Minocycline prevents osmotic demyelination associated with aquaresis

Hiroshi Takagi, Yoshihisa Sugimura, Haruyuki Suzuki, Shintaro Iwama, Hisakazu Izumida, Haruki Fujisawa, Koichiro Ogawa, Kotaro Nakashima, Hiroshi Ochiai, Seiji Takeuchi, Atsushi Kiyota, Hidetaka Suga, Motomitsu Goto, Ryoichi Banno, Hiroshi Arima, Yutaka Oiso

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13 Citations (Scopus)

Abstract

Overly rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome (ODS). Minocycline protects ODS associated with overly rapid correction of chronic hyponatremia with hypertonic saline infusion in rats. In clinical practice, inadvertent rapid correction frequently occurs due to water diuresis, when vasopressin action suddenly ceases. In addition, vasopressin receptor antagonists have been applied to treat hyponatremia. Here the susceptibility to and pathology of ODS were evaluated using rat models developed to represent rapid correction of chronic hyponatremia in the clinical setting. The protective effect of minocycline against ODS was assessed. Chronic hyponatremia was rapidly corrected by 1 (T1) or 10 mg/kg (T10) of tolvaptan, removal of desmopressin infusion pumps (RP), or administration of hypertonic saline. The severity of neurological impairment in the T1 group was significantly milder than in other groups and brain hemorrhage was found only in the T10 and desmopressin infusion removal groups. Minocycline inhibited demyelination in the T1 group. Further, immunohistochemistry showed loss of aquaporin-4 (AQP4) in astrocytes before demyelination developed. Interestingly, serum AQP4 levels were associated with neurological impairments. Thus, minocycline can prevent ODS caused by overly rapid correction of hyponatremia due to water diuresis associated with vasopressin action suppression. Increased serum AQP4 levels may be a predictive marker for ODS.

Original languageEnglish
Pages (from-to)954-964
Number of pages11
JournalKidney International
Volume86
Issue number5
DOIs
Publication statusPublished - 05-11-2014

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Takagi, H., Sugimura, Y., Suzuki, H., Iwama, S., Izumida, H., Fujisawa, H., Ogawa, K., Nakashima, K., Ochiai, H., Takeuchi, S., Kiyota, A., Suga, H., Goto, M., Banno, R., Arima, H., & Oiso, Y. (2014). Minocycline prevents osmotic demyelination associated with aquaresis. Kidney International, 86(5), 954-964. https://doi.org/10.1038/ki.2014.119