Effect of hypoxic preconditioning on endoplasmic reticulum stress after traumatic brain injury in rats

Abstract

Objective To explore the effect of hypoxic preconditioning (HPC) on endoplasmic reticulum stress after traumatic brain injury in rats. Methods Forty-eight Sprague Dawley rats were randomly divided into HPC group (HPC modeling) and non-HPC group (without HPC modeling), with 24 rats in each group. And then, each of the group was further divided into four sub-groups (n=6): three sub-groups after traumatic brain injury (TBI) for one, 3 and 7 days (TBI modeling, and drawing and observation after various TBI treatment times), and a control sub-group (without any treatment). HPC models were induced in the low-pressure oxygen chamber for 3 h daily continuing for 3 d. TBI models were established by modified Freeny's freely falling equipment. Modified neurological severity scale (mNSS) scores of the rats were recorded after brain injury. C/EBP homologous protein (CHOP) mRNA and protein expressions were detected by quantitative real-time PCR (qRT-PCR) and Western blotting. TUNEL was used to evaluate the apoptotic rate and the correlation between CHOP levels and apoptotic rate was analyzed. Results The mNSS scores, relative CHOP mRNA and protein expressions, and apoptotic rate in the one, 3 and 7 days subgroups after TBI were significantly higher than those in the control group (P<0.05); and these levels peaked at 3 d; the mNSS scores, relative CHOP mRNA and protein expressions, and apoptotic rate in HPC group were significantly lower than those in the non-HCP group (P<0.05); and the correlation analysis showed the CHOP expressions were positively correlated with apoptotic rate in the in HPC group and non-HCP group (r=0.957, P=0.000; r=0.966, P=0.000). Conclusion HPC can down-regulate the expression of pro-apoptotic protein CHOP which participates in endoplasmic reticulum stress pathway, reduce neuronal apoptosis and improve neurological function. Key words: Hypoxic preconditioning; Craniocerebral trauma; C/EBP homologous protein; Endoplasmic reticulum stress; Apoptosis