24 - Progressive antenatal inflammation reduces high frequency EEG activity and cortical dendritic arborisation in late gestation fetal sheep

Monday, May 1, 2023

9:30 AM – 11:30 AM ET

Poster Number: 24
Publication Number: 24.434

Robert Galinsky, Hudson Institute of Medical Research, MELBOURNE, Victoria, Australia; Sharmony B. Kelly, The Hudson Institute/Monash University, Melbourne, Victoria, Australia; ingrid I. Dudink, Hudson Institute of Medical Research, BLACK ROCK, Victoria, Australia; Graeme Polglase, Hudson Institute of Medical Research, Melbourne, Victoria, Australia; Suzanne L. Miller, Monash University, Clayton, Victoria, Australia; Laura Bennet, The University of Auckland, Auckland, Auckland, New Zealand; Justin Dean, university of auckland, Auckland, Auckland, New Zealand; Alistair J.. Gunn, University of Auckland, Auckland, Auckland, New Zealand

Presenting Author(s)

Robert Galinsky, PhD (he/him/his)

Head, Perinatal inflammation and neurophysiology group
Hudson Institute of Medical Research
MELBOURNE, Victoria, Australia

Background: Antenatal infection/inflammation is associated with disturbances in neuronal connectivity, impaired cortical growth and poor neurodevelopmental outcomes. The pathophysiological substrates that underpin these inflammation-induced changes in neuronal connectivity and cortical development are poorly understood.

Objective: To determine whether inflammation in late gestation fetal sheep alters cortical neuronal microstructure. Furthermore, we examined whether inflammation-induced changes in cortical neuronal microstructure were associated with altered functional connectivity using electroencephalogram band power analysis.

Design/Methods: Fetal sheep (0.85 of gestation) were surgically instrumented for continuous electroencephalogram (EEG) recording and randomly assigned to repeated saline (control; n = 7) or lipopolysaccharide (LPS) infusions (0 h = 300 ng, 24 h = 600 ng, 48 h = 1200 ng; n = 7) to induce progressive inflammation. Sheep were euthanized 4 days after the first LPS infusion for assessment of cortical inflammation and injury using immunohistochemistry. Golgi staining was used to visualise the basal dendritic structure of cortical pyramidal neurons. Neuronal dendrites and spines were imaged and analysed using Imaris software. All analyses were undertaken on histological sections approximately 23 mm anterior to stereotaxic zero and between layers 3 to 5 of the somatosensory cortex.

Results:

LPS-exposure was associated with a reduction in the number of basal dendritic terminals, basal dendritic length, dendritic arborisation and number of dendritic spines (P< 0.05 vs. control). In LPS-exposed fetuses, numbers of (Iba-1+) microglia were increased compared to controls (P< 0.05), however there were no differences in numbers of (TUNEL+) apoptotic cells or numbers of (NeuN+) neurons between groups. In LPS-exposed fetuses, spectral band analysis showed an increase in delta (slow wave) frequency between 8 and 50 hours and a reduction in beta frequency between 18 and 96 hours (P< 0.05 vs. control).

Conclusion(s): After exposure to antenatal infection/inflammation, decreased dendritic arborisation, spine number and high frequency EEG activity may contribute to disturbed cortical neuronal growth and connectivity and subsequently impaired neurodevelopmental outcomes.