The relationship between inflammasomes and the endoplasmic reticulum stress response in the injured spinal cord

Abstract

Study design: Animal study.

Objectives: The aim of this study is to investigate the influence of inflammasomes in the injured spinal cord of a rat spinal cord injury model.

Setting: University laboratory in Kanagawa, Japan.

Methods: A thoracic contusion spinal cord injury (SCI) was induced in female Sprague Dawley rats using an IH-impactor to create a moderate injury group (LI) and a severe injury group (HI). Using a sham group as a control, the injured spinal cords were removed at several time points after injury to evaluate the levels of inflammasome component proteins in the injured spinal cord by immunohistochemistry and Western Blot.

Results: Western blot analyses revealed that the expression of inflammasome component proteins leucine-rich repeat protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-2 significantly increased in the SCI animals compared to the sham animals. Thioredoxin interacting protein (TXNIP), which is a protein induced by ER stress that activates the NLRP3 inflammasome, was also significantly higher in the SCI animals. Immunohistochemistry revealed significantly higher expression of NLRP3, ASC, and Caspase-2 in oligodendrocyte progenitor cells (OPCs) of the SCI groups compared to astrocytes of the SCI groups and OPCs of the sham group.

Conclusions: Inflammasome component protein expression increases after SCI in association with increased ER stress. OPCs had significantly higher levels of inflammasome proteins compared to astrocytes, which may be associated with the high rates of OPC cell death after SCI.

Keywords: Endoplasmic; Inflammasome; NLRP3; Reticulum stress; Spinal cord injury; TXNIP.