TY - JOUR
T1 - Increased Number of Cerebellar Granule Cells and Astrocytes in the Internal Granule Layer in Sheep Following Prenatal Intra-amniotic Injection of Lipopolysaccharide
AU - Strackx, Eveline
AU - Gantert, Markus
AU - Moers, Veronique
AU - van Kooten, Imke A. J.
AU - Rieke, Rebecca
AU - Hurter, Hanna
AU - Lemmens, Marijke A. M.
AU - Steinbusch, Harry W. M.
AU - Zimmermann, L. J. I.
AU - Vles, Johannes S. H.
AU - Garnier, Yves
AU - Gavilanes, Antonio W. D.
AU - Kramer, Boris W.
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Chorioamnionitis
KW - LPS
KW - Intra-amniotic
KW - Fetal
KW - Cerebellum
KW - Granule cell loss
KW - Astrocytes
KW - Stereology
U2 - 10.1007/s12311-011-0297-7
DO - 10.1007/s12311-011-0297-7
M3 - Article
C2 - 21773814
SN - 1473-4222
VL - 11
SP - 132
EP - 144
JO - Cerebellum
JF - Cerebellum
IS - 1
ER -