[Prevention of central pontine myelinolysis in rats by early treatment with dexamethasone]

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Jul;35(4):424-9. doi: 10.3785/j.issn.1008-9292.2006.04.014.
[Article in Chinese]

Abstract

Objective: To explore the effect and mechanism of dexamethasone (DEX) in the prevention of central pontine myelinolysis (CPM) in rats.

Methods: Hyponatremia was induced in rat by subcutaneous injection of Vasopressin Tannate and intraperitoneal injection of 2.5% dextrose in water for 3 d, the rats of Group A received a bolus of 1 mol/L NaCl (2 ml/kg) and DEX (5 mg/kg) simultaneously at the 4th day; the rats of Group B were treated with DEX after 24 h of the injection of 1 mol/L NaCl; the rats in Group C received a bolus of 1 mol/L NaCl and saline simultaneously; Group D was the control group. The demyelinative lesions were evaluated by myelin staining. The Evans blue (EB) contents of brain were detected to evaluate the blood-brain-barrier permeability after rapid correction of hyponatremia. The expression of inducible nitric oxide synthase (iNOS) in brains was evaluated by Western blotting.

Result: CPM was induced successfully in rats. The EB contents of Group A, B and C had no significant difference at 0 h after injection of hypertonic saline compared with Group D. The EB contents of Group C began to increase significantly at 6 h after injection of hypertonic saline, peaked at 24 h; the expression of iNOS in brains began to increase after 3 h after the rapid correction of hyponatremia. The rate of morbidity in Group C was 66.7%. The demyelinative lesions were rarely seen in Group A, the EB contents of brain decreased significantly compared with Group C at the same time point (P<0.05), the iNOS expression was also inhibited. DEX could not prevent the attack of CPM at Group B, the rate of morbidity (75%) had no significant difference compared with Group C (P>0.05).

Conclusion: Early treatment with DEX can protect blood-brain-barrier and inhibit the expression of iNOS to prevent the attack of CPM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / physiopathology
  • Dexamethasone / therapeutic use*
  • Glucocorticoids / therapeutic use
  • Glucose
  • Male
  • Myelinolysis, Central Pontine / chemically induced
  • Myelinolysis, Central Pontine / physiopathology
  • Myelinolysis, Central Pontine / prevention & control*
  • Nitric Oxide Synthase Type II / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vasopressins

Substances

  • Glucocorticoids
  • pitressin tannate
  • Vasopressins
  • Arginine Vasopressin
  • Dexamethasone
  • Nitric Oxide Synthase Type II
  • Glucose