Atorvastatin ameliorates early brain injury through inhibition of apoptosis and ER stress in a rat model of subarachnoid hemorrhage

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease with very poor prognosis. The aim of the present study was to evaluate the protective effects of atorvastatin on early brain injury (EBI) after SAH using a perforation SAH model. Male Sprague–Dawley rats were randomly divided into four groups: the sham group, the SAH group (model group), SAH + 10 mg.kg−1.day−1 atorvastatin (low atorvastatin group), and SAH + 20 mg.kg−1.day−1 atorvastatin (high atorvastatin group). Atorvastatin was administered orally by gastric gavage for 15 days before operation. At 24 h after SAH, we evaluated the effects of atorvastatin on brain water content, apoptosis by TUNEL assay and scanning electron microscope (SEM), and the expression of apoptosis-related proteins by immunofluorescence and Western blotting analysis. Compared with the sham group, we observed increased brain water content, significant apoptosis, and elevated levels of apoptosis-related proteins including caspase-3, CCAAT enhancer-binding protein homologous protein (CHOP), the 78-kDa glucose-regulated protein (GRP78), and aquaporin-4 (AQP4) in the SAH group. Atorvastatin administration under all doses could significantly reduce brain water content, apoptosis, and the expression levels of caspase-3, CHOP, GRP78, and AQP4 at 24 h after SAH. Our data show that early treatment with atorvastatin effectively ameliorates EBI after SAH through anti-apoptotic effects and the effects might be associated inhibition of caspase-3 and endoplasmic reticulum (ER) stress related proteins CHOP and GRP78.

Targeting IL‐10, ZO‐1 gene expression and IL‐6/STAT‐3 trans‐signaling by a combination of atorvastatin and mesalazine to enhance anti‐inflammatory effects and attenuates progression of oxazolone‐induced colitis

“…Our results showed that atorvastatin treatment significantly reduced caspase‐3 expression and this is in accordance with studies of Ref. [65–67]. Yang et al suggested that reduction in caspase‐3 expression by atorvastatin may be via increasing the phosphorylation of Akt1 during ischemia/reperfusion [66].…”

Controlled Decompression Attenuates Brain Injury in a Novel Rabbit Model of Acute Intracranial Hypertension

“…Caspase as a family of cysteine proteases that play an important part in apoptosis. Caspases-3 influences the process of neuronal apoptosis, and has a correlation with patient prognosis and mortality [14,15]. A total of 6 rabbits from each group were assessed.…”

The role and therapeutic potential of heat shock proteins in haemorrhagic stroke

“…Endoplasmic reticulum (ER) stress is believed to exert important roles in EBI . Glucose‐regulated protein 78 (GRP78), which belongs to HSP70 family, is mainly localized in the ER Acting as a chaperone that folds and transports proteins, GRP78 can bind to three ER sensors, protein kinase RNA‐like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol‐requiring protein 1α (IRE1) .…”

“…The alleviation of delayed vasospasm does not improve the clinical outcome in patients with SAH, which leads to a reasonable doubt as to whether delayed cerebral vasospasm affects the prognosis of SAH . Therefore, an increasing number of scholars have begun to support the theory that EBI is the chief cause of mortality and disability following SAH …”