title: Increased number of cerebellar granule cells and astrocytes in the internal granule layer in sheep following prenatal intra-amniotic injection of lipopolysaccharide.
abstract: Chorioamnionitis is an important problem in perinatology today, leading to brain injury and neurological handicaps. However, there are almost no data available regarding chorioamnionitis and a specific damage of the cerebellum. Therefore, this study aimed at determining if chorioamnionitis causes cerebellar morphological alterations. Chorioamnionitis was induced in sheep by the intra-amniotic injection of lipopolysaccharide (LPS) at a gestational age (GA) of 110 days. At a GA of 140 days, we assessed the mean total and layer-specific volume and the mean total granule cell (GCs) and Purkinje cell (PC) number in the cerebelli of LPS-exposed and control animals using high-precision design-based stereology. Astrogliosis was assessed in the gray and white matter (WM) using a glial fibrillary acidic protein staining combined with gray value image analysis. The present study showed an unchanged volume of the total cerebellum as well as the molecular layer, outer and inner granular cell layers (OGL and IGL, respectively), and WM. Interestingly, compared with controls, the LPS-exposed brains showed a statistically significant increase (+20.4%) in the mean total number of GCs, whereas the number of PCs did not show any difference between the two groups. In addition, LPS-exposed animals showed signs of astrogliosis specifically affecting the IGL. Intra-amniotic injection of LPS causes morphological changes in the cerebellum of fetal sheep still detectable at full-term birth. In this study, changes were restricted to the inner granule layer. These cerebellar changes might correspond to some of the motor or non-motor deficits seen in neonates from compromised pregnancies.
authors.affiliation: Department of Neuroscience and European Graduate School of Neuroscience, Maastricht University, Maastricht, The Netherlands.
authors.forename: Eveline
authors.initials: E
authors.lastname: Strackx
authors.forename: Markus
authors.initials: M
authors.lastname: Gantert
authors.forename: Veronique
authors.initials: V
authors.lastname: Moers
authors.forename: Imke A J
authors.initials: IA
authors.lastname: van Kooten
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rieke
authors.forename: Hanna
authors.initials: H
authors.lastname: Hürter
authors.forename: Marijke A M
authors.initials: MA
authors.lastname: Lemmens
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: L J I
authors.initials: LJ
authors.lastname: Zimmermann
authors.forename: Johannes S H
authors.initials: JS
authors.lastname: Vles
authors.forename: Yves
authors.initials: Y
authors.lastname: Garnier
authors.forename: Antonio W D
authors.initials: AW
authors.lastname: Gavilanes
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects; D002525:Cerebellar Cortex / Q000166:cytology* / Q000187:drug effects / Q000473:pathology*; D002526:Cerebellar Diseases / Q000139:chemically induced / Q000473:pathology*; D002821:Chorioamnionitis / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology*; D034561:Sheep, Domestic; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology