Project Details
Projekt
Meningeal immune cell priming for stroke recovery
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular and Cellular Neurology and Neuropathology
Molecular and Cellular Neurology and Neuropathology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 405358801
Neuroinflammatory mechanisms contribute substantially to the pathophysiology of acute brain injuries including stroke. Key components of neuroinflammation in stroke are the activation of resident microglial cells as well as the invasion of circulating leukocytes into the brain. Recruitment of peripheral immune cells is not limited to the brain parenchyma in stroke but also occurs in the choroid plexus and meninges – the central nervous system-associated border tissues and this contributes to infarct development. In fact, unlike the brain parenchyma, the meninges contain various immune populations in homeostatic conditions that are derived from the systemic circulation and locally from the skull bone marrow niches providing efficient immunosurveillance. These recent findings emphasize a possible role of immune cells at these blood-brain interfaces participating actively in the post-stroke neuroinflammatory response. Therefore, the overall objective of this new project is to understand the involvement of meningeal immune cells in regulating the neuroinflammatory response in post-stroke recovery. For this, we will characterize the stroke-mediated phenotypic changes of meningeal immune cells (Aim 1), investigate meningeal immune cell priming and trafficking into the brain parenchyma long-term after stroke (Aim 2) and modulate meningeal immune cell function to evaluate its effect on long-term brain plasticity and functional recovery (Aim 3). Specifically, meningeal immune cell homeostasis and polarization will be analyzed by single nuclei transcriptomic analysis in mice and stroke patients. Immune cell migration from the meninges to the brain parenchyma will be investigated by using photoconversion of meningeal immune cells in mouse models to specifically track their trafficking behavior. Importantly, the role of meningeal immune cells in neuroplasticity mechanisms and post-stroke recovery will be addressed by pharmacological modulators in the meninges. By combining the unique expertise of the three PIs, this study will thus address a key question not yet addressed in the “ImmunoStroke FOR2879” research unit – the contribution of meningeal immune cells in stroke recovery – which is of direct clinical relevance.
DFG Programme
Research Units
