Nanna MacAulay

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The mammalian brain consists of a large quantity of water which is continuously shifted between the circulating blood and the brain parenchyma as well as between different compartments and cellular structures within the brain tissue. We presume that the transport of water between these different compartments is under tight control since a disturbance in the cerebral water homeostasis (with associated changes in ion concentrations) may lead to neuronal dysfunction, hydrocephalus, and/or brain edema. However, our incomplete knowledge of the molecular mechanisms responsible for the maintenance of cerebral water transport and their regulation currently prevents us from gaining a full understanding of this intricate and crucial (patho)physiological issue. With this lack of identification of the implicated transport mechanisms and their dysregulation in pathology, pharmacological therapy is essentially unavailable for potentially life-threatening conditions involving brain water accumulation, i.e. hydrocephalus, brain edema, acute liver failure, idiopathic intracranial hypertension, etc.

The focus of our laboratory is to elucidate the molecular mechanisms underlying water and ion homeostasis in the mammalian brain under both physiological and pathophysiological conditions. We investigate the transport mechanisms underlying cerebrospinal fluid secretion, brain extracellular fluid generation, activity-dependent glial cell swelling during stimulus-evoked K⁺ management, and dendritic beading observed during spreading depolarization. Our technical approach spans from molecular and biophysical properties of water transport proteins (including aquaporins and cotransporters) to their regulation at the cellular level and their integral function in acutely prepared brain slices and rodent in vivo models.