Publications by authors named "Hailey Worstman"
Background: A variety of molecular targets for volatile anesthetics have been suggested, including the anesthetic-sensitive potassium leak channel, TREK-1. Knockout of TREK-1 is reported to render mice resistant to volatile anesthetics, making TREK-1 channels compelling targets for anesthetic action. Spinal cord slices from mice, either wild type or an anesthetic- hypersensitive mutant, Ndufs4, display an isoflurane-induced outward potassium leak that correlates with their minimum alveolar concentrations and is blocked by norfluoxetine.
View Article and Find Full Text PDFBackground: If anaesthetics cause permanent cognitive deficits in some children, the implications are enormous, but the molecular causes of anaesthetic-induced neurotoxicity, and consequently possible therapies, are still debated. Anaesthetic exposure early in development can be neurotoxic in the invertebrate Caenorhabditis elegans causing endoplasmic reticulum (ER) stress and defects in chemotaxis during adulthood. We screened this model organism for compounds that alleviated neurotoxicity, and then tested these candidates for efficacy in mice.
View Article and Find Full Text PDFArticle Synopsis
- Volatile anesthetics (VAs) are commonly used in medical settings, but their exact mechanisms and potential impacts, particularly on neonatal brain development, are not fully understood.
- In neonatal mice, VAs quickly deplete a key metabolic compound, β-hydroxybutyrate (β-HB), at lower concentrations than needed for anesthesia, while adults show no such depletion.
- The depletion of β-HB in neonates is linked to metabolic processes involving citrate accumulation and changes in fatty acid metabolism, highlighting significant differences in metabolic responses between neonates and adults.
Background: Ndufs4 knockout (KO) mice are defective in mitochondrial complex I function and hypersensitive to inhibition of spinal cord-mediated response to noxious stimuli by volatile anesthetics. It was hypothesized that, compared to wild-type, synaptic or intrinsic neuronal function is hypersensitive to isoflurane in spinal cord slices from knockout mice.
Methods: Neurons from slices of the vestibular nucleus, central medial thalamus, and spinal cord from wild-type and the global Ndufs4 knockout were patch clamped.