Reinduction of Hyponatremia Improves Survival in Rats with Myelinolysis-related Neurologic Symptoms

Soupart, Alain; Penninckx, Raymond; Stenuit, Alain; Périer, O; Decaux, Guy

doi:10.1097/00005072-199605000-00011

Cited by 61 publications

(23 citation statements)

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“…In contrast, SNa re-lowering was effective in protecting from both neurological manifestations and death in the animal model of ODS. These later findings are in accordance with our previous experiments, 12,13 and support recent clinical evidence of the protective role of re-induction of hyponatremia in the prevention of ODS in humans. [19][20][21] Our experiments suggest that the efficacy of DXM in terms of mortality should be considered with caution and that early re-induction of hyponatremia is to be preferred if the patient has been submitted to extensive correction of hyponatremia.…”

Section: Discussionsupporting

confidence: 92%

“…Blood samples were taken for serum analysis, and only rats that achieved an SNa gradient of correction X25 mEq/l were treated with re-induction of hyponatremia. Hyponatremia was re-induced by an intraperitoneal administration of water (10% of body weight) to achieve a final SNa gradient p20 mEq/l over 24 h. 12,13 Groups 1 and 2 included only rats with a 24-h SNa gradient X25 mEq/l. This value of SNa gradient has been previously shown to be inevitably associated with brain demyelinative lesions in animals corrected with NaCl alone.…”

Section: Evaluation Of Neurological Manifestations and Mortalitymentioning

confidence: 99%

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Re-induction of hyponatremia after rapid overcorrection of hyponatremia reduces mortality in rats

Kengne

Soupart

Pochet

et al. 2009

Kidney International

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Osmotic demyelination syndrome is a devastating neurologic disorder often seen after the rapid correction of chronic hyponatremia. The permeability of the blood-brain barrier is increased in experimental osmotic demyelination, and some have suggested that corticosteroids protect against this disorder by keeping the permeability of the blood-brain barrier low. We previously reported that re-lowering of the serum sodium after rapid correction of chronic hyponatremia was beneficial if performed early in the course (12 to 24 h). Here we compared mortality, blood-brain barrier permeability, and microglial activation in rats after the rapid correction of chronic hyponatremia. We studied three groups of rats after correction of chronic hyponatremia: and treated them with sodium chloride, with or without dexamethasone; or with sodium chloride followed by re-induction of hyponatremia. We found that treatment with dexamethasone or re-induction of hyponatremia effectively prevented the opening of the blood-brain barrier, reduced neurological manifestations, and decreased microglial activation; however, only re-induction of hyponatremia resulted in a significant decrease in mortality 5 days after the correction of chronic hyponatremia. Restoring the permeability of the blood-brain barrier to normal levels did not decrease mortality. Our results suggest that after inadvertent rapid correction of hyponatremia, treatment options should favor re-lowering serum sodium. The increased permeability of blood-brain barrier seen in osmotic demyelination syndrome may not be a primary pathophysiologic insult of this syndrome.

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Section: Discussionsupporting

confidence: 92%

Section: Evaluation Of Neurological Manifestations and Mortalitymentioning

confidence: 99%

Re-induction of hyponatremia after rapid overcorrection of hyponatremia reduces mortality in rats

Kengne

Soupart

Pochet

et al. 2009

Kidney International

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“…Rapidly induced and sustained severe hypernatremia has also been shown to cause brain myelinolysis in rats, but a large serum Na ϩ gradient (⌬Na) (39Ϯ8 mEq/L) was necessary to demonstrate myelin injury. 24 The ⌬Na in our study was only Ϸ17 mEq/L. Maintenance of this ⌬Na for 4 days without ischemia did not cause myelin injury.…”

