Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by progressive degeneration of both upper and lower motor neurons, resulting in paralysis eventually leads to death from respiratory failure typically within 3 5 years symptom onset. The aim this work was predict the pharmacokinetics identify unique protein targets that are associated with potential ...

The persistent sodium current (I(NaP)) is known to play a role in rhythm generation in different systems. Here, we investigated its contribution to locomotor pattern generation in the neonatal rat spinal cord. The locomotor network is mainly located in the ventromedial gray matter of upper lumbar segments. By means of whole cell recordings in slices, we characterized membrane and I(NaP) biophys...

We read with great interest the paper by Fornai et al. (1) on delayed progression of amyotrophic lateral sclerosis (ALS) with lithium. In this study the results of a small randomized clinical trial were also reported. Sixteen patients (4 of whom had the bulbar form of ALS) were randomly selected to receive riluzole plus lithium, and 28 (7 of whom had the bulbar form of ALS) received riluzole on...

The persistent (i.e., slowly inactivating) fraction of the Na current (I(Na,P)) regulates excitability of CNS neurons. In isolated rat suprachiasmatic nucleus (SCN) neurons with a ramp-type voltage-clamp protocol, we have studied the properties of a robust current that has the general properties of I(Na,P) but exhibits a slow inactivation (I(Na,S)). The time dependence of the development of the...

introduction: purkinje cell (pc) output displays a complex firing pattern consisting of high frequency sodium spikes and low frequency calcium spikes, and disruption in this firing behavior may contribute to cerebellar ataxia. riluzole, neuroprotective agent, has been demonstrated to have neuroprotective effects in cerebellar ataxia. here, the spectral analysis of pcs firing in control, 3-acety...

Systemic hypoxia in mammals is sensed and transduced by the carotid body into increased action potential (AP) frequency on the sinus nerve, resulting in increased ventilation. The mechanism of hypoxia transduction is not resolved, but previous work suggested that fast Na(+) channels play an important role in determining the rate and timing of APs (Donnelly, DF, Panisello JM, and Boggs D. J Phys...

OBJECTIVE Bromocriptine mesylate (BRC), a dopamine D2 receptor agonist has been shown to confer neuroprotection, sustained motor function and slowed disease progression in mouse models of amyotrophic lateral sclerosis (ALS) Here we report a first in human trial in ALS. DESIGN A multicenter, Riluzole add-on, randomized, double-blind, placebo controlled 102-week extension BRC clinical trial. ...

This retrospective study aimed to investigate the clinical features associated with deteriorated swallow in amyotrophic lateral sclerosis (ALS) patients with spinal and bulbar onset, describe the modification of diet and liquid intake, and assess the impact of dysphagia on the use of riluzole. One hundred forty-five patients were observed periodically every 3-6 months. They underwent routinely ...

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BACKGROUND Severe spinal muscular atrophy (SMA) (Werdnig-Hoffmann disease, acute SMA, and SMA I) is a disease of the motor neuron characterized by onset before 6 months of age, failure ever to achieve sitting without support, and a life expectancy of 2 years or less. There is no known treatment for SMA, and, until recently, no therapeutic trials have been attempted. There is reason to believe t...