title: Transient body fluid accumulation and enhanced NKCC2 expression in gerbils with brain infarction.
abstract: BACKGROUND
  Enhanced expression of a kidney-specific sodium co-transporter (NKCC2: Na-K-2Cl co-transporter) in the thick ascending limb of Henle has been identified in rat models of congestive heart failure and liver cirrhosis, suggesting that high NKCC2 expression underlies edema formation. An increased abundance of NKCC2, however, has also been noted in rats with the syndrome of inappropriate secretion of antidiuretic hormone; hyponatremia without edema. In the present study, we examined NKCC2 expression in non-edematous disease, such as a brain infarction, and investigated the physiological and/or pathological characterization of NKCC2 expression.
  
  
  METHODS
  We initially examined NKCC2 expression in an animal model of brain infarction. Mongolian gerbils (around 60 g body weight) underwent bilateral clamping of the common carotid arteries for 5 min for the induction of brain infarction. NKCC2 and apical water channel (AQP2) protein levels in the collecting duct were examined by Western blotting in kidney tissues 2, 7, and 14 days after the brain infarction. Gerbils with brain infarction were then fed either a normal low-sodium diet (0.3 g/kg/day) or a high-sodium diet (3.0 g/kg/day), and body weight, urine volume and urinary osmolality were examined daily. Blood parameters were measured on day 14 after the brain infarction.
  
  
  RESULTS
  Histochemical examination of the brain confirmed the presence of brain infarction, as manifested by altered cresyl violet staining in the hippocampus. Protein levels of NKCC2 were significantly increased in gerbils with brain infarction on days 2 and 7 after brain infarction, whereas AQP2 protein signals remained unaltered. However, the increased NKCC2 intensity disappeared on day 14. Body weight gain was slightly, but significantly greater in gerbils with brain infarction than in sham-operated gerbils up to 7 days after the brain infarction. The high-sodium diet resulted in significant urinary concentration and enhanced weight gain in infarcted gerbils.
  
  
  CONCLUSIONS
  We noted increased NKCC2 abundance in non-edematous disease, which enhanced body fluid accumulation, likely via the sodium loading-dependent concentration of the urine. These results suggest that the physiological process of edema formation is based on specific NKCC2 expression. The transient duration of these findings in the present animal model suggests two different characteristics of specific NKCC2 expression, an immediate, transient appearance as a common response in serious conditions and more chronic expression that leads to edema formation.
authors.affiliation: Division of Molecular Medicine, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ejima
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Mari
authors.initials: M
authors.lastname: Michimata
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatano
authors.forename: Itsuro
authors.initials: I
authors.lastname: Kazama
authors.forename: Satoru
authors.initials: S
authors.lastname: Sanada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Arata
authors.forename: Michiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Miyama
authors.forename: Akira
authors.initials: A
authors.lastname: Sato
authors.forename: Susumu
authors.initials: S
authors.lastname: Satomi
authors.forename: Shinji
authors.initials: S
authors.lastname: Fushiya
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Matsubara
mesh_terms: D000818:Animals; D001826:Body Fluids / Q000378:metabolism*; D020520:Brain Infarction / Q000097:blood / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D005849:Gerbillinae; D008297:Male; D028021:Sodium-Potassium-Chloride Symporters / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D015854:Up-Regulation / Q000502:physiology*
chemical_list: C578716:Slc12a1 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1