Publications by authors named "T T Fiacco"

During brain disease, astrocytes can reprogram into a reactive state that alters many of their functions. Here, we present a protocol for studying neuroinflammation and reactive astrogliosis in mice using lipopolysaccharide (LPS) from E. coli.

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Multiple subfields of neuroscience research are beginning to incorporate astrocytes into current frameworks of understanding overall brain physiology, neuronal circuitry, and disease etiology that underlie sleep and sleep-related disorders. Astrocytes have emerged as a dynamic regulator of neuronal activity through control of extracellular space (ECS) volume and composition, both of which can vary dramatically during different levels of sleep and arousal. Astrocytes are also an attractive target of sleep research due to their prominent role in the glymphatic system, a method by which toxic metabolites generated during wakefulness are cleared away.

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Article Synopsis
  • Volume-regulated anion channels (VRACs) help cells manage their volume by allowing the outflow of anions and organic molecules, such as glutamate, especially during conditions like swelling, which often happens during seizures.
  • The study investigated the expression of the VRAC subunit LRRC8A in mesial temporal lobe epilepsy (MTLE) using a specific experimental model, finding that LRRC8A was significantly upregulated in the hippocampus at different time points after inducing epilepsy.
  • The increased levels of LRRC8A in astrocytes and neurons, along with changes in associated glutamate metabolism enzymes, suggest that dysregulated VRAC function may contribute to the development of epilepsy by affecting glutamate dynamics in
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Astrocytes are vital support cells that ensure proper brain function. In brain disease, astrocytes reprogram into a reactive state that alters many of their cellular roles. A long-standing question in the field is whether downregulation of reactive astrocyte (RA) markers during resolution of inflammation is because these astrocytes revert back to a non-reactive state or die and are replaced.

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Volume Regulated Anion Channels (VRAC) are critical contributors to cell volume homeostasis and are expressed ubiquitously in all vertebrate cells. VRAC sense increases in cell volume, and act to return cells to baseline volume in a process known as regulatory volume decrease (RVD) through the efflux of anions and organic osmolytes. This review will highlight seminal studies that elucidated the role of VRAC in RVD, their characteristics as a function of subunit specificity, and their clinical relevance in physiology and pathology.

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