Abstract
The treatment goal for spinal cord injury (SCI) is to repair neurites and suppress cellular apoptosis. This study is to investigate the effects of nuclear heme oxidase-1 (HO-1) on the acute spinal cord injury and the related mechanisms. The rat model of the SCI was established. On day 7, before model establishment, the adenovirus vector carrying nuclear HO-1 (Ad-GFP-HO-1CΔ23) was injected into the animals into the tenth thoracic spine (T10) segment by the intrathecal injection. Starting from after the model establishment to day 28, the recovery of motor function was assessed by the Basso-Beattie-Bresnahan (BBB) scoring method. Immunofluorescence was performed to detect the expression patterns of nuclear and cytoplasmic proteins. HE and Nissl staining methods were used to evaluate the structural damage and the number of surviving neurons near the injured area. The TUNEL method was conducted to evaluate the apoptotic degree. Protein expression levels were detected with the Western blot analysis. The BBB assay scores in the nuclear HO-1 group were significantly higher than the blank and adenovirus control groups. Moreover, compared to the blank and adenovirus control groups, the neuronal apoptosis in the nuclear HO-1 group was significantly alleviated. Furthermore, the expression levels of the endoplasmic reticulum stress-related proteins, i.e., CHOP, GRP78, and caspase-12, were significantly decreased in the nuclear HO-1 group. Nuclear HO-1 significantly improves the SCI, promotes the functional recovery, inhibits the endoplasmic reticulum stress, and alleviates the apoptotic process after SCI.
Highlights
Spinal cord injury (SCI) is a common traumatic disease with an extremely high disability rate
Recent reports have shown that the endoplasmic reticulum stress (ER stress) response is activated after the moderate contusion of the spinal cord in rodent models, and the inhibition of endoplasmic reticulum stress can improve the recovery of the hindlimb motor function [2, 3]
Our results showed that there were no significant difference in the BBB scores between the SCI group and the Ad-GFP group (Figure 3)
Summary
Spinal cord injury (SCI) is a common traumatic disease with an extremely high disability rate. The pathology of SCI could be divided into two stages, i.e., the primary damage caused by direct injury to the spinal cord tissue and the secondary damage including the axon destruction, neuronal death, inflammation, blood-brain barrier destruction, hypoxia, and ischemia [1]. These events during the secondary injuries would always lead to the neuronal death and dysfunction. The UPR could be activated by three signal pathways, involving the IRE1, ATF6, and PERK, respectively [5] During this process, the expression levels of apoptotic proteins are increased, further leading to neuronal apoptosis [6]. The association of nuclear HO-1 with the endoplasmic reticulum (ER) stressrelated proteins was studied, and the possible mechanism was analyzed
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