Mouse model of intrauterine inflammation: sex-specific differences in long-term neurologic and immune sequelae.
Preterm infants, especially those that are exposed to prenatal intrauterine infection or inflammation, are at a major risk for adverse neurological outcomes, including cognitive, motor and behavioral disabilities. We have previously shown in a mouse model that there is an acute fetal brain insult associated with intrauterine inflammation. The objectives of this study were: (1) to elucidate long-term (into adolescence and adulthood) neurological outcomes by assessing neurobehavioral development, MRI, immunohistochemistry and flow cytometry of cells of immune origin and (2) to determine whether there are any sex-specific differences in brain development associated with intrauterine inflammation. Our results have shown that prenatal exposure appeared to lead to changes in MRI and behavior patterns throughout the neonatal period and during adulthood. Furthermore, we observed chronic brain inflammation in the offspring, with persistence of microglial activation and increased numbers of macrophages in the brain, ultimately resulting in neuronal loss. Moreover, our study highlights the sex-specific differences in long-term sequelae. This study, while extending the growing literature of adverse neurologic outcomes following exposure to inflammation during early development, presents novel findings in the context of intrauterine inflammation.
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Tahani
T
Dada
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Jason M
JM
Rosenzweig
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Mofeedah
M
Al Shammary
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Wance
W
Firdaus
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Shorouq
S
Al Rebh
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Talaibek
T
Borbiev
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Aylin
A
Tekes
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Jiangyang
J
Zhang
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Eman
E
Alqahtani
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Susumu
S
Mori
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Mikhail V
MV
Pletnikov
Department of Neuroscience, Kennedy Krieger Institute, Baltimore, MD, United States.
Michael V
MV
Johnston
Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Department of Neuroscience, Kennedy Krieger Institute, Baltimore, MD, United States; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States. Electronic address: iburd@jhmi.edu.
Irina
I
Burd
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000196:embryology / Q000276:immunology; D007249:Inflammation / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000473:pathology; D012737:Sex Factors; D014599:Uterus / Q000503:physiopathology*
D008070:Lipopolysaccharides
Behavior; Brain damage; Intrauterine inflammation; Lipopolysaccharide; MRI; Mouse model; Preterm birth