Section: Discussionmentioning

confidence: 44%

Hypertonic Saline Worsens Infarct Volume After Transient Focal Ischemia in Rats

Bhardwaj

Harukuni

Murphy

et al. 2000

Stroke

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Background and Purpose-Hypertonic saline (HS) has been advocated as a hyperosmolar agent for the treatment of cerebral edema, especially after traumatic brain injury. We tested the hypothesis that continuous intravenous HS administered during reperfusion from transient focal cerebral ischemia attenuates infarct volume. Methods-Halothane-anesthetized male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. At the onset of reperfusion, rats received a 10-mL/kg intravenous bolus of 0.9% saline (SAL, nϭ8) or 7.5% SAL (chloride:acetate 50:50, nϭ8) followed by a continuous infusion for 22 hours. In a second series of experiments, ischemic damage was determined in cohorts treated with equivolumetric 3% saline (nϭ8) or 20% mannitol (nϭ8). In a third series, regional cerebral blood flow was measured ([ 14 C]iodoantipyrine autoradiography) at 6 hours of reperfusion in 7.5%-SAL-treated (nϭ5) or SAL-treated (nϭ5) animals. Results-In SAL rats, serum Na ϩ was 137Ϯ3 and 138Ϯ2 mEq/L (meanϮSEM) at baseline and 22 hours of reperfusion, respectively. In 7.5% SAL, serum Na ϩ was 136Ϯ2 and 154Ϯ2 mEq/L at baseline and reperfusion, respectively. Physiological variables and reduction in laser-Doppler signal during MCAO and early reperfusion were not different between the 2 treatment groups. Cortical infarct volume was larger in 7.5%-SAL-treated rats (121Ϯ14 mm 3 ; 30Ϯ3% of contralateral cortex; PϽ0.05) than in SAL (64Ϯ15 mm 3 ; 16Ϯ4% of contralateral cortex). Striatal infarct volume was unchanged by HS therapy. Ipsilateral cortical tissue volume was increased relative to the contralateral side (by 26Ϯ5% with SAL; by 41Ϯ5% with 7.5% SAL). In contrast, ischemic damage was unaffected by 3%-SAL or 20%-mannitol treatment compared with SAL. Regional cerebral blood flow during reperfusion was heterogeneous in all animals, but there was no evidence of postischemic hypoperfusion or blood flow maldistribution in 7.5%-SAL-treated animals.Conclusions-These data demonstrate that hypernatremia resulting from postischemic HS infusion worsens cortical infarct volume in transient focal cerebral ischemia. The deleterious effect is not linked to exacerbation of delayed hypoperfusion during early reperfusion (6 hours); however, blood flow defects at later recovery time points remain to be excluded. These results may have implications for HS therapy in clinical ischemic stroke. (Stroke.

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“…Thus far, re-lowering serum sodium is the most beneficial treatment when the initial osmotic injury has already occurred. 6,[33][34][35] Our results suggest that, in clinical practice, early administration of minocycline might have a role in preventing neurologic damage in hyponatremic patients who underwent rapid correction of their sodium deficit. Nevertheless, re-lowering of serum sodium should remain the treatment of choice when a toxic gradient is achieved until further work is done to fully explore the possibilities of minocycline in management of rapid correction of chronic hyponatremia in terms of the minimal effective dose and possible combination with re-lowering of serum sodium.…”

Section: Discussionmentioning

confidence: 69%

Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia

Gankam-Kengne

Soupart

Pochet

et al. 2010

Journal of the American Society of Nephrology

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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 bloodbrain barrier, inhibited microglial activation, decreased both the expression of IL1␣ 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. Osmotic demyelination syndrome (ODS) is a severe neurologic condition that is characterized by severe demyelination in the central nervous system (CNS) secondary to osmotic imbalance. In a clinical setting, this syndrome often occurs after too rapid correction of chronic hyponatremia. [1][2][3][4][5] In ODS, demyelination is widespread in the brain, with predominance in hippocampus, basal ganglia, and subcortical regions. The physiopathology of this disorder is not yet fully understood, and an experimental murine model has been developed to better understand the mechanisms leading to myelin damage after an osmotic injury. 2,5,6 Previous experiments have suggested that ODS might share key characteristics with other models of central nervous system demyelination in which both opening of the blood-brain barrier (BBB) and microglia-macrophage activation are involved in the genesis of demyelinative changes. [7][8][9][10][11] Minocycline is a second-generation tetracycline that has been well studied in various models of brain pathology including autoimmune or ischemic myelin damage, and others have reported that administration of minocycline in CNS injury was associated with a striking reduction in BBB permeability, inhibition of microglia-macrophage activation, and inflammatory

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Reinduction of Hyponatremia Improves Survival in Rats with Myelinolysis-related Neurologic Symptoms

Cited by 61 publications

References 0 publications

Re-induction of hyponatremia after rapid overcorrection of hyponatremia reduces mortality in rats

Re-induction of hyponatremia after rapid overcorrection of hyponatremia reduces mortality in rats

Hypertonic Saline Worsens Infarct Volume After Transient Focal Ischemia in Rats

Minocycline Protects against Neurologic Complications of Rapid Correction of Hyponatremia

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