Minocycline prevents osmotic demyelination associated with aquaresis.
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.
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hiroshi
H
Takagi
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yoshihisa
Y
Sugimura
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Haruyuki
H
Suzuki
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Shintaro
S
Iwama
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hisakazu
H
Izumida
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Haruki
H
Fujisawa
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Koichiro
K
Ogawa
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Kotaro
K
Nakashima
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hiroshi
H
Ochiai
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Seiji
S
Takeuchi
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Atsushi
A
Kiyota
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hidetaka
H
Suga
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Motomitsu
M
Goto
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Ryoichi
R
Banno
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hiroshi
H
Arima
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yutaka
Y
Oiso
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000633:toxicity*; D051401:Aquaporin 4 / Q000097:blood; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection; D003894:Deamino Arginine Vasopressin; D003711:Demyelinating Diseases / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000517:prevention & control* / Q000523:psychology; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects*; D007010:Hyponatremia / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009995:Osmosis; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000633:toxicity*; D012964:Sodium / Q000097:blood; D013812:Therapeutics / Q000009:adverse effects*; D013997:Time Factors; D000077602:Tolvaptan; D014882:Water-Electrolyte Balance / Q000187:drug effects
D065092:Antidiuretic Hormone Receptor Antagonists; C496032:Aqp4 protein, rat; D051401:Aquaporin 4; D001552:Benzazepines; D015415:Biomarkers; D018925:Chemokines; D016207:Cytokines; D018696:Neuroprotective Agents; D012462:Saline Solution, Hypertonic; D000077602:Tolvaptan; D012964:Sodium; D020782:Matrix Metalloproteinases; D003894:Deamino Arginine Vasopressin; D008911:Minocycline