News and publications


The below publications include a funding acknowledgement to the project. PREMSTEM researchers are highlighted as bold. Check out our research highlights page to find summaries of selected papers. 

List of publications

Targeting the brain 5-HT7 receptor to prevent hypomyelination in a rodent model of perinatal white matter injuries

Cindy Bokobza, Alice Jacquens, David Guenoun, Blandine Bianco, Anne Galland, Maxime Pispisa, Alexandra Cruz, Manuela Zinni, Valérie Faivre, Anne Roumier, Sophie Lebon, Tania Vitalis, Zsolt Csaba, Tifenn Le Charpentier, Leslie Schwendimann, Pierrette Young-Ten, Vincent Degos, Patricia Monteiro, Pascal Dournaud, Pierre Gressens and Juliette Van Steenwinckel

J Neural Transm. 2022;

Received: 8 July 2022 / Accepted: 19 October 2022 / Published: 6 November 2022

In this article the research team highlights the concept of the HTR7 (5-HT receptor subtype 7) regulating brain inflammation in a context of white matter injury induced by perinatal exposure that models neurodevelopmental disorders associated with prematurity, including memory deficits, anxiety-like-behaviour, and deficits in social interactions. These data open new perspectives for therapy to protect the developing brain from the adverse effects of early immune activation.

The multiple faces of extracellular vesicles released by microglia: Where are we 10 years after?

Martina Gabrielli, Stefano Raffaele, Marta Fumagalli and Claudia Verderio

Front. Cell. Neurosci. 2022; 16:984690; https;//10.3389/fncel.2022.984690

Received: 2 July 2022 / Accepted: 23 August 2022 / Published: 13 September 2022

The review summarises the current knowledge on extracellular vesicles released by microglia, highlighting
their heterogeneous properties and multifaceted effects.

Magnetic Isolation of Microglial Cells from Neonate Mouse for Primary Cell Cultures

Cindy Bokobza, Alice Jacquens, Manuela Zinni, Valérie Faivre, Jennifer Hua, David Guenoun, Caroline
Userovici, Shyamala Mani, Vincent Degos, Pierre Gressens and Juliette Van Steenwinckel

J. Vis. Exp. 2022 (185), e62964;

Published: 25 July 2022

The paper describes a protocol which aims to get as close as possible to the physiological environment of microglia. Besides requiring no serum, the protocol exposes microglia as early as 48 hours after culture to prevent them from losing their physiological faculties.

Download the full paper 

A unique cerebellar pattern of microglia activation in a mouse model of encephalopathy of prematurity

Luisa Klein, Juliette Van Steenwinckel, Bobbi Fleiss, Till Scheuer, Christoph Bührer, Valerie Faivre, Sophie Lemoine, Corinne Blugeon, Leslie Schwendimann, Zsolt Csaba, Cindy Bokobza, Dulcie A. Vousden, Jason P. Lerch, Anthony C. Vernon, Pierre Gressens and Thomas Schmitz

Glia. 2022; 70:1699–1719; 

Received: 16 October 2021 / Revised: 26 April 2022 / Accepted: 29 April 2022 / Published: 27 April 2022

This study used a mouse model of inflammation-induced encephalopathy of prematurity driven by systemic administration of pro-inflammatory IL-1β to look to uncover causes of cerebellar damage, which is associated with impaired motor performance, lower IQ and poor language skills at school ages.

The Impact of Mouse Preterm Birth Induction by RU-486 on Microglial Activation and Subsequent Hypomyelination

Cécile Morin, David Guenoun, Irvin Sautet, Valérie Faivre, Zsolt Csaba, Leslie Schwendimann, Pierrette Young-Ten, Juliette Van Steenwinckel, Pierre Gressens and Cindy Bokobza 

Int. J. Mol. Sci. 202223(9), 4867;

Received: 7 March 2022 / Revised: 21 April 2022 / Accepted: 21 April 2022 / Published: 27 April 2022

This study aimed to elaborate and characterise a new model of induced-PTB and PWMIs by the gestational injection of RU-486 and the perinatal injection of pups with IL-1beta. A RU-486 single subcutaneous (s.c.) injection at embryonic day (E)18.5 induced PTB at E19.5 in pregnant OF1 mice. 

