10.3389/fncel.2018.00055.s003 Robin Cloarec Robin Cloarec Sylvian Bauer Sylvian Bauer Natacha Teissier Natacha Teissier Fabienne Schaller Fabienne Schaller Hervé Luche Hervé Luche Sandra Courtens Sandra Courtens Manal Salmi Manal Salmi Vanessa Pauly Vanessa Pauly Emilie Bois Emilie Bois Emilie Pallesi-Pocachard Emilie Pallesi-Pocachard Emmanuelle Buhler Emmanuelle Buhler François J. Michel François J. Michel Pierre Gressens Pierre Gressens Marie Malissen Marie Malissen Thomas Stamminger Thomas Stamminger Daniel N. Streblow Daniel N. Streblow Nadine Bruneau Nadine Bruneau Pierre Szepetowski Pierre Szepetowski Table2.XLSX Frontiers 2018 cytomegalovirus microglia rat model fetal brain neurological outcome 2018-03-06 04:28:26 Dataset https://frontiersin.figshare.com/articles/dataset/Table2_XLSX/5950813 <p>Congenital cytomegalovirus (CMV) infections represent one leading cause of neurodevelopmental disorders. Recently, we reported on a rat model of CMV infection of the developing brain in utero, characterized by early and prominent infection and alteration of microglia—the brain-resident mononuclear phagocytes. Besides their canonical function against pathogens, microglia are also pivotal to brain development. Here we show that CMV infection of the rat fetal brain recapitulated key postnatal phenotypes of human congenital CMV including increased mortality, sensorimotor impairment reminiscent of cerebral palsy, hearing defects, and epileptic seizures. The possible influence of early microglia alteration on those phenotypes was then questioned by pharmacological targeting of microglia during pregnancy. One single administration of clodronate liposomes in the embryonic brains at the time of CMV injection to deplete microglia, and maternal feeding with doxycyxline throughout pregnancy to modify microglia in the litters' brains, were both associated with dramatic improvements of survival, body weight gain, sensorimotor development and with decreased risk of epileptic seizures. Improvement of microglia activation status did not persist postnatally after doxycycline discontinuation; also, active brain infection remained unchanged by doxycycline. Altogether our data indicate that early microglia alteration, rather than brain CMV load per se, is instrumental in influencing survival and the neurological outcomes of CMV-infected rats, and suggest that microglia might participate in the neurological outcome of congenital CMV in humans. Furthermore this study represents a first proof-of-principle for the design of microglia-targeted preventive strategies in the context of congenital CMV infection of the brain.</p>