Effect of acute and chronic hyponatremia on blood-brain barrier function in the rat.
To study whether acute or chronic hyponatremia alters blood-brain barrier (BBB) permeability, rats made hyponatremic by constant desmopressin acetate infusion were studied by NMR spectroscopy and imaging. On constant volume ventilation and nitrous oxide, acute (1- and 2-day) and chronic (7- and 14-day) hyponatremic and normonatremic controls were infused with 0.25 M HCl. Despite reducing blood pH by at least 0.35 in < 50 min, brain pH, measured by 31P NMR, was unaffected in any group. As a second test of BBB function, gadolinium-DTPA (Gd-DTPA) was injected intravenously in these five groups. Coronal slice 1H NMR images obtained before and after Gd-DTPA showed image intensity changes in multiple areas outside brain, but neither control nor hyponatremic rats showed any differences in cortex, white matter or cerebellum. To ascertain whether the threshold for BBB disruption was altered, hypertonic mannitol (1.5, 2.0 or 3.0 mL) was injected rapidly into one internal carotid artery and pre- and post-Gd-DTPA images obtained. In both control and hyponatremic rats only the largest dose caused detectable Gd-DTPA leakage into brain. Thus, BBB function appears intact in both acute and chronic hyponatremia since neither H+ nor GD-DTPA penetrated the barrier and resistance to mannitol disruption was unaffected by hyponatremia.
Department of Medicine, Montefiore Hospital, University of Pittsburgh School of Medicine, PA.
S
S
Adler
D
D
Williams
J G
JG
Verbalis
D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002908:Chronic Disease; D003287:Contrast Media / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D019786:Gadolinium DTPA; D006851:Hydrochloric Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007010:Hyponatremia / Q000378:metabolism / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D004369:Pentetic Acid / Q000493:pharmacokinetics; D010758:Phosphorus; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D009942:Organometallic Compounds; D010758:Phosphorus; D008353:Mannitol; D004369:Pentetic Acid; D019786:Gadolinium DTPA; D006851:Hydrochloric Acid