Induction of Mitochondrial Fragmentation and Mitophagy after Neonatal Hypoxia–Ischemia

Syam Nair, Anna-Lena Leverin, Eridan Rocha-Ferreira, Kristina S. Sobotka, Claire Thornton, Carina Mallard and Henrik Hagberg

Cells 2022, 11, 1193;

Received: 20 December 2021 / Accepted: 30 March 2022 / Published: 1 April 2022

This study investigated mitochondrial dynamics (fission, fusion, and mitochondrial autophagy (mitophagy) after HI in vivo in mice and oxygen/glucose deprivation (OGD) in vitro in primary neurons. It also analysed genes/proteins related to mitophagy after HI including PINK1/Parkin, BNIP3/NIX and FUNDC1. The data suggest
that OGD triggers mitochondrial fragmentation and an early increase in mitophagy. 

Targeting microbial metabolites to treat autism

Rochellys Diaz Heijtz, Pierre Gressens and Jonathan R. Swann

Nat Med 28, 448–450 (2022).

Published: 14 February 2022

This article discusses data presented by Campbell et al. and Needham et al. in the study of the microbiota–gut–brain axis as researchers continue to find treatments to improve core symptoms of autism spectrum disorder, such as irritability and anxiety.

Download PDF of Targeting microbial metabolites to treat autism

Peripheral immune cells and perinatal brain injury: a double-edged sword?

Josephine Herz, Ivo Bendix and Ursula Felderhoff-Müser

Pediatr Res 91392–403 (2022);

Received: 15 June 2021 / Revised: 24 August 2021 / Accepted: 14 September 2021 / Published: 8 November 2021

This review focuses on the role of peripheral immune cells and discusses processes involved in neuroinflammation under two frequent perinatal conditions, systemic infection/inflammation associated with encephalopathy of prematurity (EoP) and hypoxia/ischaemia in the context of neonatal encephalopathy and stroke at term. Different immune cell subsets in perinatal brain injury including their infiltration routes were reviewed and critical aspects such as sex differences and maturational stage discussed. Interactions with existing regenerative therapies such as stem cells and also potentials to develop novel immunomodulatory targets were considered.

miR-146b Protects the Perinatal Brain against Microglia-Induced Hypomyelination

Cindy Bokobza, Pooja Joshi, Anne-Laure Schang, Zsolt Csaba, Valérie Faivre, Amélie Montané, Anne Galland, Anouk Benmamar-Badel, Emmanuelle Bosher, Sophie Lebon, Leslie Schwendimann, Shyamala Mani, Pascal Dournaud, Valerie Besson, Bobbi Fleiss, Pierre Gressens and Juliette Van Steenwinckel 

Ann Neurol. (2021);

Received: 7 May 2020 / Accepted: 3 November 2021 / Available online: 5 November 2021

In the preterm newborn, perinatal inflammation mediated by microglia contributes significantly to neurodevelopmental injuries including white matter injury (WMI). This study demonstrates that miR-146b acts as a negative feedback mechanism against inflammatory activation specifically in microglia in a model of WMI, demonstrating that miR mediated therapies may have a future as efficient strategies to protect the developing brain against WMI.

The immune-inflammatory response of oligodendrocytes in a murine model of preterm white matter injury: the role of TLR3 activation

Marta Boccazzi, Juliette Van Steenwinckel, Anne-Laure Schang, Valérie Faivre, Tifenn Le Charpentier, Cindy Bokobza, Zsolt Csaba, Claudia Verderio, Marta Fumagalli, Shyamala Mani and Pierre Gressens

Cell Death Dis 12, 166 (2021);

Received: 2 June 2020 / Revised: 13 December 2020 / Accepted: 3 January 2021 / Available online: 8 February 2021

This study focused on toll-like receptor-3, a protein activated by double-strand RNA, which promotes neuroinflammation. The aim was to better understand its expression and role in oligodendrocytes (one of the last types of cell to form in the brain). The in vivo mouse model mimicked white matter injury occurring in preterm babies.

Therapeutic potential of stem cells for preterm infant brain damage: can we move from the heterogeneity of preclinical and clinical studies to established therapeutics?

