A novel murine model of osmotic demyelination syndrome

Joanna Bouchat, Bruno Couturier, Fabrice Gankam Kengne, Charles Nicaise

Research output: Contribution to conferenceAbstract

Abstract

Osmotic demyelination syndrome (ODS) is a severe neurological complication occuring after inadvertant rapid correction of chronic hyponatremia. This pathology primarily affects the CNS and is characterized by large areas of demyelination in centropontine or extrapontine regions, often correlated with neurological symptoms : from lethargia to coma or even death. Historically, the most used ODS animal model is Rattus norvegicus, that mimicked myelin and oligodendrocyte loss and allowed important insights in the management and in the understanding of ODS pathology. According to an adapted protocol from the rat model, we developed a murine model of ODS that will help at unravelling the molecular and cellular pathophysiological mechanisms. Chronic hyponatremia was induced in mice using continuous desmopressin infusion and a low-­‐sodium liquid diet. After 4 days, blood sodium dropped to 112±7 mEq/L in the hyponatremic group (compared to normonatremic group 144±10 mEq/L, p<0.001) and animals showed clinical signs of mild lethargia. ODS was induced by the correction of hyponatremia using a single injection of hypertonic saline targeting a normal range of blood sodium. 24 hours after correction, blood natremia was measured to determine the final 24-­‐hours sodium correction gradient (37±7 mEq/L, p<0.001 between hyponatremia and correction of hyponatremia). Interestingly, mice displayed transient increased overall locomotor activity during the first 12 hours post-­‐correction before a drastic worsening of neurological symptoms, most likely due to occurrence of demyelination. Histopathologically, ODS mice showed large areas of demyelination in subcortical and midbrain regions, attested by loss of myelin in Eriochrome C staining and anti-­‐myelin basic protein immunohistochemistry starting 24 hours after the correction. As early as 24 hours post-­‐correction, mice showed first signs of myelin vacuolization in midbrain regions. Intriguing some ODS mice showed a decreased immunoreactivity of NeuN+ cells in thalamic region. The number of APC+ oligodendrocytes was also reduced in thalamus and cortex. At latter time points (>96 hours post-­‐correction), ODS-­‐affected brain areas (thalamus, cortex) showed significant astrogliosis, as assessed by GFAP immunohistochemistry. Using an anti-­‐mouse IgG staining, we observed plasmatic IgG leakage in the ODS brains between 24 and 48 hours post-­‐correction, suggesting the disruption of the blood-­‐brain barrier. In conclusion, we successfully translated the rat model of ODS to a mouse model and reproduced neurological as well as histological outcomes observed in human cases of ODS.

Meeting

MeetingThe Belgian Society for Cell and Developmental Biology Spring Meeting 2015
CountryBelgium
CityLiège
Period6/06/156/06/15

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Demyelinating Diseases
Thalamus

