Protective effect of dexamethasone on osmotic-induced demyelination in rats

Sugimura, Yoshihisa; Murase, Takashi; Takefuji, Seiko; Hayasaka, Shizu; Takagishi, Yoshiko; Oiso, Yutaka; Murata, Yoshiharu

doi:10.1016/j.expneurol.2004.10.018

Cited by 80 publications

(62 citation statements)

References 26 publications

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“…Rats had ad libitum access to standard chow and tap water until the induction of hyponatremia according to previously described methods. [51][52][53] Briefly, osmotic minipumps (Alzet model 2002 or 2004; DURECT Corporation, Cupertino, CA) containing dDAVP (10 mg/ml; Kyowa Hakko Kogyo Co. Ltd., Tokyo, Japan) were implanted subcutaneously into rats under ether anesthesia. For the moderately or severely hyponatremic groups, dDAVP was injected continuously at rates of 0.3 or 0.7 ng/h, respectively.…”

Section: Animal Experimentsmentioning

confidence: 99%

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Fujisawa

Sugimura

Takagi

et al. 2016

Journal of the American Society of Nephrology

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Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3-CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.

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Section: Animal Experimentsmentioning

confidence: 99%

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Fujisawa

Sugimura

Takagi

et al. 2016

Journal of the American Society of Nephrology

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“…Hyponatremia was induced in rats using the previously described methods. 8,30 Briefly, osmotic minipumps (Alzet model 2002; Alza, Palo Alto, California) containing the vasopressin V2 receptor agonist, 1-deamino-8-D-arginine vasopressin (dDAVP, 10 g/ml; Kyowa Hakko Kogyo Co. Ltd., Tokyo, Japan) were implanted subcutaneously under ether anesthesia, and dDAVP was injected continuously at a rate of 5 ng/h. After 2 days of dDAVP administration, the rats were water loaded by substituting their daily feed with a liquid formula (Isocal plus; MeadJohnson, Evansville, Indiana).…”

Section: Animal Experimentsmentioning

confidence: 99%

“…8 We also reported that the microglia that accumulate in the demyelinative lesions may play a detrimental role in the pathogenesis of ODS by producing proinflammatory cytokines. 9 Minocycline is a semisynthetic tetracycline derivative that exerts anti-inflammatory effects independent of its antimicrobial action.…”

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confidence: 99%

Minocycline Prevents Osmotic Demyelination Syndrome by Inhibiting the Activation of Microglia

Suzuki

Sugimura

Iwama

et al. 2010

Journal of the American Society of Nephrology

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Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome (ODS), a severe demyelination disease. The microglia that accumulate in the demyelinative lesions may play a detrimental role in the pathogenesis of ODS by producing proinflammatory cytokines, suggesting that they may be a target for therapeutic intervention. Here, we investigated whether minocycline, a selective and potent inhibitor of microglial activation, could protect against ODS in rats. We induced hyponatremia by liquid diet feeding and dDAVP infusion. Rapid correction of the hyponatremia 7 days later resulted in neurologic impairment with severe demyelinative lesions. Activated microglia accumulated at the site of demyelination. Treatment with minocycline within 24 hours of rapid correction, however, was protective: rats exhibited minimal neurologic impairment, and survival improved. Histologic analysis showed that minocycline inhibited demyelination and suppressed the accumulation of microglia at the site of demyelination. Real-time RT-PCR and immunohistochemical analyses showed that minocycline inhibited the activity of microglia and the expression of inflammatory cytokines (e.g. IL-1␤, inducible nitric-oxide synthase, and TNF-␣), monocyte chemoattractant protein-1, and matrix metalloproteinase-12 in microglia. These results demonstrate that minocycline can protect against ODS by inhibiting the activation and accumulation of microglia at the site of demyelinative lesions, suggesting its possible use in clinical practice.

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“…Others have reported complete recoveries after steroid administration 10 . Early dexametasone treatment can prevent the blood-brain barrier disruption that is caused by the rapid correction of hyponatremia and its associative demyelinative changes and suggest that dexametasone might be effective in preventing CPM, but these are experimental data 28 …”

Section: Discussionmentioning

confidence: 89%

Pontine and extrapontine osmotic myelinolysis after the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report

Twardowschy

Bertolucci

Gracia

2007

Arq. Neuro-Psiquiatr.

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-Osmotic demyelination syndrome (ODS) may be precipitated by aggressive correction of a hypo or hyper-osmolar states. We describe the case of a 53-year-old woman that was started on fluoxetine 20 mg/day for depression and nine days later was found to have fluoxetine-induced syndrome of inappropriate secretion of antidiuretic hormone. After hyponatremia correction the mental status of the patient gradually improved, but subsequently she had intermittent difficulty in speaking, naming objects, memory deficits and psychomotor slowness. Magnetic resonance revealed bilateral symmetric hyperintense lesions in the basal ganglia, temporal lobe and hippocampal formation compatible with ODS. These symptoms gradually resolved and she was discharged home without any deficits. Two months later, a new image showed lesion in pons and the other lesions had disappeared. Fluoxetine therapy had never been related with a complication like that.KEY WORDS: central pontine and extrapontine myelinolysis, osmotic demyelination syndrome, hyponatremia, fluoxetine.Mielinólise osmótica pontina e extrapontina após a síndrome da secreção inapropriada de hormônio antidiurético associada com fluoxetina: relato de caso RESUMO -A síndrome de desmielinização osmótica (SDO) pode ser precipitada pela correção agressiva de um estado hiper ou hipoosmolar. Nós descrevemos o caso de mulher de 53 anos que havia iniciado o uso de fluoxetina 20 mg/dia para depressão e que nove dias depois foi diagnosticada como tendo síndrome da secreção inapropriada de hormônio antidiurético induzida por fluoxetina. Depois da correção da hiponatremia o estado mental da paciente gradualmente melhorou, mas subsequentemente ela apresentou dificuldade intermitente para fala e para nomear objetos, déficits de memória recente e lentidão psicomotora. Ressonância magnética revelou lesões hiperintensas bilaterais e simétricas na região dos gânglios da base, lobo temporal e hipocampo compatíveis com SDO. Estes sintomas gradualmente se resolveram e a paciente foi de alta sem qualquer déficit. Dois meses mais tarde uma nova imagem cerebral mostrou lesão na ponte e ausência das lesões antigas. Até onde sabemos a terapia com fluoxetina nunca foi relacionada a uma complicação tardia como esta. PALAVRAS-CHAVE: mielinólise central pontina e extrapontina, síndrome de desmielinização osmótica, hiponatremia, fluoxetina.

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Protective effect of dexamethasone on osmotic-induced demyelination in rats

Cited by 80 publications

References 26 publications

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Chronic Hyponatremia Causes Neurologic and Psychologic Impairments

Minocycline Prevents Osmotic Demyelination Syndrome by Inhibiting the Activation of Microglia

Pontine and extrapontine osmotic myelinolysis after the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with fluoxetine: case report

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