An early neuroprotective effect of atorvastatin against subarachnoid hemorrhage

Chen, Junhui; Wu, Ting; Xia, Wen-Yuan; Zhong-hua, Shi; Zhang, Chunlei; Chen, Lei; Chen, Qianxue; Wang, Yuhai

doi:10.4103/1673-5374.280326

Cited by 35 publications

(35 citation statements)

References 41 publications

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“…The severity of brain edema was evaluated by measuring the brain water content using the standard wet-dry method, as previously reported ( 15 , 33 , 34 ). The mice were sacrificed 72 h following ICH, and the entire brain was harvested and separated into the ipsilateral and contralateral cortex, ipsilateral and contralateral basal ganglia, and cerebellum (wet weight).…”

Section: Methodsmentioning

confidence: 99%

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Perampanel, an AMPAR antagonist, alleviates experimental intracerebral hemorrhage‑induced brain injury via necroptosis and neuroinflammation

et al. 2021

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Spontaneous intracerebral hemorrhage (ICH) is a subtype of stroke with high mortality and morbidity due to the lack of effective therapies. The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist perampanel has been reported to alleviate early brain injury following subarachnoid hemorrhage and traumatic brain injury by reducing reactive oxygen species, apoptosis, autophagy, and necroptosis. Necroptosis is a caspase-independent programmed cell death mechanism that serves a vital role in neuronal cell death following ICH. However, the precise role of necroptosis in perampanel-mediated neuroprotection following ICH has not been confirmed. The present study aimed to investigate the neuroprotective effects and potential molecular mechanisms of perampanel in ICH-induced early brain injury by regulating neural necroptosis in C57BL/6 mice and in a hemin-induced neuron damage cell culture model. Mortality, neurological score, brain water content, and neuronal death were evaluated. The results demonstrated that perampanel treatment increased the survival rate and neurological score, and increased neuron survival. In addition, perampanel treatment downregulated the protein expression levels of receptor interacting serine/threonine kinase (RIP) 1, RIP3, and mixed lineage kinase domain like pseudokinase, and of the cytokines IL-1β, IL-6, TNF-α, and NF-κB. These results indicated that perampanel-mediated inhibition of necroptosis and neuroinflammation ameliorated neuronal death in vitro and in vivo following ICH. The neuroprotective capacity of perampanel was partly dependent on the PTEN pathway. Taken together, the results of the present study demonstrated that perampanel improved neurological outcomes in mice and reduced neuronal death by protecting against neural necroptosis and neuroinflammation.

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Section: Methodsmentioning

confidence: 99%

“…Western blot analysis was performed as indicated previously ( 34 ). Briefly, cerebral cortex samples or HT22 cell homogenates were collected using RIPA lysis buffer (Beyotime Institute of Biotechnology) containing protease inhibitor cocktail (Sigma-Aldrich; Merck KGaA), dissolved, and separated by 10% SDS-PAGE.…”

Section: Methodsmentioning

confidence: 99%

Perampanel, an AMPAR antagonist, alleviates experimental intracerebral hemorrhage‑induced brain injury via necroptosis and neuroinflammation

et al. 2021

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“…Statins can reduce the concentration of glutamate by upregulation of nitric oxide synthase, and Jiang [28] also found that statins can inhibit 5-HT and 5-HTT expression in chronic obstructive pulmonary disease and pulmonary artery hypertension, then it may be ameliorated delirium by regulating neurotransmitters. Many previous studies indicated that statins can alleviate cerebral vasospasm, cerebral perfusion, prevents endothelial dysfunction, and ameliorating neuronal apoptosis and brain injury [7,9,10].…”

Section: Discussionmentioning

confidence: 99%

“…Statins, as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are widely used in cardiovascular disorders as cholesterol-lowering medications. Recent studies had indicated that statins have been proven to exert pleiotropic effects, including anti-inflammatory, antioxidative stress, inhibit platelet aggregation, and neuroprotection [7][8][9][10]. As the neuroprotection related molecular mechanism was similar to the delirium, so it indicated that statins may prevent delirium.…”

Section: Introductionmentioning

confidence: 99%

Effects of Perioperative Rosuvastatin for Postoperative Delirium After Elderly General Anesthesia Patients: A Randomized, Double-Blind, and Placebo-Controlled Trial

