A Claim For Caution in the Use of Promising Bumetanide to Treat Neonatal Seizures

Chabwine, Joëlle Nsimire; Eijnden, Serge Vanden

doi:10.1177/0883073811401395

Cited by 10 publications

(3 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, due to its ability to inhibit the brain-specific transporter NKCC1, bumetanide has been proposed as a promising candidate to treat brain diseases 46 , based on studies in animal models 12, 34, 46 and recent clinical trials 46-48 . However, the use of this drug in neonates has been partially questioned 10, 49-50 due to the key role played by depolarizing GABA during early development 8 . Our data similarly suggest possible long-term consequences of NKCC1 inhibition during early development.…”

Section: Discussionmentioning

confidence: 99%

Early depolarizing GABA controls critical-period plasticity in the rat visual cortex

et al. 2014

View full text Add to dashboard Cite

SUMMARYHyperpolarizing and inhibitory GABA regulates “critical periods” for plasticity in sensory cortices. Here, we examine the role of early, depolarizing GABA in controlling plasticity mechanisms. We report that brief interference with depolarizing GABA during early development prolonged critical period plasticity in visual cortical circuits, without affecting overall development of the visual system. The effects on plasticity were accompanied by dampened inhibitory neurotransmission, down-regulation of BDNF expression, and reduced density of extracellular matrix-perineuronal nets. Early interference with depolarizing GABA decreased perinatal BDNF signaling, and pharmacological increase of BDNF signaling during GABA interference rescued the effects on plasticity and its regulators later in life. We conclude that depolarizing GABA exerts a long-lasting, selective modulation of plasticity of cortical circuits by a strong crosstalk with BDNF.

show abstract

Section: Discussionmentioning

confidence: 99%

Early depolarizing GABA controls critical-period plasticity in the rat visual cortex

et al. 2014

View full text Add to dashboard Cite

show abstract

“…As mentioned above, NKCC1 has an age-dependent expression in SNR and hippocampus. While the effects of bumetanide on seizures need to be interpreted cautiously (Vanhatalo et al, 2009; Chabwine and Vanden Eijnden, 2011), it would be worth testing also the effects of loop diuretic drugs into the SNR to assess their potential age- and sex-related role in SNR-mediated epilepsy modulation.…”

Section: Discussionmentioning

confidence: 99%

Sex dimorphism in seizure-controlling networks

Giorgi

Galanopoulou²,

Moshé

2014

Neurobiology of Disease

View full text Add to dashboard Cite

Males and females show a different predisposition to certain types of seizures in clinical studies. Animal studies have provided growing evidence for sexual dimorphism of certain brain regions, including those that control seizures. Seizures are modulated by networks involving subcortical structures, including thalamus, reticular formation nuclei, and structures belonging to the basal ganglia. In animal models, the substantia nigra pars reticulata (SNR) is the best studied of these areas, given its relevant role in the expression and control of seizures throughout development in the rat. Studies with bilateral infusions of the GABAA receptor agonist muscimol have identified distinct roles of the anterior or posterior rat SNR in flurothyl seizure control, that follow sex-specific maturational patterns during development. These studies indicate that (a) the regional functional compartmentalization of the SNR appears only after the third week of life, (b) only the male SNR exhibits muscimol-sensitive proconvulsant effects which, in older animals, is confined to the posterior SNR, and (c) the expression of the muscimol-sensitive anticonvulsant effects become apparent earlier in females than in males. The first three postnatal days are crucial in determining the expression of the muscimol-sensitive proconvulsant effects of the immature male SNR, depending on the gonadal hormone setting. Activation of the androgen receptors during this early period seems to be important for the formation of this proconvulsant SNR region. We describe molecular/anatomical candidates underlying these age- and sex-related differences, as derived from in vitro and in vivo experiments, as well as by [14C]2-deoxyglucose autoradiography. These involve sex-specific patterns in the developmental changes in the structure or physiology or GABAA receptors or of other subcortical structures (e.g., locus coeruleus, hippocampus) that may affect the function of seizure-controlling networks.

show abstract

“…A single clinical study showed reduction in seizure frequency and duration following bumetanide treatment [90]. Though promising as an add-on agent for neonatal seizures, the potential for adverse effects such as ototoxicity, and partial central nervous system bioavailability may ultimately limit the utility of bumetanide [91]. …”

Section: Pharmacologic Strategiesmentioning

confidence: 99%

Neonatal Seizures

Glass

2014

Clinics in Perinatology

View full text Add to dashboard Cite

Synopsis Seizures occur in approximately 1–5 per 1,000 live births, and are among the most common neurologic conditions managed by a neonatal neurocritical care service. There are several, age-specific factors that are particular to the developing brain, which influence excitability and seizure generation, response to medications, and impact of seizures on brain structure and function. Neonatal seizures are often associated with serious underlying brain injury such as hypoxia-ischemia, stroke or hemorrhage. Conventional, prolonged, continuous video-electroencephalogram (cEEG) is the gold standard for detecting seizures, whereas amplitude-integrated EEG (aEEG) is a convenient and useful bedside tool. Evaluation of neonatal seizures involves a thorough search for the etiology of the seizures, and includes detailed clinical history, routine chemistries, neuroimaging (and preferably magnetic resonance imaging, MRI), and specialized testing such as screening for inborn errors of metabolism if no structural cause is identified and seizures persist after correction of transient metabolic deficits. Expert opinion supports rapid medical treatment to abolish electrographic seizures, however the relative risk versus benefit for aggressive medical treatment of neonatal seizures is not known. While there is increasing evidence to support a harmful effect of seizures on the developing brain, there is also evidence that commonly used medications are potentially neurotoxic in animal models. Newer agents appear less harmful, but data are lacking regarding optimal dosing and efficacy.

show abstract

A Claim For Caution in the Use of Promising Bumetanide to Treat Neonatal Seizures

Cited by 10 publications

References 11 publications

Early depolarizing GABA controls critical-period plasticity in the rat visual cortex

Early depolarizing GABA controls critical-period plasticity in the rat visual cortex

Sex dimorphism in seizure-controlling networks

Neonatal Seizures

Contact Info

Product

Resources

About