE642, inhibitors of the cotransporter and exchanger, respectively. The present study was conducted to determine whether bumetanide and HOE642 reduce the brain Na uptake that underlies edema in ischemic stroke and further, whether they are effective when given after the onset of ischemia. Rats were given bumetanide (30 mg/kg), HOE642 (30 mg/kg) or vehicle i.v. 20 min before, or 1 or 2 hr after initiation of left MCAO. Localized 23Na magnetic resonance spectroscopy with the shift reagent DyTTHA was used to assess total and extravascular brain [Na] in selected regions of interest during up to 5 hr of MCAO. The ipsilateral/contralateral brain ratios of both total [Na] and extravascular [Na] increased linearly following induction of ischemia. Bumetanide and HOE642 significantly reduced brain Na uptake and infarct when given before or after the start of MCAO. Our findings suggest that inhibition of the Na‐K‐Cl cotransporter and Na/H exchanger, even 2 hr after the start of ischemia, effectively reduces brain Na uptake and infarct. Supported by NINDS