Home > Teams > Metabolic and Cardiovascular Diseases > HCEMM- USZ Cerebral Blood Flow and Metabolism Research Group
Group Leader: Eszter Farkas PhD, DSc
The evolution of cerebral edema is a life-threatening condition, yet our concept of how brain edema develops is incomplete, and treatment options remain limited. The current project addresses two challenges: (i) We will develop a new strategy for timely, accurate diagnosis to predict cerebral edema formation; and (ii) will offer novel, targeted, non-invasive and personalized therapy for the effective alleviation of brain edema formation. Furthermore, we posit that astrocyte swelling – as seen in a preliminary study of ours – and reactive astrogliosis typical of cerebral ischemia are directly and causally linked, and mediate edema-related neuronal injury. We will establish preclinical rodent models of cerebral ischemia and associated edema formation, and will monitor intracranial pressure with a telemetry based wireless system in freely moving animals for a clinically relevant time window. We will monitor astrocyte swelling at chosen time points with fluorescent astrocyte markers and multi-photon microscopy, and identify the reactive phenotype of astrocytes with immunolabeling and confocal microscopy. Led by our hypothesis that the serum level of endothelin 1 (ET-1) and natriuretic peptides – both produced by reactive astrocytes – are potential biomarkers to reflect cerebral edema formation, we will measure the blood concentration of ET-1 and natriuretic peptide repeatedly with ELISA, and match the data with intracranial pressure and the volume of the ultimate brain infarction. Because ET-1 is suggested to initiate astrogliosis by the activation of astrocytic endothelin B (ETB) receptors, we will explore this mechanism in conditional astrocytic ETB receptor knock-out ischemic mice. We will examine the potential of pharmacological ETB receptor antagonism, as a pertinent means to break the ET‑1/ETB receptor signaling cycle. This is then expected to suppress astrocyte reactivity, prevent the formation of cerebral edema, and ultimately, achieve neuroprotection.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 739593. HCEMM supported by EU Programme: H2020-EU.4.a. – Teaming of excellent research institutions and low performing RDI regions. Project starting date was 1 April 2017.