Pericyte disconnection as the culprit for worse stroke outcome upon (ageing-induced) endothelial Prdm16 loss: Thalidomide to the rescue.
Description: Globally, ischaemic stroke is a leading cause of death and permanent disability and is caused by cerebral artery occlusion. As ischaemic stroke is a disease of ageing, its prevalence and socioeconomic burden will continue to rise, highlighting the urgent need for effective interventions. Restoring cerebral blood flow by functionalising collateral arteri(ol)es and preserving the integrity of blood-brain barrier capillaries is the most desirable strategy to salvage ischaemic brain tissue. Recently, I found that Prdm16 in endothelial cells (ECs) plays a protective role during stroke by maintaining both arteriolar and capillary function. However, its expression in the cerebral vasculature declines upon ageing. Targeting Prdm16 or its downstream mediators may therefore be of great interest to ameliorate stroke outcome, especially within the aged brain. The mechanisms of Prdm16’s downstream actions upon stroke remain largely unknown but I have compiled evidence that points towards a role in stabilising EC-pericyte (PC) interactions in cerebral arterioles and capillaries. Here, I aim to investigate whether improving EC-PC interaction via thalidomide can improve stroke outcome in genetically- or ageing-induced endothelial Prdm16 loss. Moreover, I will unveil the putative mode of action of thalidomide treatment in different cerebral vascular compartments during ischaemic stroke. Altogether, this project will lead to the identification of new treatment strategies for stroke patients.
Funder: Fonds Wetenschappelijk Onderzoek
Funding type: fellowship
Funder scheme: FWO senior postdoctoral fellowship
Start date: 2026-10-01
End date: 2029-09-30
Investigator: Hannelore Kemps
Institution: KULeuven
Funded outputs count: 0
Funder award ID: 1258527N
OpenAlex ID: G6736061583