Cite this

Bouchat, J., Couturier, B., Gankam Kengne, F., & Nicaise, C. (2015). A novel murine model of osmotic demyelination syndrome. Abstract from The Belgian Society for Cell and Developmental Biology Spring Meeting 2015, Liège, Belgium.
Bouchat, Joanna ; Couturier, Bruno ; Gankam Kengne, Fabrice ; Nicaise, Charles. / A novel murine model of osmotic demyelination syndrome. Abstract from The Belgian Society for Cell and Developmental Biology Spring Meeting 2015, Liège, Belgium.
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title = "A novel murine model of osmotic demyelination syndrome",
abstract = "Osmotic demyelination syndrome (ODS) is a severe neurological complication occuring after inadvertant rapid correction of chronic hyponatremia. This pathology primarily affects the CNS and is characterized by large areas of demyelination in centropontine or extrapontine regions, often correlated with neurological symptoms : from lethargia to coma or even death. Historically, the most used ODS animal model is Rattus norvegicus, that mimicked myelin and oligodendrocyte loss and allowed important insights in the management and in the understanding of ODS pathology. According to an adapted protocol from the rat model, we developed a murine model of ODS that will help at unravelling the molecular and cellular pathophysiological mechanisms. Chronic hyponatremia was induced in mice using continuous desmopressin infusion and a low-­‐sodium liquid diet. After 4 days, blood sodium dropped to 112±7 mEq/L in the hyponatremic group (compared to normonatremic group 144±10 mEq/L, p<0.001) and animals showed clinical signs of mild lethargia. ODS was induced by the correction of hyponatremia using a single injection of hypertonic saline targeting a normal range of blood sodium. 24 hours after correction, blood natremia was measured to determine the final 24-­‐hours sodium correction gradient (37±7 mEq/L, p<0.001 between hyponatremia and correction of hyponatremia). Interestingly, mice displayed transient increased overall locomotor activity during the first 12 hours post-­‐correction before a drastic worsening of neurological symptoms, most likely due to occurrence of demyelination. Histopathologically, ODS mice showed large areas of demyelination in subcortical and midbrain regions, attested by loss of myelin in Eriochrome C staining and anti-­‐myelin basic protein immunohistochemistry starting 24 hours after the correction. As early as 24 hours post-­‐correction, mice showed first signs of myelin vacuolization in midbrain regions. Intriguing some ODS mice showed a decreased immunoreactivity of NeuN+ cells in thalamic region. The number of APC+ oligodendrocytes was also reduced in thalamus and cortex. At latter time points (>96 hours post-­‐correction), ODS-­‐affected brain areas (thalamus, cortex) showed significant astrogliosis, as assessed by GFAP immunohistochemistry. Using an anti-­‐mouse IgG staining, we observed plasmatic IgG leakage in the ODS brains between 24 and 48 hours post-­‐correction, suggesting the disruption of the blood-­‐brain barrier. In conclusion, we successfully translated the rat model of ODS to a mouse model and reproduced neurological as well as histological outcomes observed in human cases of ODS.",
author = "Joanna Bouchat and Bruno Couturier and {Gankam Kengne}, Fabrice and Charles Nicaise",
year = "2015",
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note = "The Belgian Society for Cell and Developmental Biology Spring Meeting 2015 ; Conference date: 06-06-2015 Through 06-06-2015",

}

Bouchat, J, Couturier, B, Gankam Kengne, F & Nicaise, C 2015, 'A novel murine model of osmotic demyelination syndrome' The Belgian Society for Cell and Developmental Biology Spring Meeting 2015, Liège, Belgium, 6/06/15 - 6/06/15, .

A novel murine model of osmotic demyelination syndrome. / Bouchat, Joanna; Couturier, Bruno; Gankam Kengne, Fabrice; Nicaise, Charles.

2015. Abstract from The Belgian Society for Cell and Developmental Biology Spring Meeting 2015, Liège, Belgium.

Research output: Contribution to conferenceAbstract

TY - CONF

T1 - A novel murine model of osmotic demyelination syndrome

AU - Bouchat, Joanna

AU - Couturier, Bruno

AU - Gankam Kengne, Fabrice

AU - Nicaise, Charles

PY - 2015

Y1 - 2015

N2 - Osmotic demyelination syndrome (ODS) is a severe neurological complication occuring after inadvertant rapid correction of chronic hyponatremia. This pathology primarily affects the CNS and is characterized by large areas of demyelination in centropontine or extrapontine regions, often correlated with neurological symptoms : from lethargia to coma or even death. Historically, the most used ODS animal model is Rattus norvegicus, that mimicked myelin and oligodendrocyte loss and allowed important insights in the management and in the understanding of ODS pathology. According to an adapted protocol from the rat model, we developed a murine model of ODS that will help at unravelling the molecular and cellular pathophysiological mechanisms. Chronic hyponatremia was induced in mice using continuous desmopressin infusion and a low-­‐sodium liquid diet. After 4 days, blood sodium dropped to 112±7 mEq/L in the hyponatremic group (compared to normonatremic group 144±10 mEq/L, p<0.001) and animals showed clinical signs of mild lethargia. ODS was induced by the correction of hyponatremia using a single injection of hypertonic saline targeting a normal range of blood sodium. 24 hours after correction, blood natremia was measured to determine the final 24-­‐hours sodium correction gradient (37±7 mEq/L, p<0.001 between hyponatremia and correction of hyponatremia). Interestingly, mice displayed transient increased overall locomotor activity during the first 12 hours post-­‐correction before a drastic worsening of neurological symptoms, most likely due to occurrence of demyelination. Histopathologically, ODS mice showed large areas of demyelination in subcortical and midbrain regions, attested by loss of myelin in Eriochrome C staining and anti-­‐myelin basic protein immunohistochemistry starting 24 hours after the correction. As early as 24 hours post-­‐correction, mice showed first signs of myelin vacuolization in midbrain regions. Intriguing some ODS mice showed a decreased immunoreactivity of NeuN+ cells in thalamic region. The number of APC+ oligodendrocytes was also reduced in thalamus and cortex. At latter time points (>96 hours post-­‐correction), ODS-­‐affected brain areas (thalamus, cortex) showed significant astrogliosis, as assessed by GFAP immunohistochemistry. Using an anti-­‐mouse IgG staining, we observed plasmatic IgG leakage in the ODS brains between 24 and 48 hours post-­‐correction, suggesting the disruption of the blood-­‐brain barrier. In conclusion, we successfully translated the rat model of ODS to a mouse model and reproduced neurological as well as histological outcomes observed in human cases of ODS.

AB - Osmotic demyelination syndrome (ODS) is a severe neurological complication occuring after inadvertant rapid correction of chronic hyponatremia. This pathology primarily affects the CNS and is characterized by large areas of demyelination in centropontine or extrapontine regions, often correlated with neurological symptoms : from lethargia to coma or even death. Historically, the most used ODS animal model is Rattus norvegicus, that mimicked myelin and oligodendrocyte loss and allowed important insights in the management and in the understanding of ODS pathology. According to an adapted protocol from the rat model, we developed a murine model of ODS that will help at unravelling the molecular and cellular pathophysiological mechanisms. Chronic hyponatremia was induced in mice using continuous desmopressin infusion and a low-­‐sodium liquid diet. After 4 days, blood sodium dropped to 112±7 mEq/L in the hyponatremic group (compared to normonatremic group 144±10 mEq/L, p<0.001) and animals showed clinical signs of mild lethargia. ODS was induced by the correction of hyponatremia using a single injection of hypertonic saline targeting a normal range of blood sodium. 24 hours after correction, blood natremia was measured to determine the final 24-­‐hours sodium correction gradient (37±7 mEq/L, p<0.001 between hyponatremia and correction of hyponatremia). Interestingly, mice displayed transient increased overall locomotor activity during the first 12 hours post-­‐correction before a drastic worsening of neurological symptoms, most likely due to occurrence of demyelination. Histopathologically, ODS mice showed large areas of demyelination in subcortical and midbrain regions, attested by loss of myelin in Eriochrome C staining and anti-­‐myelin basic protein immunohistochemistry starting 24 hours after the correction. As early as 24 hours post-­‐correction, mice showed first signs of myelin vacuolization in midbrain regions. Intriguing some ODS mice showed a decreased immunoreactivity of NeuN+ cells in thalamic region. The number of APC+ oligodendrocytes was also reduced in thalamus and cortex. At latter time points (>96 hours post-­‐correction), ODS-­‐affected brain areas (thalamus, cortex) showed significant astrogliosis, as assessed by GFAP immunohistochemistry. Using an anti-­‐mouse IgG staining, we observed plasmatic IgG leakage in the ODS brains between 24 and 48 hours post-­‐correction, suggesting the disruption of the blood-­‐brain barrier. In conclusion, we successfully translated the rat model of ODS to a mouse model and reproduced neurological as well as histological outcomes observed in human cases of ODS.

M3 - Abstract

ER -

Bouchat J, Couturier B, Gankam Kengne F, Nicaise C. A novel murine model of osmotic demyelination syndrome. 2015. Abstract from The Belgian Society for Cell and Developmental Biology Spring Meeting 2015, Liège, Belgium.