TY - JOUR
T1 - Mouse model of intrauterine inflammation
T2 - Sex-specific differences in long-term neurologic and immune sequelae
AU - Dada, Tahani
AU - Rosenzweig, Jason M.
AU - Al Shammary, Mofeedah
AU - Firdaus, Wance
AU - Al Rebh, Shorouq
AU - Borbiev, Talaibek
AU - Tekes, Aylin
AU - Zhang, Jiangyang
AU - Alqahtani, Eman
AU - Mori, Susumu
AU - Pletnikov, Mikhail V.
AU - Johnston, Michael V.
AU - Burd, Irina
N1 - Funding Information:
This work was supported by Aramco Services Company Fellowship Fund (W.F., J.M.R.), NICHD K08HD073315 (I.B.), NINDS NS28208 (M.J.), NIH RO1 EB003543 (S.M.), and a grant support from Brain Science Institute, Johns Hopkins (SM).
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Behavior
KW - Brain damage
KW - Intrauterine inflammation
KW - Lipopolysaccharide
KW - MRI
KW - Mouse model
KW - Preterm birth
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U2 - 10.1016/j.bbi.2014.01.014
DO - 10.1016/j.bbi.2014.01.014
M3 - Article
C2 - 24486323
AN - SCOPUS:84898547563
SN - 0889-1591
VL - 38
SP - 142
EP - 150
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -