title: Changes in cerebral blood flow and distribution associated with acute increases in plasma sodium and osmolality of chronic hyponatremic rats.
abstract: The cause of the osmotic demyelination syndrome that follows too rapid correction of chronic hyponatremia (CHN) is unknown. Recently, we reported in CHN rats an association between blood-brain barrier (BBB) disruption occurring as early as 3 h into correction and subsequent demyelination. Given the changes in brain water and blood volume which occur during correction of CHN, we hypothesized that the same correction protocol that causes demyelination might alter cerebral blood flow (CBF) during correction, thereby possibly contributing to BBB disruption and demyelination. Ten CHN rats were given hypertonic sodium intraperitoneally and its effect on CBF was continuously monitored for 3 h by magnetic resonance flow imaging. Over the subsequent 3 h, plasma sodium rose from 110.8 to 127.6 mEq/liter (P < 0.001) but neither mean arterial blood pressure nor arterial CO(2) tension changed significantly. By 30 min, CBF increased by 50% in cortical and subcortical areas (P < 0.001) and remained elevated for the next 60 min. After 2 h, cortical flow was no longer elevated significantly and by 3 h it had returned to control values. Subcortical flow, however, significantly exceeded control values throughout the 3 h so that after 2 h the ratio of cortical to subcortical blood flow had fallen from 1.17 to 0.91 (P < 0.05). Although the mechanism by which increased plasma sodium and osmolality alters CBF is uncertain, the results suggest that changes in CBF may be part of a cascade of cerebrovascular disturbances including endothelial or parenchymal damage, mechanical events, metabolic disturbances, or cytokine release which eventually lead to BBB disruption and subsequent demyelination.
authors.affiliation: Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: S
authors.initials: S
authors.lastname: Adler
authors.forename: J G
authors.initials: JG
authors.lastname: Verbalis
authors.forename: S
authors.initials: S
authors.lastname: Meyers
authors.forename: E
authors.initials: E
authors.lastname: Simplaceanu
authors.forename: D S
authors.initials: DS
authors.lastname: Williams
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007010:Hyponatremia / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology*; D007263:Infusions, Parenteral; D007552:Isotonic Solutions / Q000494:pharmacology; D018810:Magnetic Resonance Angiography; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000627:therapeutic use; D012964:Sodium / Q000097:blood*
chemical_list: D007552:Isotonic Solutions; D012462:Saline Solution, Hypertonic; D012964:Sodium