Cryogen spray cooling mitigates inflammation and injury-induced CISD2 decline in rat spinal cord hemisection model.

Cheng-Jen Chang,Muh-Shi Lin,Tzu-Yung Chen,Woon-Man Kung

doi:10.31083/j.jin.2020.04.255

Abstract

Therapeutic strategies for traumatic spinal cord injury generally involve rectifying concomitant destruction to the spinal cord from inflammation, mitochondrial dysfunction, and eventual neuronal apoptosis. Elevating the expression of spinal cord injury-attenuated CDGSH iron-sulfur domain-2 has been shown to mitigate the pathologies above. In the current work, hypothermia was induced via continuous cryogen spray cooling in a rat spinal cord hemisection model. Spinal cord injury was shown to elevate the mRNA expression of proinflammatory mediators, including NFκB, iNOS, TNF-α, and regulated upon activation, normal T-cell expressed and secreted as well as lower CDGSH iron-sulfur domain-2 expression. Cryogen spray cooling treatment was shown to attenuate inflammatory reactions and elevate CDGSH iron-sulfur domain-2 expression. Immunohistochemical analysis of the glial fibrillary acidic protein, caspase-3 and NeuN in spinal cord injured rats that underwent cryogen spray cooling treatment revealed notable reductions in injury-induced astrocytic activation, apoptosis, neuronal loss, and decline in CDGSH iron-sulfur domain-2 expression. These results demonstrate the CDGSH iron-sulfur domain-2 preserving effects of cryogen spray cooling, which could contribute to the prevention of astrocytic activation, astrocyte-mediated neuroinflammation, apoptosis, and neuron loss.

Highlights

The incidence of acute spinal cord injury (SCI) in the general population ranges from 15-40 cases per million worldwide
In the current spinal cord hemisection model, rats were subjected to cryogen spray cooling (CSC) treatment involving short spurts (20 milliseconds) at intervals of 5 spurts per min for 10 min, or untreated with CSC (Fig. 1A). quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to examine the mRNA expression of proinflammatory mediators at the site of SCI
The qRT-PCR analysis revealed that CDGSH iron sulfur domain 2 (CISD2) expression levels were significantly lower in the SCI only group than in the sham control group (P < 0.05, Fig. 2)

Summary

Introduction

The incidence of acute spinal cord injury (SCI) in the general population ranges from 15-40 cases per million worldwide. The pathophysiology of acute SCI initially involves significant insult to the spinal cord, resulting in immediate structural damage, including cell membrane rupture, myelin and axon damage, and microvascular destruction. Secondary injuries include profound proinflammatory responses, excitotoxicity, hyperoxidation, mitochondrial dysfunction, and eventual apoptotic cell death (Bethea and Dietrich, 2002; Houle and Tessler, 2003). Several molecular mechanisms have been implicated in SCI's pathogenesis, including hypoxia, ischemia, lipid peroxidation, free radical production, neutral protease activation, prostaglandin production, and programmed cell death (Bethea and Dietrich, 2002; Hung et al, 2007; Tator and Fehlings, 1991). CISD2 helps preserve the mitochondrial membrane's integrity and thereby prevents mitochon-

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