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. 2015 Mar 15;8(3):3309-17.
eCollection 2015.

Effects of hyperbaric oxygen on glucose-regulated protein 78 and c-Jun N-terminal kinase expression after spinal cord injury in rats

Xuehua Liu  1 , Chunsheng Li  2 , Fang Liang  1 , Yong Wang  3 , Zhuo Li  1 , Jing Yang  1
Affiliations

Effects of hyperbaric oxygen on glucose-regulated protein 78 and c-Jun N-terminal kinase expression after spinal cord injury in rats

Xuehua Liu et al. Int J Clin Exp Med. .

Abstract

Spinal cord injury (SCI) is not only devastating but also represents a public health burden for society. Endoplasmic reticulum stress (ERS) is implicated in secondary injury following damage to the SC. Hyperbaric oxygen (HBO) treatment can improve the recovery of motor function after SCI, but the effect of HBO on the ERS response is unknown. This study tested the hypothesis that HBO treatment protects against secondary SCI by inhibiting the ERS response via regulation of glucose-regulated protein (GRP) 78 and c-Jun N-terminal kinase (JNK) expression. Rats were randomly assigned to sham, SCI, and SCI + HBO groups and the extent of neuronal damage and neurological recovery were evaluated 1, 3, 7, and 14 days after surgery. GRP78 and JNK expression was evaluated by immunohistochemical, western blot, and real-time reverse transcription-polymerase chain reaction analyses, while caspase-3 activation was evaluated by enzyme-linked immunosorbent assay. SCI resulted in an upregulation in GRP78 and JNK expression compared to sham-operated animals. HBO treatment increased GRP78 level, but decreased that of JNK and suppressed caspase-3 activation as well as neuronal damage relative to the SCI group. In addition, hind limb motor function was improved by HBO treatment. HBO treatment reduces SCI-induced neuronal death and promotes the recovery of neurological function recovery by inhibiting the ERS response via modulation of GRP78 and JNK expression levels.

Keywords: Hyperbaric oxygen; c-Jun N-terminal kinase; glucose-regulated protein 78; spinal cord injury.

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Figures

Figure 1
Figure 1
BBB scores for hind limb motor function. Rats in the SCI groups were subjected to SC contusion using a 10-g weight dropped from a height of 25 mm. Sham-operated control animals underwent surgery without injury. The SCI + HBO group received HBO treatment (100% O2) after the surgery, while those in the Sham and SCI groups were exposed to normobaric air (21% O2) for the same amount of time. Motor function was evaluated 1, 3, 7, and 14 days post-surgery. Data represent mean ± SD. **P < 0.01 vs. SCI.
Figure 2
Figure 2
Histological analysis of the SC on day 3 after surgery. Experimental groups are as described in the Figure 1 legend. Tissue sections were stained with hematoxylin and eosin and visualized by light microscopy. The number of uninjured neurons was quantified at 200 × magnification. Data represent mean ± SD. *P < 0.05, **P < 0.01 vs. Sham; #P < 0.05 vs. SCI.
Figure 3
Figure 3
GRP78 and p-JNK expression in the SC 1 day after surgery. Experimental groups are as described in the Figure 1 legend. GRP78- and p-JNK-positive cells were identified by immunohistochemistry and analyzed at 400 × magnification.
Figure 4
Figure 4
GRP78 and p-JNK protein expression in the SC following SCI and HBO treatment. Experimental groups are as described in the Figure 1 legend. A: Representative immunoblots of GRP78 and p-JNK expression at indicated time points are shown. B: Quantitative analysis of GRP78 and p-JNK levels. Data represent mean ± SD. **P < 0.01 vs. Sham; #P < 0.05 vs. SCI.
Figure 5
Figure 5
GRP78 and p-JNK mRNA expression in the SC following SCI and HBO treatment. Experimental groups are as described in the Figure 1 legend. (A) GRP78 and (B) p-JNK mRNA expression was determined by real-time PCR at indicated time points. Data represent mean ± standard deviation. **P < 0.01 vs. Sham; #P < 0.05, ##P < 0.01 vs. SCI.
Figure 6
Figure 6
Activation of caspase-3 in the SC following SCI and HBO treatment. Experimental groups are as described in the Figure 1 legend. Activation of caspase-3 was determined by enzyme-linked immunosorbent assay at indicated time points. Data represent mean ± standard deviation. *P < 0.05, **P < 0.01 vs. Sham; #P < 0.05 vs. SCI.
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