title: Bumetanide protects focal cerebral ischemia-reperfusion injury in rat.
abstract: OBJECTIVE
  Bumetanide has been reported to attenuate ischemia-evoked cerebral edema. However, whether bumetanide can protect cerebral ischemia-reperfusion injury (IRI) in vivo is unclear. In the present study, we aim to determine whether intravenously injection bumetanide can attenuate cerebral IRI and if its protection effect might be related to the modification of cerebral NKCC1 and KCC2 protein expression.
  
  
  METHODS
  Focal cerebral ischemia was induced by occluding the right middle cerebral artery (MCAO) for 2-h, followed by 3-h, 24-h or 48-h of reperfusion respectively. Brain edema, neurological deficits, and infarction volume were determined by (wet weights-dry weights)/dry weights×100, 5-point neurological function score evaluation system, and TTC staining, respectively. The expression levels of NKCC1 and KCC2 were determined by immunohistochemical staining.
  
  
  RESULTS
  Reperfusion increased brain edema, neurological deficits, and infarction volume. Bumetanide decreased brain edema, attenuated the neurological defects and reduced post-ischemic cerebral infarction. Cerebral ischemia-reperfusion injury increased NKCC1 expression level and decreased KCC2 expression level. Interestingly, bumetanide down-regulated the NKCC1 protein expression level without changing the KCC2 protein expression level in rat brain cortex.
  
  
  CONCLUSIONS
  These results suggest that bumetanide protects focal cerebral ischemia-reperfusion injury in rat, which might through the inhibition of NKCC1.
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Guangzhou Medical University Guangzhou 510260, China ; Department of Anesthesiology, Affiliated Zhong San Chinese Hospital of Guang Zhou Chinese University Zhong San 528400, China.
authors.forename: Genbao
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Guangzhou Medical University Guangzhou 510260, China.
authors.forename: Huansen
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Guangzhou Medical University Guangzhou 510260, China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Guangzhou Medical University Guangzhou 510260, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ruan
authors.affiliation: Department of Anesthesiology, Second Affiliated Hospital of Guangzhou Medical University Guangzhou 510260, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Huang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002034:Bumetanide / Q000008:administration & dosage / Q000627:therapeutic use*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D064506:Solute Carrier Family 12, Member 2 / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D013997:Time Factors; D000096922:K Cl- Cotransporters
chemical_list: D002034:Bumetanide; D049994:Sodium Potassium Chloride Symporter Inhibitors; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D000096922:K Cl- Cotransporters
keywords: Bumetanide; Na+-K+-Cl--cotransporter 1 (NKCC1); Na+-K+-cotransporter 2 (KCC2); cerebral ischemia-reperfusion injury; neuroprotection