PreprintArticleVersion 1This version is not peer-reviewed
A Novel Noninvasive Murine Model of Neonatal Hypoxic Ischemic Encephalopathy Demonstrates Developmental Delay and Motor Deficits with Activation of Inflammatory Pathways in Monocytes
Version 1
: Received: 30 July 2024 / Approved: 30 July 2024 / Online: 30 July 2024 (04:38:28 CEST)
How to cite:
Lemanski, E. A.; Collins, B. A.; Ebenezer, A. T.; Anilkumar, S.; Langdon, V.; Zheng, Q.; Ding, S.; Franke, K.; Schwarz, J. M.; Wright-Jin, E. A Novel Noninvasive Murine Model of Neonatal Hypoxic Ischemic Encephalopathy Demonstrates Developmental Delay and Motor Deficits with Activation of Inflammatory Pathways in Monocytes. Preprints2024, 2024072364. https://doi.org/10.20944/preprints202407.2364.v1
Lemanski, E. A.; Collins, B. A.; Ebenezer, A. T.; Anilkumar, S.; Langdon, V.; Zheng, Q.; Ding, S.; Franke, K.; Schwarz, J. M.; Wright-Jin, E. A Novel Noninvasive Murine Model of Neonatal Hypoxic Ischemic Encephalopathy Demonstrates Developmental Delay and Motor Deficits with Activation of Inflammatory Pathways in Monocytes. Preprints 2024, 2024072364. https://doi.org/10.20944/preprints202407.2364.v1
Lemanski, E. A.; Collins, B. A.; Ebenezer, A. T.; Anilkumar, S.; Langdon, V.; Zheng, Q.; Ding, S.; Franke, K.; Schwarz, J. M.; Wright-Jin, E. A Novel Noninvasive Murine Model of Neonatal Hypoxic Ischemic Encephalopathy Demonstrates Developmental Delay and Motor Deficits with Activation of Inflammatory Pathways in Monocytes. Preprints2024, 2024072364. https://doi.org/10.20944/preprints202407.2364.v1
APA Style
Lemanski, E. A., Collins, B. A., Ebenezer, A. T., Anilkumar, S., Langdon, V., Zheng, Q., Ding, S., Franke, K., Schwarz, J. M., & Wright-Jin, E. (2024). A Novel Noninvasive Murine Model of Neonatal Hypoxic Ischemic Encephalopathy Demonstrates Developmental Delay and Motor Deficits with Activation of Inflammatory Pathways in Monocytes. Preprints. https://doi.org/10.20944/preprints202407.2364.v1
Chicago/Turabian Style
Lemanski, E. A., Jaclyn M. Schwarz and Elizabeth Wright-Jin. 2024 "A Novel Noninvasive Murine Model of Neonatal Hypoxic Ischemic Encephalopathy Demonstrates Developmental Delay and Motor Deficits with Activation of Inflammatory Pathways in Monocytes" Preprints. https://doi.org/10.20944/preprints202407.2364.v1
Abstract
Neonatal hypoxic ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. There was significant upregulation of inflammatory genes in microglia 24 hours after hypoxia. Single cell RNAseq revealed two microglia subclusters of interest following HIE. Pseudobulk analysis revealed increased microglia motility gene expression and upregulation of epigenetic machinery and neurodevelopmental genes in macrophages following HIE. No sex differences were found in any measures. These results support a two-hit noninvasive model pairing MIA and hypoxia as a model for HIE in humans. This model results in a milder phenotype compared to established HIE models; however, HIE is a clinically heterogeneous injury resulting in a variety of outcomes in humans. The pathways identified in our model of HIE may reveal novel targets for therapy for neonates with HIE.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