Luo

et al. 2021

Preprint

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Background: Experimental evidence has indicated the benefits of statins for the treatment of postoperative delirium. Previously clinical trials had no definite conclusions of statins on delirium. Some clinical trials indicated statins can reduce postoperative delirium and improve outcome, while some studies showed negative results. Therefore, the present study tries to evaluate whether perioperative rosuvastatin treatment could reduce the incidence of delirium and improve clinical outcomes. Methods: This was a randomized, double-blind, and placebo-controlled trial in a single-center in Jiangsu, China. This study enrolled patients aged more than 60 years old who present selective general anesthesia operation, with informed consent. A computer-generated randomization sequence (in a 1:1 ratio) was used to randomly assign patients to receive either rosuvastatin (40 mg/day) or placebos. Participants, care providers, and investigators were all masked to group assignment. The primary endpoint was the incidence of delirium, assessed twice daily with the Confusion Assessment Method during the first 7 postoperative days. Analyses were performed by intention-to-treat and safety populations. Results: Between Jan 1, 2017, and Jan 1, 2020, 3512 patients were assessed. A total of 821 were randomly assigned to receive either a placebo (n=411) or rosuvastatin (n=410). The incidence of postoperative delirium was significantly lower in the rosuvastatin group (23 [5.6%] of 410 patients) than the placebo group (42 [13.5%] of 411 patients (OR=0.522, 95% CI 0.308-0.885; p<0.05). No significant difference on 30-day all-cause mortality (6.1% vs 8.7 %, OR 0.67, P=0.147, 95% CI 0.39–1.2) between two groups. Rosuvastatin can decrease the hospitalization time (13.8±2.5 vs 14.2±2.8, P=0.03) and hospitalization expenses (9.3±2.5 vs 9.8±2.9, P=0.007). No statistical significance between the two groups on abnormal liver enzymes (9.0% vs 7.1%, P=0.30, OR=1.307, 95% CI 0.787-2.169) and rhabdomyolysis (0.73% vs 0.24%, P=0.37, OR=3.020, 95% CI 0.31-29.2. Conclusion: The current study suggests that perioperative rosuvastatin treatment can reduce the incidence of delirium after elective general anesthesia operation. However, no evidence was found that rosuvastatin can improve clinical outcomes. The therapy was safe. Further investigation is necessary to fully understand the potential usefulness of dexmedetomidine in older patients. Trial registration: chictr.org.cn, ChiCTR-IPR-17011984(Registered date: 13/07/2017). The manuscript adheres to CONSORT guidelines.

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“…The standard wet-dry method was used to compute the brain water content, as previously reported 19 , 20 . The entire brain tissue was taken for water content detection immediately after the animals were killed.…”

Section: Methodsmentioning

confidence: 99%

Controlled decompression alleviates early brain injury in rabbit intracranial hypertension model by regulating apoptosis/necroptosis

et al. 2021

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Purpose To evaluate the effects of controlled decompression and rapid decompression, explore the potential mechanism, provide the theoretical basis for the clinical application, and explore the new cell death method in intracranial hypertension. Methods Acute intracranial hypertension was triggered in rabbits by epidural balloon compression. New Zealand white rabbits were randomly put into the sham group, the controlled decompression group, and the rapid decompression group. Brain water content, etc., was used to evaluate early brain injury. Western blotting and double immunofluorescence staining were used to detect necroptosis and apoptosis. Results Brain edema, neurological dysfunction, and brain injury appeared after traumatic brain injury (TBI). Compared with rapid decompression, brain water content was significantly decreased, neurological scores were improved by controlled decompression treatment. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining showed neuron death decreased in the controlled decompression group. Compared with rapid decompression, it was also found that apoptosis-related protein caspase-3/ tumor necrosis factor (TNF)-a was reduced markedly in the brain cortex and serum, and the expression levels of necroptosis-related protein, receptor-interacting protein 1 (RIP1)/receptor-interacting protein 1 (RIP3) reduced significantly in the controlled decompression group. Conclusions Controlled decompression can effectively reduce neuronal damage and cerebral edema after craniocerebral injury and, thus, protect the brain tissue by alleviating necroptosis and apoptosis.

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An early neuroprotective effect of atorvastatin against subarachnoid hemorrhage

Cited by 35 publications

References 41 publications

Perampanel, an AMPAR antagonist, alleviates experimental intracerebral hemorrhage‑induced brain injury via necroptosis and neuroinflammation

Perampanel, an AMPAR antagonist, alleviates experimental intracerebral hemorrhage‑induced brain injury via necroptosis and neuroinflammation

Effects of Perioperative Rosuvastatin for Postoperative Delirium After Elderly General Anesthesia Patients: A Randomized, Double-Blind, and Placebo-Controlled Trial

Controlled decompression alleviates early brain injury in rabbit intracranial hypertension model by regulating apoptosis/necroptosis

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