The Effect Of Neuritin On Endoplasmic Reticulum Stress In Early Brain Injury After Subarachnoid Hemorrhage

Objective:This study aims to investigate the cortical neuron apoptosis, blood-brain barrier permeability and the expression levels of endoplasmic reticulum stress factor GRP78 and PERK in early brain injury after subarachnoid hemorrhage.To observe the effects of Neuritin on the cortical neuron apoptosis, blood-brain barrier permeability and the expression levels of endoplasmic reticulum stress factor GRP78 and PERK in early brain injury after subarachnoid hemorrhage. To provide the oretical basis for potential therapeutic targets in the future in early brain injury after subarachnoid hemorrhage. Methods:Sprague–Dawley rats(n=144) were divided into the Control group(n=36),Sham group(n=36),SAH group(n=36) and Neuritin group(n=36).Animals were killed on the 3rd,6th,12 th,24th,48 th and 72th(n=6) respectively.In the SAH group,blood was doubly injected into the prechiasmatic cistern of the rats.In the Neuritin group,the neuritin was injected into the lateral ventricles after 1h of every subgroup on the basics of SAH group.HE dye was used to identify the model.GRP78 proteins and PERK proteins were detected by Western blot.The BBB permeability was evaluated by detection of extravasated Evans Blue by using 144 adult male SD rats.The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTPnickend labeling(TUNEL) method. Results:The rats in SAH group showed a large amount of blood in subarachnoid space.HE staining observed a large number of red cell accumulation in subarachnoid space.The scores of the neurobehavior significantly decreased firstly and increased subsequently in SAH group and showed significant difference compared with the Control group(P<0.05).The scores of the neurobehavior significantly decreased firstly and increased subsequently in Neuritin group and showed significant difference compared with the SAH group(P <0.05).The scores of the neurobehavior in Neuritin group were improved than those in SAH group. The expression of the PERK protein increased firstly and decreased subsequently in SAH group,respectively and had statistical significance(P<0.05) compared with the the Control group.The expression of the PERK protein in Neuritin group respectively and had statistical significance(P<0.05) compared with the the SAH group.The expression of the GRP78 protein increased firstly and decreased subsequently in SAH group,respectively and had statistical significance(P<0.05) compared with the the Control group.The expression of the GRP78 protein increased firstly and decreased subsequently in Neuritin group, respectively and had statistical significance(P<0.05) compared with the the SAH group expect 3h.The changes of BBB permeability increased firstly and decreased subsequently in SAH group,respectively and had statistical significance(P<0.05) compared with the the Control group.The changes of BBB permeability increased firstly and decreased subsequently in Neuritin group, respectively and had statistical significance(P<0.05) compared with the the SAH group expect 24 h. Conclusion:There is ERS in EBI after SAH. Neuritin can significantly change the expression of endoplasmic reticulum stress factor-GRP78, PERK and influence the scores of the neurobehavior, the BBB permeability, the brain edema and the cortical neuron apoptosis after subarachnoid hemorrhage. Neuritin can obviously improve EBI after SAH.