Region- and Time-Dependent Gene Expression Responses to Siponimod, Atorvastatin and Methylprednisolone After Spinal Cord Injury.

Authors

Katarina Kiss Bimbova, Alexandra Kisucka, Tomas Kuruc, Maria Ileninova, Karolina Kucharova, Lenka Ihnatova, Maria Bacova, Martina Magurova, Nadezda Lukacova

Published in

The European journal of neuroscience. Volume 64. Issue 9.

Abstract

Traumatic spinal cord injury (SCI) triggers a secondary injury cascade in which microglia, infiltrating macrophages and astrocytes influence tissue degeneration and repair. These responses are dynamic and region-dependent, yet the comparative effects of anti-inflammatory therapies remain unclear. We evaluated siponimod, atorvastatin and methylprednisolone after Th9 compression injury in rats. Gene expression was assessed by quantitative RT-PCR in rostral, lesion and caudal spinal cord segments at 2 and 6 weeks postinjury. At 2 weeks, all treatments reduced microglia/macrophage-associated and inflammatory transcripts, particularly rostrally, as shown by reduced Iba1 and iNOS expression. Siponimod and atorvastatin also decreased IL-1β rostrally, whereas siponimod was associated with region-specific increases in inflammatory markers at the lesion site and caudally. Siponimod most consistently increased microglia/macrophage-associated transcripts linked to immunoregulatory and reparative responses caudally, including IL1rn, TGF-β, SOCS3 and IL4Rα. It also reduced selected inflammatory astrocyte-associated markers and increased transcripts linked to repair-related processes, while atorvastatin and methylprednisolone showed mixed effects. At 6 weeks, none of the treatments consistently suppressed pro-inflammatory microglia/macrophage-associated markers. Siponimod was associated with elevated transcripts linked to immunoregulatory and repair-related processes, together with region-dependent increases in inflammatory markers. Astrocyte-associated reactivity markers were largely normalised, whereas remodelling-associated transcripts were altered. Treatments induced modest changes in neuronal/axonal and myelin-associated transcripts, predominantly rostrally, without significant functional improvement. Overall, these interventions differentially modulated microglia/macrophage- and astrocyte-associated gene expression, with siponimod producing the broadest, but mixed and region-dependent, gene-expression pattern. These findings highlight the regional and stage-dependent complexity of glial and inflammatory gene expression after pharmacological treatment of SCI.

PMID:
43014820
Bibliographic data and abstract were imported from PubMed on 12 Nov 2026.

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