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Assessing therapeutic response non-invasively in a neonatal rat model of acute inflammatory white matter injury using high-field MRI

Wyston C. Pierre, Luis Akakpo, Irène Londono, Philippe Pouliot, Sylvain Chemtob, Frédéric Lesage and Gregory A. Lodygensky

Article (2019)

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Abstract

Perinatal infection and inflammatory episodes in preterm infants are associated with diffuse white matter injury (WMI) and adverse neurological outcomes. Inflammation-induced WMI was previously shown to be linked with later hippocampal atrophy as well as learning and memory impairments in preterm infants. Early evaluation of injury load and therapeutic response with non-invasive tools such as multimodal magnetic resonance imaging (MRI) would greatly improve the search of new therapeutic approaches in preterm infants. Our aim was to evaluate the potential of multimodal MRI to detect the response of interleukin-1 receptor antagonist (IL-1Ra) treatment, known for its neuroprotective properties, during the acute phase of injury on a model of neonatal WMI. Rat pups at postnatal day 3 (P3) received intracerebral injection of lipopolysaccharide with systemic IL-1Ra therapy. 24h later (P4), rats were imaged with multimodal MRI to assess microstructure by diffusion tensor imaging (DTI) and neurochemical profile of the hippocampus with (1)H-magnetic resonance spectroscopy. Astrocyte and microglial activation, apoptosis and the mRNA expression of pro-inflammatory and necroptotic markers were assessed. During the acute phase of injury, neonatal LPS exposure altered the concentration of hippocampus metabolites related to neuronal integrity, neurotransmission and membrane integrity and induced diffusivity restriction. Just 24h after initiation of therapy, early indication of IL-1Ra neuroprotective effect could be detected in vivo by non-invasive spectroscopy and DTI, and confirmed with immunohistochemical evaluation and mRNA expression of inflammatory markers and cell death. In conclusion, multimodal MRI, particularly DTI, can detect not only injury but also the acute therapeutic effect of IL-1Ra suggesting that MRI could be a useful non-invasive tool to follow, at early time points, the therapeutic response in preterm infants.

Uncontrolled Keywords

*Diffusion tensor imaging; *High-field MRI; *IL-1Ra; *In vivo imaging; *Lipopolysaccharide; *Magnetic resonance spectroscopy; *Periventricular leukomalacia

Subjects: 2500 Electrical and electronic engineering > 2500 Electrical and electronic engineering
2500 Electrical and electronic engineering > 2502 Electromagnetics, compatibility and interference
9000 Health sciences > 9000 Health sciences
Department: Department of Electrical Engineering
Funders: Canadian Institutes of Health Research, Institute of Human Development, Child and Youth Health (IHDCYH), Research Center of CHU Sainte-Justine
Grant number: 136908
PolyPublie URL: https://publications.polymtl.ca/5087/
Journal Title: Brain, Behavior, and Immunity (vol. 81)
Publisher: Elsevier
DOI: 10.1016/j.bbi.2019.06.032
Official URL: https://doi.org/10.1016/j.bbi.2019.06.032
Date Deposited: 04 Aug 2022 14:56
Last Modified: 15 May 2023 22:03
Cite in APA 7: Pierre, W. C., Akakpo, L., Londono, I., Pouliot, P., Chemtob, S., Lesage, F., & Lodygensky, G. A. (2019). Assessing therapeutic response non-invasively in a neonatal rat model of acute inflammatory white matter injury using high-field MRI. Brain, Behavior, and Immunity, 81, 348-360. https://doi.org/10.1016/j.bbi.2019.06.032

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