RETRACTED ARTICLE: Preconditioning with pitavastatin, an HMG-CoA reductase inhibitor, attenuates C-Jun N-terminal kinase activation in experimental subarachnoid hemorrhage-induced apoptosis

Chang, Chih-Zen; Wu, Shao-Chun; Kwan, Aij‐Lie; Lin, Chih‐Lung

doi:10.1007/s00701-015-2399-3

Cited by 12 publications

(12 citation statements)

References 49 publications

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“…Several previous studies have demonstrated that statins may significantly inhibit the activity of matrix metalloproteinase (MMP)-2 and MMP-9 to maintain the stability of the blood/brain barrier (BBB) ( 17 , 21 ). Another study reported that pitavastatin exerted its neuroprotective effects by inhibiting the activation of c-Jun N-terminal kinase p46/p55 and reducing the expression levels of cleaved Caspase-9a and MMP-9 ( 22 ). Simvastatin has also been demonstrated to protect the cerebrum from neuronal excitotoxicity and cytotoxic edema by reducing the expression of phosphorylated Calcium/calmodulin-dependent protein kinase type II and AQP4 in experimental animals with ischemic stroke ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of atorvastatin on cerebral vessel autoregulation in an experimental rabbit model of subarachnoid hemorrhage

Chen¹,

Wu²,

Yang³

et al. 2017

Mol Med Report

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The aim of the present study was to assess the therapeutic effects of atorvastatin on cerebral vessel autoregulation and to explore the underlying mechanisms in a rabbit model of subarachnoid hemorrhage (SAH). A total of 48 healthy male New Zealand rabbits (weight, 2–2.5 kg) were randomly allocated into SAH, Sham or SAH + atorvastatin groups (n=16/group). The Sham group received 20 mg/kg/d saline solution, whereas 20 mg/kg/d atorvastatin was administered to rabbits in the SAH + atorvastatin group following SAH induction. Changes in diameter, perimeter and basilar artery (BA) area were assessed and expression levels of the vasoactive molecules endothelin-1 (ET-1), von Willebrand factor (vWF) and thrombomodulin (TM) were measured. Neuronal apoptosis was analyzed 72 h following SAH by terminal deoxynucleotidyl-transferase-mediated dUTP nick-end labeling (TUNEL) staining. The mortality rate in the SAH group was 18.75, 25% in the SAH + atorvastatin treated group and 0% in the Sham group (n=16/group). The neurological score in the SAH + atorvastatin group was 1.75±0.68, which was significantly higher compared with the Sham group (0.38±0.49; P<0.05). The BA area in the SAH + atorvastatin group (89.6±9.11) was significantly lower compared with the SAH group (115.4±11.0; P<0.01). The present study demonstrated that SAH induction resulted in a significant increase in the diameter, perimeter and cross-sectional area of the BA in the SAH + atorvastatin group. Administration of atorvastatin may significantly downregulate the expression levels of ET-1, vWF and TM (all P<0.01) vs. sham and SAH groups. TUNEL staining demonstrated that neuronal apoptosis was remarkably reduced in the hippocampus of SAH rabbits following treatment with atorvastatin (P<0.05). Atorvastatin treatment may alleviate cerebral vasospasm and mediate structural and functional remodeling of vascular endothelial cells, in addition to promoting anti-apoptotic signaling. These results provided supporting evidence for the use of atorvastatin as an effective and well-tolerated treatment for SAH in various clinical settings and may protect the autoregulation of cerebral vessels.

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Section: Discussionmentioning

confidence: 99%

Protective effects of atorvastatin on cerebral vessel autoregulation in an experimental rabbit model of subarachnoid hemorrhage

Chen¹,

Wu²,

Yang³

et al. 2017

Mol Med Report

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“…Therefore, the effects of acute statin post-treatment on SAH were questionable. However, a large number of experiments (7,9,14,15,25,26) have confirmed that statins prevent delay CVS, ameliorate EBI and improve the outcome of patients after SAH. However, the mechanism of EBI remained not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…We suggest that atorvastatin ameliorates early brain injury and improves patient prognosis after SAH. Chang et al (26) found that pitavastatin exerts its neuroprotective effect through the dual action of inhibiting cJNK (p46/ p55) activation and reducing cleaved caspase-9a and MMP-9 expression. Zhu et al (44) also demonstrated that simvastatin protected the cerebrum from neuronal excitotoxicity and cytotoxic edema by downregulating the expression of phosphorylated-CaMK II and AQP4 in an animal model of experimental ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of AQP4 expression in rabbits

