Kisspeptin is elevated in the brain after intracerebral haemorrhagic stroke

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.