Chemogenetic activation of oxytocinergic neurons modulates acute neuroinflammation and improves brain development after pediatric traumatic brain injury

Article Article scientifique Article Chemogenetic activation of oxytocinergic neurons modulates acute neuroinflammation and improves brain development after pediatric traumatic brain injury eng 2026-01-16 2026-03 author Knoop Marit Department of Child Growth and Development, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland. 957155 author Trak Ece Department of Child Growth and Development, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland. 988683 author Possovre Marie-Laure Department of Child Growth and Development, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland. 962311 author Van De Looij Yohan Department of Child Growth and Development, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland; Center for Biomedical Imaging (CIBM), Animal Imaging Technology Section, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. 652102 author Schirmbeck Gabriel Department of Child Growth and Development, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland. 415462 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Ceyzeriat Kelly Center for Biomedical Imaging (CIBM), University of Geneva 1205 Geneva, Switzerland. 910236 Centre d'imagerie bio-médicale (CIBM) author Pitetti Jean-Luc Laboratory animal facility, University of Geneva 1205 Geneva, Switzerland. 133686 Animalerie (ANIMO) author Farias Sanches Eduardo Department of Child Growth and Development, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland. 842583 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Musardo Stefano Department of Basic Neuroscience, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland. 862798 author Millet Philippe 0000-0002-5803-0478 Department of Psychiatry, University Hospital of Geneva and University of Geneva 1205 Geneva, Switzerland. 668343 Département de psychiatrie (PSYAT) author Tsartsalis Stergios 0000-0002-6565-6313 Department of Psychiatry, University Hospital of Geneva and University of Geneva 1205 Geneva, Switzerland. 782369 Département de psychiatrie (PSYAT) author Tournier Benjamin Department of Psychiatry, University Hospital of Geneva and University of Geneva 1205 Geneva, Switzerland. 705309 Département de psychiatrie (PSYAT) author Bellone Camilla 0000-0002-6774-6275 Department of Basic Neuroscience, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland. 559161 Département de neurosciences fondamentales (NEUFO) author Sizonenko Stéphane 0000-0003-0093-8747 Department of Child Growth and Development, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland. 24332 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Jacquens Alice Faculty of Medicine, Université Paris Cité, Inserm, NeuroDiderot 75019 Paris, France; Sorbonne University, GRC 29, AP-HP, DMU DREAM, Department of Anaesthesiology and Critical Care Medicine, Pitié-Salpêtrière Hospital, 75013 Paris, France. 975633 author Baud Olivier Department of Child Growth and Development, Faculty of Medicine, University of Geneva 1205 Geneva, Switzerland; Faculty of Medicine, Université Paris Cité, Inserm, NeuroDiderot 75019 Paris, France; Obstetric, Perinatal, Paediatric and Life Course Epidemiology Team (OPPaLE), Center for Research in Epidemiology and StatisticS (CRESS), Alimentation Et L'Environnement (INRAe), Institut National Pour La Santé Et La Recherche Médicale (INSERM, French Institute for Health and Medical ResearchInstitut National de Recherche Pour L'Agriculture, Paris Cité University, Paris, France; Department of Neonatal Medicine, FHU Prem'Impact, Cochin-Port Royal Hospital, Assistance Publique-Hôpitaux de Paris, Paris Cité University, 75014 Paris, France. Electronic address: olivier.baud@aphp.fr. 850348 106293 10.1016/j.bbi.2026.106293 41548585 0889-1591 https://www.sciencedirect.com/science/article/pii/S0889159126000413 Objective: Pediatric traumatic brain injury (TBI) is a leading cause of death and disability in infants, whose neurodevelopmental consequences currently lack effective treatment. Since TBI is associated with neuroinflammation, modulation of the post-injury neuroinflammatory response is a promising strategy. Oxytocin is suggested to possess anti-inflammatory properties, and seems to play a role in clinical interventions that improve brain development in neonates. However, the underlying mechanisms remain unclear, as does its applicability to acute brain injury. Methods: Here, we assess the effects of chemogenetic activation of oxytocinergic neurons on acute neuroinflammation and on long-term brain development after TBI in postnatal day 7 (P7) male mice. Immunohistochemistry, RNA sequencing, ex-vivo MRI-diffusion tensor imaging, in-vivo functional ultrasound imaging and behavioral assays are used for assessment. Oxytocinergic neurons were chemogenetically activated daily between P7 and P10. Results: We show that chemogenetic activation of oxytocinergic neurons mitigates the acute neuroinflammatory response to TBI 24 h post-injury, where it reduces the expression of inflammation-related genes, and promotes brain repair and development gene pathways in microglia. In the long-term, early-life oxytocinergic neuron activation improves subcortical and cortical white matter damage after TBI, prevents hyperactivity and loss of social behavior, and restores TBI-induced alterations in resting-state functional connectivity of the isocortex. These effects were found 35 days after the last treatment session. Conclusions: Our findings enhance the understanding of neuroinflammation modulation by oxytocin, reveal its long-term effects, and support intervention associated with endogenous oxytocin release as a promising neuroprotective strategy in pediatric TBI. Microglia Neuroinflammation Neuroprotection Oxytocin Pediatric brain injury Dewey 616.89 Dewey 616.8 Dewey 618 Swiss National Science Foundation Regulating microglia reactivity to protect the developing brain: a role for oxytocinergic neurons 197462 CH Swiss National Science Foundation A translational assessment of central nervous system innate immunity to identify how social support and oxytocin interact to protect against Alzheimer’s disease 223414 CH 60 Département de psychiatrie 225 58 Département de pédiatrie, gynécologie et obstétrique 223 53 Département de neurosciences fondamentales 21A false 1221 Neuroimagerie moléculaire en psychiatrie 983 973 Les dysfonctions synaptiques du cerveau 971 1251 Prévention des complications néonatales d'origine périnatale 990 Brain, behavior, and immunity 133 fb282640-644f-42c5-aed0-a5a7ba246216 Article (Published version) Public 1-s2.0-S0889159126000413-main.pdf 22441022 application/pdf CC BY-4.0 649d55707421b5a0d95b6725745603f3b9befa2d847e6eb64a31db5420d9e5c5 30e2ee2b-4862-4309-8b3a-af93204f2b64 Supplemental data Public ScienceDirect_files_24Feb2026_09-13.zip 36714277 application/zip 03bb7657460e33ef6f89b97dd4e5efaf738bb09132c24c26822ca8b5b7042e32 openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Schirmbeck, Gabriel