ePoster

Cuproptosis, copper homeostasis, and management in intracerebral haemorrhage (ICH)

Tsz Ching Alexia Ng, Cuiting Zhang, Karrie Mei Yee Kiang, Gilberto Ka Kit Leung
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Tsz Ching Alexia Ng, Cuiting Zhang, Karrie Mei Yee Kiang, Gilberto Ka Kit Leung

Abstract

Intracerebral haemorrhage (ICH) is a subtype of stroke, characterised by bleeding into brainparenchyma. In 2022, studies discovered a novel mechanism of cell death, cuproptosis, referring to copper-induced cell death. In ICH, disruption of blood-brain barrier followed by infiltration of copper from plasma into brain, results in copper overload and cuproptosis. Oligomerization of Dihydrolipoamide S-Acetyltransferase (DLAT) has been identified as a hallmark of cuproptosis. We aim to study whether ICH would induce cuproptosis as a result of DLAT accumulation. ICH was induced in C57BL/6 mice by collagenase injection into right striatum of brain, while sham surgery was performed as control without collagenase injection. Copper levels in hematoma and peri-hematoma region were measured using colorimetric copper assay kit. Western blot was performed to detect DLAT oligomer. Copper chelator tetrathiomolybdate was used to eliminate copper accumulation, neurological function was assessed following treatment. Expression levels of SLC31A1, a copper transporter, in peri-hematoma region were measured using quantitative polymerase chain reaction (qPCR). Copper level in brain with ICH is higher than that in sham. Hallmark of cuproptosis is detected in brain with ICH. Modified neurological severity score and rotarod test suggest improved functional outcome in mice treated with tetrathiomolybdate. Lower expression levels of SLC31A1 are detected in brain with ICH. Cuproptosis contributes to cell death in ICH. Inhibition of cuproptosis by copper chelation can be used as a novel therapeutic strategy of ICH.

Unique ID: fens-24/cuproptosis-copper-homeostasis-management-eef5fbdb