Chen

Yang

Chen

et al. 2016

International Journal of Molecular Medicine

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The therapeutic effects of atorvastatin on early brain injury (EBI), cerebral edema and its association with aquaporin 4 (AQP4) were studied in rabbits after subarachnoid hemorrhage (SAH) using western blot analysis and the dry-wet method. Seventy-two healthy male New Zealand rabbits weighing between 2.5 and 3.2 kg were randomly divided into three groups: the SAH group (n=24), sham-operated group (n=24) and the SAH + atorvastatin group (n=24). A double SAH model was employed. The sham-operated group were injected with the same dose of saline solution, the SAH + atorvastatin group received atorvastatin 20 mg/kg/day after SAH. All rabbit brain samples were taken at 72 h after the SAH model was established successfully. Brain edema was detected using the dry-wet method after experimental SAH was induced; AQP4 and caspase-3 expression was measured by western blot analysis, and neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining at 72 h after SAH. The results indicated that brain edema and injury appeared soon after SAH, while brain edema and EBI were ameliorated and increased behavior scores were noted after prophylactic use of atorvastatin. Compared with the SAH group, the level of AQP4 and the cerebral content of water was significantly decreased (P<0.01) by atorvastatin, and TUNEL staining and studying the expression of caspase-3 showed that the apoptosis of neurons was reduced markedly both in the hippocampus and brain cortex by atorvastatin. The results suggest that atorvastatin ameliorated brain edema and EBI after SAH, which was related to its inhibition of AQP4 expression. Our findings provide evidence that atorvastatin is an effective and well-tolerated approach for treating SAH in various clinical settings.

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“…Currently, there are many kinds of treatments for CVS after SAH [13][14][15][16][17][18][19][20][21]. However, these methods can only reduce a part of occurrence of CVS [22].…”

Section: Discussionmentioning

confidence: 99%

Identification of OPN, TNC and E-selectin as potential recognition proteins in cerebral vasospasm after subarachnoid hemorrhage

et al. 2016

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Background: Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is a serious and significant health problem in the worldwide. There are still no effective therapies for treatment of CVS in patients suffering from SAH. Our early studies have demonstrated that the expression of connexin43 (Cx43, a member of gap junctional proteins) in cerebral spastic vessel is significantly up-regulated, and knocking down Cx43 with specific siRNA interference can significantly alleviate CVS after SAH. Therefore, Cx43 in cerebral vessel is a potential target in the treatment of CVS. However, Cx43 is widely distributed in many organs, particularly in the heart, and plays an important role in the physiological function. This study is aimed at identify whether OPN, TNC or E-selectin can be used as a target protein to be recognized in spastic cerebral vessels, then we can produce a carrier containing Cx43 siRNA or other inhibitors as a new potential treatment for CVS. Methods: Twenty eight male Sprague Dawley rats (weighing 300-350 g) were randomly divided into either SAH (n = 16) or sham group (n = 12). The double hemorrhage model was performed on day 0 and 1. All animals were sacrificed after performing India ink angiography on day 5. Initially, the expression of E-selectin, TNC and OPN in cerebral arteries, thoracic aorta and abdominal aorta were analyzed respectively by immunohistochemical staining, western blot in both groups. Then, only those with less expression in thoracic aorta, abdominal aorta and normal cerebral arteries, but higher expression in cerebral spastic arteries were further detected in the spinal cord, heart, kidney, liver, spleen, lung, pancreas, mesenteric and pulmonary arteries, retina and brain tissue, respectively.

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RETRACTED ARTICLE: Preconditioning with pitavastatin, an HMG-CoA reductase inhibitor, attenuates C-Jun N-terminal kinase activation in experimental subarachnoid hemorrhage-induced apoptosis

Cited by 12 publications

References 49 publications

Protective effects of atorvastatin on cerebral vessel autoregulation in an experimental rabbit model of subarachnoid hemorrhage

Protective effects of atorvastatin on cerebral vessel autoregulation in an experimental rabbit model of subarachnoid hemorrhage

Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of AQP4 expression in rabbits

Identification of OPN, TNC and E-selectin as potential recognition proteins in cerebral vasospasm after subarachnoid hemorrhage

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