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2019

ANUÁRIO DO HOSPITAL
DONA ESTEFÂNIA

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CSF STUDY OF CATION-CHLORIDE COTRANSPORTERS MAY IMPROVE RATIONAL TREATMENT OF EARLY SEIZURES

Sofia Duarte1, Carlos Ortez2, Rafael Arturch2, Mercedes Pineda2, Eulalia Calado1, Angels Garcia Cazorla2.

1 – Serviço Neurologia, Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central, E.P.E.;
2 - Hospital San Joan de Deu, Barcelona, Spain.

- 12th International Child Neurology Congress and the 11th Asian and Oceanian Congress of Child Neurology, 27 May-1 June 2012, Brisbane, Australia.
- Abstract published in Developmental Medicine and Child Neurology, Volume 54, Issue Supplement s4.

Objective: During early development, GABAA–receptor mediated responses are often depolarizing, and later evolve to a mature pattern of neuronal hyperpolarization when activated. This functional switch has been attributed to age-related differences in the relative abundance of cation chloride cotransporters, such as KCC2 and NKCC1, which regulate chloride homeostasis.

Design: Prospective population study. Method: In order to better characterize evolving changes of molecules that play a key role in this process, in humans and in vivo, NKCC1 and KCC2 were analysed in cerebrospinal fluid samples from 58 healthy paediatric controls (from 1d to 14years of life) by immunoblot analysis. Brain derived neurotrophic factor, which controls the expression of KCC2, was also quantified in the same samples. Addi-tionally, GABA vesicular transporter was included, to estimate GABA synaptic release.

Results: All proteins were detected in the cerebrospinal fluid. NKCC1 and KCC2 are both highly expressed in the first months of life. After 7months of postnatal life, a ten- dency to the predominance of KCC2 was observed. Moreover, we found a statistically significant relationship between the expressions of brain derived neurotrophic factor and KCC2.

Conclusion: These findings might have relevance to the rational treatment of seizures in the first year of life, since GABAA receptor agonists are commonly used in these ages. Moreover, the recognition of an expected normal pattern for neuronal maturity, that can be studied in vivo in severely ill patients, could be helpful in elucidating patho- physiological disturbances underlying early neurodevelopmental disorders.

Key-words: CSF study, cation-chloride cotransporters, early seizures.