Is It Safe to Use a Diuretic to Treat Seizures Early in Development
Yehezkel Ben-Ari,Roman Tyzio +1 more
TLDR
The importance of separating intrauterine from postnatal effects of bumetanide in normal versus pathologic neurons is considered, because reduction of (Cl−)i also alleviates a major source of excitation in developing neurons, upon which GABA exerts a trophic action.Abstract:
There has been considerable interest in using bumetanide, a diuretic chloride importer NKCC1 antagonist, to reduce intracellular chloride ([Cl−]i) in epileptic neurons, thereby shifting the polarity of GABA from excitatory to inhibitory and ameliorating the actions of GABA-acting antiepileptic drugs. However, a recent study raises the important issue of potential deleterious actions of bumetanide on immature neurons, because reduction of (Cl−)i also alleviates a major source of excitation in developing neurons, upon which GABA exerts a trophic action. This review considers the importance of separating intrauterine from postnatal effects of bumetanide in normal versus pathologic neurons.read more
Citations
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Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments.
TL;DR: This review shows that the antiepileptic effects of loop diuretics described in the pertinent literature are based on widely heterogeneous mechanisms ranging from actions on both neuronal NKCC1 and KCC2 to modulation of the brain extracellular volume fraction.
Journal ArticleDOI
The GABA excitatory/inhibitory developmental sequence: A personal journey
TL;DR: A personal history of how an unexpected observation led to novel concepts in developmental neurobiology and putative treatments of autism and other developmental disorders is presented.
Neuroscience forefront review the gaba excitatory/inhibitory developmental sequence: a personal journey
TL;DR: In this article, the authors present a personal account of how an unexpected observation led to novel concepts in developmental neurobiology and putative treatments of autism and other developmental disorders, and illustrate why we often fail to compre- hend the implications of our own observations.
Journal ArticleDOI
Finding a better drug for epilepsy: Antiepileptogenesis targets
Katja Kobow,Stéphane Auvin,Frances E. Jensen,Wolfgang Löscher,Istvan Mody,Heidrun Potschka,David A. Prince,Alejandra Sierra,Michele Simonato,Asla Pitkänen,Astrid Nehlig,Jong M. Rho +11 more
TL;DR: Novel antiepileptogenesis targets that were critically discussed at the XIth Workshop on the Neurobiology of Epilepsy (WONOEP XI) meeting in Grottaferrata, Italy are summarized.
Journal ArticleDOI
Expression of GABA receptor subunits in the hippocampus and thalamus after experimental traumatic brain injury
TL;DR: In this paper, the expression of major GABAA receptor subunit mRNAs (α1, α2, α5, β2, β3, γ2 and δ) was found to be downregulated in the granule cell layer (GCL) and in the CA3 pyramidal cells.
References
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Journal ArticleDOI
Excitatory actions of gaba during development: the nature of the nurture.
TL;DR: This work proposes that GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions, and provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation.
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The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation.
Claudio Rivera,Juha Voipio,John A. Payne,Eva Ruusuvuori,Hannele Lahtinen,Karri Lamsa,Ulla Pirvola,Mart Saarma,Kai Kaila +8 more
TL;DR: It is shown that, in pyramidal neurons of the rat hippocampus, the ontogenetic change in GABAA-mediated responses from depolarizing to hyperpolarizing is coupled to a developmental induction of the expression of the neuronal Cl−-extruding K+/Cl − co-transporter, KCC2 (ref. 7).
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GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations
TL;DR: It is suggested that an evolutionary preserved role for excitatory GABA in immature cells provides an important mechanism in the formation of synapses and activity in neuronal networks.
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Is there more to gaba than synaptic inhibition
TL;DR: The unique features of the early-appearing GABA signalling systems might help to explain how GABA acts as a developmental signal in the immature brain.
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On the origin of interictal activity in human temporal lobe epilepsy in vitro.
TL;DR: A spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy was described, similar to interictal discharges of patient electroencephalograms.