Sofia Passera, Marta Boccazzi, Cindy Bokobza, Valerie Faivre, Fabio Mosca, Juliette Van Steenwinckel, Monica Fumagalli, Pierre Gressens and Bobbi Fleiss

Biochemical Pharmacology 2021, 114461;

Received: 10 December 2020 / Revised: 27 January 2021 / Accepted: 2 February 2021 / Available online: 8 February 2021

In this review, the researchers summarise and discuss preclinical and clinical investigations which have studied stem cells as an effective neuroprotectant for perinatal brain injury.

Microglia-Mediated Neurodegeneration in Perinatal Brain Injuries

Bobbi Fleiss, Juliette Van Steenwinckel, Cindy Bokobza, Isabelle K. Shearer, Emily Ross-Munro and Pierre Gressens

Biomolecules 2021, 11(1), 99;

Received: 29 November 2020 / Revised: 8 January 2021 / Accepted: 11 January 2021 / Published: 13 January 2021

This review looks at strategies developed experimentally to modulate microglia and reduce brain injury in babies. It focusses on four causes of perinatal brain injury which occur frequently in both westernised and emerging countries, including EoP and neonatal stroke, and reviews pharmacological approaches as well as novel nanoparticle mediated therapies.

Neuroprotection offered by mesenchymal stem cells in perinatal brain injury: Role of mitochondria, inflammation, and reactive oxygen species

Syam Nair, Eridan Rocha-Ferreira, Bobbi Fleiss, Cora H Nijboer, Pierre Gressens, Carina Mallard and Henrik Hagberg

Journal of Neurochemistry 2021, 2021;158:59–73; 

Received: 15 July 2020 / Revised: 3 December 2020 / Accepted: 3 December 2020 / Published: 12 December 2020

This review summarises the present state, the underlying causes, challenges and possibilities for effective clinical translation of mesenchymal stem cell therapy.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Reduce Neuroinflammation, Promote Neural Cell Proliferation and Improve Oligodendrocyte Maturation in Neonatal Hypoxic-Ischemic Brain Injury

Nicole Kaminski, Christian Köster, Yanis Mouloud, Verena Börger, Ursula Felderhoff-Müser, Ivo Bendix, Bernd Giebel and Josephine Herz

Front. Cell. Neurosci. 2020, 14:601176
Received: 31 August 2020 / Accepted: 19 November 2020 / Published: 10 December 2020
This study investigated the impact of MSC-EVs on neonatal HI-induced brain injury, demonstrating that MSC-EVs mediate anti-inflammatory effects, promote regenerative responses and improve key developmental processes in the injured neonatal brain.

A Model of Germinal Matrix Hemorrhage in Preterm Rat Pups

Masako Jinnai, Gabriella Koning, Gagandeep Singh-Mallah, Andrea Jonsdotter, Anna-Lena Leverin, Pernilla Svedin, Syam Nair, Satoru Takeda, Xiaoyang Wang, Carina Mallard, Carl Joakim Ek, Eridan Rocha-Ferreira and Henrik Hagberg 

Front. Cell. Neurosci. 2020, 14:535320;
Received: 15 February 2020 / Accepted: 5 November 2020 / Published: 3 December 2020
This study aimed to develop and characterise a model of severe germinal matrix hemorrhage (GMH) corresponding to brain maturation in preterm human infants and at an age when the germinal matrix is still present, and to further characterise the pathophysiology of this disease with the hope of assisting novel experimental therapy studies.

Preterm Brain Injury, Antenatal Triggers, and Therapeutics: Timing Is Key

Daan R.M.G. Ophelders, Ruth Gussenhoven, Luise Klein, Reint K. Jellema, Rob J.J. Westerlaken, Matthias C. Hütten, Jeroen Vermeulen, Guido Wassink, Alistair J. Gunn and Tim G.A.M. Wolfs

Cells 20209(8), 1871;
Received: 8 June 2020 / Revised: 31 July 2020 / Accepted: 5 August 2020 / Published: 10 August 2020
This review underlines the importance of employing the right combination of interventions at the right time to support optimal neurodevelopmental outcomes.

Cortical Gray Matter Injury in Encephalopathy of Prematurity: Link to Neurodevelopmental Disorders

Bobbi Fleiss, Pierre Gressens and Helen B. Stolp

Front. Neurol. 2020, 11:575;
Received: 7 April 2020 / Accepted: 19 May 2020 / Published: 14 July 2020