Increasing Severity of Spinal Cord Injury Results in Microglia/Macrophages With Annular-Shaped Morphology and No Change in Expression of CD40 and Tumor Growth Factor-β During the Chronic Post-injury Stage

Elvira Ruslanovna Akhmetzyanova; Anna Viktorovna Timofeeva; Davran Khudaishukurovich Sabirov; Alexander Alexandrovich Kostennikov; Alexander Alexandrovich Rogozhin; Victoria James; S S Arkhipova; Albert Anatolevich Rizvanov; Yana Olegovna Mukhamedshina

doi:10.3389/fnmol.2021.802558

Increasing Severity of Spinal Cord Injury Results in Microglia/Macrophages With Annular-Shaped Morphology and No Change in Expression of CD40 and Tumor Growth Factor-β During the Chronic Post-injury Stage

Front Mol Neurosci. 2022 Feb 24:14:802558. doi: 10.3389/fnmol.2021.802558. eCollection 2021.

Affiliations

¹ Clinical Research Center for Precision and Regenerative Medicine, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
² Department of Neurology, Kazan State Medical Academy-Branch Campus of the Federal State Budgetary Educational Institution of Father Professional Education, Russian Medical Academy of Continuous Professional Education, Kazan, Russia.
³ Division of Biomedical Science, Faculty of Medicine and Health Sciences, School of Veterinary Medicine and Science, University of Nottingham Biodiscovery Institute, University Park, Nottingham, United Kingdom.
⁴ Department of Histology, Cytology and Embryology, Kazan State Medical University, Kazan, Russia.

Abstract

Determination of the quantitative composition of phenotypically and morphologically different populations of resident microglia and infiltrating macrophages in spinal cord injury (SCI) of various degrees of severity could lead to much needed novel therapeutic interventions in neurotrauma. In this regard, we investigated the CD40 and TGF-β expressing populations of microglia/macrophages and their morphological states in a rat model of SCI of varying severity. We are the first to describe the annular-shaped microglia/macrophages, the morphology of which was formed due to the spatial orientation of the processes that form round or oval micro-territories, which include disintegrating myelin fibers. This type of cell morphology was found only in the injured spinal cord and mainly in the white matter. At the same time, an assessment of the number of annular-shaped microglia/macrophages and the diameter of micro-territories formed by their processes showed an elevation in these indicators as the severity of SCI increased. While we did not find significant quantitative changes in the populations of Iba1⁺/CD40⁺ and Iba1⁺/TGF-β⁺ microglia/macrophages with increased severity of SCI in the chronic period (60 dpi), we did determine changes in the expression of cytokines and mRNAs of genes-encoding microglial marker proteins, finding the greatest changes on days 7 and 14 after SCI between experimental groups with varying severity.

Keywords: microglia; morphology; polarization; rat; spinal cord injury.