Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke

Abstract Intracerebral haemorrhage (ICH) is the most severe subtype of stroke, with a 2-year mortality of nearly 50% and the greatest rate of disability amongst stroke survivors. Whilst treatment options for ICH remain limited, the condition requires prompt identification and rapid intervention to r...

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Main Authors: Saumya Maheshwari, In Hwa Um, Struan Donachie, Nafeesa Asghar, Karina McDade, Tracey Millar, David J. Harrison, Javier A. Tello
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-83514-0
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author Saumya Maheshwari
In Hwa Um
Struan Donachie
Nafeesa Asghar
Karina McDade
Tracey Millar
David J. Harrison
Javier A. Tello
author_facet Saumya Maheshwari
In Hwa Um
Struan Donachie
Nafeesa Asghar
Karina McDade
Tracey Millar
David J. Harrison
Javier A. Tello
author_sort Saumya Maheshwari
collection DOAJ
description Abstract Intracerebral haemorrhage (ICH) is the most severe subtype of stroke, with a 2-year mortality of nearly 50% and the greatest rate of disability amongst stroke survivors. Whilst treatment options for ICH remain limited, the condition requires prompt identification and rapid intervention to reduce permanent brain damage, with diagnosis traditionally confirmed by CT imaging. Although imaging is excellent at determining the presence of an intracranial bleed, biomarkers may help to identify the type of stroke or when the stroke began. Kisspeptin is a neuropeptide best known for its functions in reproductive biology, but recent preclinical studies have demonstrated that kisspeptins are upregulated in rodent models of haemorrhagic stroke. Here we report for the first time that kisspeptin immunoreactivity is significantly higher in post-mortem human brain tissue after both ICH and ICH associated with cerebral amyloid angiopathy. Machine learning and artificial intelligence-enabled image analysis of multiplexed immunolabeled brain tissues demonstrated that kisspeptin immunoreactivity was higher in cells of the microvasculature (CD105+), but not in neurons or astrocytes when compared to controls. Further spatial analysis indicated that kisspeptin immunoreactivity was concentrated to the region of haemorrhage. These results indicate that following ICH, kisspeptin is significantly higher in the human brain, suggesting expression from local vasculature or recruitment to the haematoma. Further work is required to determine the biological mechanisms underlying kisspeptin elevation within the ICH microenvironment and its potential utility as a novel biomarker or therapeutic target for ICH.
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spelling doaj-art-1399c9a1d03c45268e641fdaa457b1c92025-01-05T12:29:37ZengNature PortfolioScientific Reports2045-23222024-12-0114111110.1038/s41598-024-83514-0Kisspeptin is elevated in the brain after intracerebral haemorrhagic strokeSaumya Maheshwari0In Hwa Um1Struan Donachie2Nafeesa Asghar3Karina McDade4Tracey Millar5David J. Harrison6Javier A. Tello7School of Medicine, University of St AndrewsSchool of Medicine, University of St AndrewsSchool of Medicine, University of St AndrewsSchool of Medicine, University of St AndrewsAcademic Neuropathology, The University of EdinburghAcademic Neuropathology, The University of EdinburghSchool of Medicine, University of St AndrewsSchool of Medicine, University of St AndrewsAbstract Intracerebral haemorrhage (ICH) is the most severe subtype of stroke, with a 2-year mortality of nearly 50% and the greatest rate of disability amongst stroke survivors. Whilst treatment options for ICH remain limited, the condition requires prompt identification and rapid intervention to reduce permanent brain damage, with diagnosis traditionally confirmed by CT imaging. Although imaging is excellent at determining the presence of an intracranial bleed, biomarkers may help to identify the type of stroke or when the stroke began. Kisspeptin is a neuropeptide best known for its functions in reproductive biology, but recent preclinical studies have demonstrated that kisspeptins are upregulated in rodent models of haemorrhagic stroke. Here we report for the first time that kisspeptin immunoreactivity is significantly higher in post-mortem human brain tissue after both ICH and ICH associated with cerebral amyloid angiopathy. Machine learning and artificial intelligence-enabled image analysis of multiplexed immunolabeled brain tissues demonstrated that kisspeptin immunoreactivity was higher in cells of the microvasculature (CD105+), but not in neurons or astrocytes when compared to controls. Further spatial analysis indicated that kisspeptin immunoreactivity was concentrated to the region of haemorrhage. These results indicate that following ICH, kisspeptin is significantly higher in the human brain, suggesting expression from local vasculature or recruitment to the haematoma. Further work is required to determine the biological mechanisms underlying kisspeptin elevation within the ICH microenvironment and its potential utility as a novel biomarker or therapeutic target for ICH.https://doi.org/10.1038/s41598-024-83514-0StrokeIntracerebral haemorrhageICHKisspeptinBiomarkerCerebral amyloid angiopathy
spellingShingle Saumya Maheshwari
In Hwa Um
Struan Donachie
Nafeesa Asghar
Karina McDade
Tracey Millar
David J. Harrison
Javier A. Tello
Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke
Scientific Reports
Stroke
Intracerebral haemorrhage
ICH
Kisspeptin
Biomarker
Cerebral amyloid angiopathy
title Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke
title_full Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke
title_fullStr Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke
title_full_unstemmed Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke
title_short Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke
title_sort kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke
topic Stroke
Intracerebral haemorrhage
ICH
Kisspeptin
Biomarker
Cerebral amyloid angiopathy
url https://doi.org/10.1038/s41598-024-83514-0
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