Protective effects of endoplasmic reticulum stress preconditioning on hippocampal neurons in rats with status epilepticus

Abstract

Objective To evaluate the protective effects of endoplasmic reticulum stress preconditioning induced by 2-deoxyglucose (2-DG) on hippocampal neurons of rats with status epilepticus (SE) and the possible mechanism.  Methods Ninety Sprague-Dawley (SD) rats were randomly enrolled into preconditioning group (N = 30), SE group (N = 30) and control group (N = 30). Each group was divided into 6 subsets (N = 5) according to six time points (before seizure, 6 h, 12 h, 1 d, 2 d and 7 d after seizure). The preconditioning group was administered 2-DG intraperitoneally with a dose of 150 mg/kg for 7 days, and the lithium-pilocarpine induced SE rat model was established on both preconditioning group and SE group. The rats were sacrificed at the above six time points, and the brains were removed to make paraffin sections. Nissl staining was performed by toluidine blue to evaluate the hippocampal neuronal damage after seizure, and the number of survival neurons in hippocampal CA1 and CA3 regions of the rats were counted. Immunohistochemical staining was performed to detect the expressions of glucose regulated protein 78 (GRP78) and X-box binding protein 1 (XBP-1) in hippocampal CA3 region of the rats.  Results The number of survival neurons in preconditioning group was much more than that in SE group at 7 d after seizure (t = 5.353, P = 0.000), and was more obvious in CA1 region. There was no significant hippocampal neuronal damage in control group. The expressions of GRP78 and XBP-1 in CA3 region of hippocampus in SE group at 6 h after seizure were significantly higher than that in control group (P = 0.000), and then kept increasing until reaching the peak at 2 d (P = 0.000, for all). The expressions of GRP78 and XBP-1 in hippocampal CA3 region in preconditioning group were significantly higher than that in control group before seizure (P = 0.000, for all). The level of GRP78 maintained the highest at 24 h and 2 d after seizure (P = 0.000, for all), while the XBP-1 level reached the peak at 24 h after seizure (P = 0.000). The expressions of GRP78 and XBP-1 in hippocampal CA3 region in preconditioning group were significantly higher than that in SE group at before seizure, 6, 12, 24 h after seizure (P = 0.000, for all), while there was no significant difference at 2, 7 d after seizure (P > 0.05).  Conclusions Endoplasmic reticulum stress preconditioning could protect hippocampal neurons from damage in rats with status epilepticus, in which the XBP-1-GRP78 signal pathway may be an important mechanism.

doi: 10.3969/j.issn.1672-6731.2014.12.008