title: Brain osmoregulation during extreme and moderate dehydration in a rat model of severe DKA.
abstract: To determine if osmoprotective molecules accumulate in the brain during severe DKA with extreme (DKA-E) and moderate (DKA-M) dehydration, Fischer 344 rats (250-350g) were given STZ 45 mg/kg (i.p.) and allowed food and water ad lib. DKA-M received NaCl 77 mmol/L 60 ml/kg (i.p.) q 4 hrs. on day 2. All rats were anesthetized and sacrificed at 48 hrs. Half of each brain was used to measure water content (BWC) and half to measure Na+, K+, and organic osmoles by HPLC. Just prior to expiration, values for mean concentration of serum glucose (mmol/L) percent weight loss and median blood pH for DKA-E were 33.4, 19%, 6.98; for DKA-M, 16.8, 7.5% and 6.84, respectively. Means +/- SEM were compared by Student's t-test. Percent BWC was 76.3, 77.3 and 77.6 in DKA-E, DKA-M and normal controls, respectively (NS). Brain Na+ and K+ were increased in DKA-M compared to controls (p < .05) but not significantly different in DKA-E compared to controls. Of organic osmoles measured (umol/g wet weight) taurine was significantly increased (p < .01) in DKA-E and DKA-M (8.04 +/- .39 and 9.73 +/- .78, respectively) as compared to controls (5.92 +/- .35) as was myoinositol in DKA-E compared to controls (9.96 +/- .39 vs. 8.87 +/- .28) (p < .05) and urea in DKA-E as compared to controls (14.24 +/- 3.9 vs. 4.14 +/- .52) (p < .01). DKA-M were not significantly different for brain myoinositol or urea as compared to control animals. There was no significant difference in brain glutamine between either study group and controls. Preservation of brain water despite systemic dehydration can be partly explained by increased brain concentrations of osmoprotective molecules. Such adaption in the clinical setting of DKA warrants a cautious repair of dehydration and hyperosmolality.
authors.affiliation: Department of Pediatrics, VAMC, Buffalo.
authors.forename: G D
authors.initials: GD
authors.lastname: Harris
authors.forename: J W
authors.initials: JW
authors.lastname: Lohr
authors.forename: I
authors.initials: I
authors.lastname: Fiordalisi
authors.forename: M
authors.initials: M
authors.lastname: Acara
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001834:Body Water; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D003681:Dehydration / Q000209:etiology / Q000503:physiopathology*; D016883:Diabetic Ketoacidosis / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000378:metabolism; D013311:Streptozocin; D014882:Water-Electrolyte Balance
chemical_list: D001786:Blood Glucose; D013311:Streptozocin; D012964:Sodium; D011188:Potassium