Investigation of the Effects of Piceatannol on Endoplasmic Reticulum Stress on Brain in Rats with Experimental Subarachnoid Hemorrhage

Abstract

Aim: Subarachnoid hemorrhage (SAH) is a common neurologic disorder that accounts for brain injury, diminished neuron function, and neuronal death. Due to various options, SAH treatment remains lacking. Endoplasmic reticulum stress (ERS) in the brain is known as the disruption of the blood-brain barrier and triggered neuronal apoptosis, and contributes to SAH pathogenesis. This study aims to investigate the effects of piceatannol (PST) on ERS and neuronal apoptosis in an experimental SAH model in rats. Materials and Methods: For this purpose, 24 Wistar Albino male rats (8-10 w) were randomly divided into three groups (n=8); SHAM, SAH, and PST. SAH model was induced via injection of 120 μL of autologous blood into pre-chiasmatic cisterna. 30 mg/kg PST was injected intraperitoneally after 60 minutes from SAH inducement. Garcia’s neurologic examination, rotarod, and horizontal bar tests were applied for neurological evaluation. Frontal cortex specimens were harvested for histological and gene expression analysis. Results: Our results indicated that PST treatment significantly improved Garcia scores (p<0.01; p<0.05). In addition, PST decreased pyknosis (p<0.001) and edema (p<0.001) levels, and the number of damaged cells (p<0.01) and apoptotic cells (p<0.05). GRP78 (78-kDa glucose-regulated protein; p=0.01), ATF4 (Activating transcription factor 4; p=0.01), and CHOP (C/EBP homologous protein; p<0.05) gene expression levels of the SAH group were increased compared to SHAM. Moreover, PST significantly decreased the expression levels of p53 (p<0.01). Conclusion: Our results showed that PST indicated protective effects on ERS after SAH. It could be suggested that PST might be a supportive adjuvant agent in SAH management.

Keywords

• subarachnoid hemorrhage
• early brain injury
• piceatannol
• endoplasmic reticulum stress
• apoptosis