Our team is interested in how to regulate this perivascular space as well as the cells composing it, with the aim of maintaining normal brain functions.

Neurons are the cells responsible for brain functions, and inevitably produce metabolic waste that can be toxic. However, the brain, unlike other organs, does not contain lymphatic vessels necessary for the proper clearance of waste debris. The brain therefore had to adapt anatomically to this constraint in order to free itself from its waste and maintain its normal functions.

It has been demonstrated that cerebrospinal fluid (CSF) can penetrate the brain parenchyma and then exit the brain carrying the accumulated waste. We recently showed that resident macrophages in the CSF surrounding blood vessels, so-called perivascular macrophages, can regulate the movement of blood vessels that are essential for cerebrospinal fluid flow into the brain. Dysfunction of these macrophages leads to dysfunction of the perivascular space and consequently to poor clearance of waste. Our team is interested in how to regulate this perivascular space as well as the cells composing it, with the aim of maintaining normal brain functions.

We will first study the origin/development of perivascular spaces in vivo and using spatial transcriptomics. We will study the interactions between perivascular macrophages and other cells residing in the perivascular space using various genetic mouse models and in vitro approaches. Finally, we will study the dysfunction of perivascular spaces in vivo and with single cell RNA sequencing.

5 Major publications

1. Parenchymal border macrophages regulate the flow dynamics of the cerebrospinal fluid. Drieu A, Du S, Storck SE, Rustenhoven J, Papadopoulos Z, Dykstra T, Zhong F, Kim K, Blackburn S, Mamuladze T, Harari O, Karch CM, Bateman RJ, Perrin R, Farlow M, Chhtawal J, DIAN, Hu S, Randolph GJ, Smirnov I, Kipnis J. Nature. 2022 Nov;611(7936):585-593. doi: 10.1038/s41586-022-05397-3.

2. Waste clearance shapes aging brain health. Jiang-Xie LF, Drieu A, Kipnis J. Neuron. 2024 Oct 8: S0896-6273(24)00687-1. doi: 10.1016/j.neuron.2024.09.017.

3. Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance. Jiang-Xie LF, Drieu A, Bhasiin K, Quintero D, Smirnov I, Kipnis J. Nature. 2024 Mar;627(8002):157-164. doi: 10.1038/s41586-024-07108-6.

4. Identification of direct connections between the dura and the brain. Smyth LCD, Xu D, Okar SV, Dykstra T, Rustenhoven J, Papadopoulos Z, Bhasiin K, Kim MW, Drieu A, Mamuladze T, Blackburn S, Gu X, Gaitan MI, Nair G, Storck SE, Du S, White MA, Bayguinov P, Smirnov I, Dikranian K, Reich D, Kipnis J. Nature. 2024 Mar;627(8002):165-173. doi: 10.1038/s41586-023-06993-7.

4. Functional characterization of the dural sinuses as a neuroimmune interface. Rustenhoven J, Drieu A, Mamuladze T, de Lima KA, Dykstra T, Wall M, Papadopoulos Z, Kanamori M, Salvador AF, Baker W, Lemieux M, Da Mesquita S, Cugurra A, Fitzpatrick J, Sviben S, Kossina R, Bayguinov P, Townsend RR, Zhang Q, Erdmann-Gilmore P, Smirnov I, Lopes MB, Herz J, Kipnis J.  Cell. 2021 Feb 18;184(4):1000-1016.e27. doi: 10.1016/j.cell.2020.12.040.

Address :
INSERM U1266, 102-108 rue de la santé, 75014, Paris

Team leader :
Drieu Antoine
Name of co-team leader :

Administrative Contact Name :


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Key words : #Cerveau, #méninges, #espaces périvasculaires, #système immunitaire, #liquide cérébrospinal #Brain, #meninges, #perivascular spaces,#immune system, #cerebrospinal fluid