Unravelling the role of cell-specific interleukin-1B during cerebrovascular inflammation after stroke
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
Interleukin-1 (IL-1) drives inflammation after stroke, contributing to brain damage and poorer outcome. Blocking IL-1 actions with the IL-1 receptor antagonist (IL-1Ra) is beneficial in pre-clinical stroke models, and studies in stroke patients show that IL-1Ra is safe and may improve clinical outcomes. Importantly, IL-1 is expressed as two isoforms, IL-1 alpha (IL-1a) and IL-1 beta (IL-1B), but the specific function of each ligand in stroke is completely unknown. We have recently generated new conditional IL-1 genetic mouse models to precisely identify the relative contribution of IL-1a and IL-1B during stroke. This can be achieved by selectively deleting each of those IL-1 members in key brain cells that are known to contribute to inflammation after stroke (primarily endothelial cells, microglia and neurons), and to assess the effect of gene deletion on cerebrovascular inflammation and stroke outcome. Our recent preliminary experiments demonstrated that IL-1B (main driver of neuroinflammation after stroke) is expressed in a subset of microglia and infiltrating neutrophils after stroke but the function of microglial- and neutrophil-derived IL-1B in stroke is completely unknown. The aim of the project is to further explore the precise pathophysiological function of IL-1B in stroke by analysing the effect of selective deletion of IL-1B in microglia and neutrophils on stroke outcome, mechanisms of cerebrovascular inflammation, long term vascular repair and functional recovery, using a combination of in vitro and in vivo models of cerebral ischaemia, as well as a large array of powerful molecular, cellular and imaging analytical techniques. The ultimate aim of the project is to provide a better insight into the potential neuroprotective and neuroreparative role of IL-1B during post stroke inflammation for better therapeutic interventions.
Organisations
People |
ORCID iD |
Emmanuel Pinteaux (Primary Supervisor) | |
Margarida Baptista (Student) |
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
MR/W007428/1 | 01/10/2022 | 30/09/2028 | |||
2896596 | Studentship | MR/W007428/1 | 01/10/2023 | 30/09/2027 | Margarida Baptista |