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

Research output: Contribution to journalArticle

11 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

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Minocycline
Demyelinating Diseases
Hyponatremia
Aquaporin 4
Deamino Arginine Vasopressin
Diuresis
Vasopressins
Infusion Pumps
Water
Intracranial Hemorrhages
Serum
Astrocytes
Immunohistochemistry
Pathology

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Takagi, H., Sugimura, Y., Suzuki, H., Iwama, S., Izumida, H., Fujisawa, 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
Takagi, Hiroshi ; Sugimura, Yoshihisa ; Suzuki, Haruyuki ; Iwama, Shintaro ; Izumida, Hisakazu ; Fujisawa, Haruki ; Ogawa, Koichiro ; Nakashima, Kotaro ; Ochiai, Hiroshi ; Takeuchi, Seiji ; Kiyota, Atsushi ; Suga, Hidetaka ; Goto, Motomitsu ; Banno, Ryoichi ; Arima, Hiroshi ; Oiso, Yutaka. / Minocycline prevents osmotic demyelination associated with aquaresis. In: Kidney International. 2014 ; Vol. 86, No. 5. pp. 954-964.
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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, vol. 86, no. 5, pp. 954-964. https://doi.org/10.1038/ki.2014.119

Minocycline prevents osmotic demyelination associated with aquaresis. / Takagi, Hiroshi; Sugimura, Yoshihisa; Suzuki, Haruyuki; Iwama, Shintaro; Izumida, Hisakazu; Fujisawa, Haruki; Ogawa, Koichiro; Nakashima, Kotaro; Ochiai, Hiroshi; Takeuchi, Seiji; Kiyota, Atsushi; Suga, Hidetaka; Goto, Motomitsu; Banno, Ryoichi; Arima, Hiroshi; Oiso, Yutaka.

In: Kidney International, Vol. 86, No. 5, 05.11.2014, p. 954-964.

Research output: Contribution to journalArticle

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T1 - Minocycline prevents osmotic demyelination associated with aquaresis

AU - Takagi, Hiroshi

AU - Sugimura, Yoshihisa

AU - Suzuki, Haruyuki

AU - Iwama, Shintaro

AU - Izumida, Hisakazu

AU - Fujisawa, Haruki

AU - Ogawa, Koichiro

AU - Nakashima, Kotaro

AU - Ochiai, Hiroshi

AU - Takeuchi, Seiji

AU - Kiyota, Atsushi

AU - Suga, Hidetaka

AU - Goto, Motomitsu

AU - Banno, Ryoichi

AU - Arima, Hiroshi

AU - Oiso, Yutaka

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N2 - 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.

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