Minocycline protects against neurologic complications of rapid correction of hyponatremia.
Osmotic demyelination syndrome is a devastating neurologic condition that occurs after rapid correction of serum sodium in patients with hyponatremia. Pathologic features of this injury include a well-demarcated region of myelin loss, a breakdown of the blood-brain barrier, and infiltration of microglia. The semisynthetic tetracycline minocycline is protective in some animal models of central nervous system injury, including demyelination, suggesting that it may also protect against demyelination resulting from rapid correction of chronic hyponatremia. Using a rat model of osmotic demyelination syndrome, we found that treatment with minocycline significantly decreases brain demyelination, alleviates neurologic manifestations, and reduces mortality associated with rapid correction of hyponatremia. Mechanistically, minocycline decreased the permeability of the blood-brain barrier, inhibited microglial activation, decreased both the expression of IL1α and protein nitrosylation, and reduced the loss of GFAP immunoreactivity. In conclusion, minocycline modifies the course of osmotic demyelination in rats, suggesting its possible therapeutic use in the setting of inadvertent rapid correction of chronic hyponatremia in humans.
Research Unit on Hydromineral Metabolism, Erasme University Hospital, Brussels, Belgium. fgankamk@ulb.ac.be
Fabrice
F
Gankam-Kengne
Alain
A
Soupart
Roland
R
Pochet
Jean Pierre
JP
Brion
Guy
G
Decaux
D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D003711:Demyelinating Diseases / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005455:Fluorescent Antibody Technique; D007010:Hyponatremia / Q000150:complications / Q000188:drug therapy*; D007150:Immunohistochemistry; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D009995:Osmosis; D011897:Random Allocation; D051381:Rats; D018709:Statistics, Nonparametric; D015996:Survival Rate
D008911:Minocycline