Infantile status epilepticus disrupts myelin development

Petra Bencurova, Hanne Laakso, Raimo A. Salo, Ekaterina Paasonen, Eppu Manninen, Jaakko Paasonen, Shalom Michaeli, Silvia Mangia, Martin Bares, Milan Brazdil, Hana Kubova, Olli Gröhn

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Temporal lobe epilepsy (TLE) is the most prevalent type of epilepsy in adults; it often starts in infancy or early childhood. Although TLE is primarily considered to be a grey matter pathology, a growing body of evidence links this disease with white matter abnormalities. In this study, we explore the impact of TLE onset and progression in the immature brain on white matter integrity and development utilising the rat model of Li-pilocarpine-induced TLE at the 12th postnatal day (P). Diffusion tensor imaging (DTI) and Black-Gold II histology uncovered disruptions in major white matter tracks (corpus callosum, internal and external capsules, and deep cerebral white matter) spreading through the whole brain at P28. These abnormalities were mostly not present any longer at three months after TLE induction, with only limited abnormalities detectable in the external capsule and deep cerebral white matter. Relaxation Along a Fictitious Field in the rotating frame of rank 4 indicated that white matter changes observed at both timepoints, P28 and P72, are consistent with decreased myelin content. The animals affected by TLE-induced white matter abnormalities exhibited increased functional connectivity between the thalamus and medial prefrontal and somatosensory cortex in adulthood. Furthermore, histological analyses of additional animal groups at P15 and P18 showed only mild changes in white matter integrity, suggesting a gradual age-dependent impact of TLE progression. Taken together, TLE progression in the immature brain distorts white matter development with a peak around postnatal day 28, followed by substantial recovery in adulthood. This developmental delay might give rise to cognitive and behavioural comorbidities typical for early-onset TLE.

Original languageEnglish (US)
Article number105566
JournalNeurobiology of Disease
Volume162
DOIs
StatePublished - Jan 2022

Bibliographical note

Funding Information:
This work was supported by the EUH2020 Marie Skłodowska RISE project MICROBRADAM [grant number # 691110 ], Academy of Finland [grant number 298007], Czech Science Foundation [grant number 19-11931S ], European Regional Development Fund project PHARMABRAIN [grant number CZ.02.1.01/0.0/0.0/16_025/000744 (co-supported by EU )], and the support for long-term conceptual development of research organization RVO [grant number 67985823 ]. SMi and SMa were partially supported by the National Institutes of Health [award number P41 EB027061 ]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
The authors are grateful to Maarit Pulkkinen for her assistance with animal care and dissections in the MRI rat cohort and to Blanka Cejkova for histology. Experiments were conducted using MRI equipment in the Biomedical Imaging Unit at the University of Eastern Finland, which is part of EuroBioImaging ESFRI. This work was supported by the EUH2020 Marie Skłodowska RISE project MICROBRADAM [grant number #691110], Academy of Finland [grant number 298007], Czech Science Foundation [grant number 19-11931S], European Regional Development Fund project PHARMABRAIN [grant number CZ.02.1.01/0.0/0.0/16_025/000744 (co-supported by EU)], and the support for long-term conceptual development of research organization RVO [grant number 67985823]. SMi and SMa were partially supported by the National Institutes of Health [award number P41 EB027061]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2021 The Authors

Keywords

  • Animal model
  • Histology
  • MRI
  • Myelin development
  • Status Epilepticus
  • Temporal Lobe Epilepsy
  • Thalamocortical connectivity
  • White matter integrity

Center for Magnetic Resonance Research (CMRR) tags

  • NMC
  • P41

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Fingerprint

Dive into the research topics of 'Infantile status epilepticus disrupts myelin development'. Together they form a unique fingerprint.

Cite this