Effects of simvastatin and taurine on delayed cerebral vasospasm following subarachnoid hemorrhage in rabbits

Lin, Chih‐Ming; Zhao, Yuanli; Wan, Gang; Zhu, Anlin; Wang, Hao

doi:10.3892/etm.2016.3082

Cited by 9 publications

(7 citation statements)

References 43 publications

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“…However, in terms of the overall survival rate of patients, further development or combined therapies are required for achieving better outcomes for patients with intracerebral hemorrhage in an ICU setting. Of note, the present and previous studies indicated that Simvastatin is a prospective candidate drug for clinical therapy of patients with cerebrovascular disease ( 50 , 51 ).…”

Section: Discussionmentioning

confidence: 48%

Anti‑inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage in an intensive care unit

et al. 2017

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Intracerebral hemorrhage is one of the most common types of cerebrovascular disease in humans and often causes paralysis, a vegetative state and even death. Patients with acute intracerebral hemorrhage are frequently monitored in intensive care units (ICUs). Spontaneous intracerebral hemorrhage is associated with a higher rate of mortality and morbidity than other intracephalic diseases. The expression levels of inflammatory factors have important roles in inflammatory responses indicative of changes in a patient's condition and are therefore important in the monitoring and treatment of affected patients at the ICU as well as the development of therapeutic strategies for acute cerebral hemorrhage. The present study investigated the anti-inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage at an ICU, and inflammatory factors and cellular changes were systematically analyzed. The plasma concentrations of inflammatory factors, including interleukin (IL)-4, IL-6, IL-8 and IL-10, were evaluated by ELISAs. The plasma concentrations of inflammatory cellular changes were detected by using flow cytometry. The results demonstrated that after Simvastatin treatment of patients with acute cerebral hemorrhage at the ICU, the plasma concentrations of IL-4, IL-6, IL-8 and IL-10 were downregulated compared with those in placebo-treated controls. In addition, Simvastatin treatment at the ICU decreased lymphocytes, granulocytes and mononuclear cells in patients with acute cerebral hemorrhage. The levels of inflammatory factors were associated with brain edema in patients with acute cerebral hemorrhage treated at the ICU. In addition, the amount of bleeding was reduced in parallel with the inflammatory cell plasma concentration of lymphocytes, granulocytes and mononuclear cells. Importantly, Simvastatin treatment produced beneficial outcomes by improving brain edema and reducing the amount of bleeding. In conclusion, the present study demonstrated the efficacy of Simvastatin in treating acute intracerebral hemorrhage and evidenced the association between inflammatory responses and the progress of affected patients at the ICU, thereby providing insight for applying effective therapies for patients with acute intracerebral hemorrhage.

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Section: Discussionmentioning

confidence: 48%

Anti‑inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage in an intensive care unit

et al. 2017

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“…In this context, IL-6 has been shown to be an important mediator in apoptosis, and barrier disruptive effects and inhibition of IL-6 attenuated vascular inflammation and endothelial barrier disruption of retinal endothelial cells [22]. Aihara et al described higher mRNa expression of IL-6 in the endothelial wall of spastic basilar artery in dogs after SAH, a finding that was confirmed by other studies that showed a higher expression of IL-6 in endothelium of spastic cerebral arteries after SAH [23][24][25][26]. The role of IL-6 in endothelial damage and subsequently disruption of the blood-brain barrier has been described by Blecharz Lang et al [15], who noted a significant overexpression of IL-6 and the IL-6 receptor (IL-6R) in the endothelium after SAH.…”

Section: Il-6 In Relation To Dcvs and DCImentioning

confidence: 77%

Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy?

et al. 2021

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Delayed cerebral vasospasm (DCVS), early brain injury (EBI), and delayed cerebral ischemia (DCI) are devastating complications after aneurysmal subarachnoid hemorrhage (SAH). Interleukin (IL)-6 seems to be an important interleukin in the inflammatory response after SAH, and many studies describe a strong correlation between IL-6 and worse outcome. The aim of this study was to systematically review preclinical and clinical studies that evaluated systemic and cerebral IL-6 levels after SAH and their relation to DCVS, neuronal cell death, and DCI. We conducted two systematic literature searches using Pub-Med to identify preclinical and clinical studies evaluating the role of IL-6 after SAH. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 61 and 30 preclinical and clinical articles, respectively, were included in the systematic reviews. Of the preclinical studies in which IL-6 was measured in cerebrospinal fluid (CSF), parenchyma, and systemically, 100%, 94.4%, and 81.3%, respectively, showed increased expression of IL-6 after SAH. Preclinical results were mirrored by clinical findings in which elevated levels of IL-6 in CSF and plasma were found after SAH, correlating with DCVS, DCI, and worse outcome. Only two preclinical studies analyzed the direct inhibition of IL-6, which resulted in reduced DCVS and neuronal cell death. IL-6 is a marker of intracranial inflammation and plays a role in the pathophysiology of DCVS and DCI after SAH in preclinical animal models and clinical studies. Its inhibition might have therapeutic potential to improve the outcome of SAH patients.

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“…In addition to certain upregulated inflammatory factors in DCVS (5,7–9), a series of studies have been performed on the capacity of anti-inflammatory drugs to prevent DCVS. Simvastatin and taurine, for instance, have been demonstrated to alleviate DCVS following SAH in a rabbit model, which may be associated with the anti-inflammatory effect of statins (24). Although previous studies (7–9) have demonstrated that inflammatory response was involved in the cerebral vasospasm, they mainly focused on cytokines and adhesion molecules, including TNF-α and ICAM-1.…”

Section: Discussionmentioning

confidence: 99%

Potential role of poly (ADP‑ribose) polymerase in delayed cerebral vasospasm following subarachnoid hemorrhage in rats

Fan

Liu

et al. 2018

Exp Ther Med

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Poly (ADP-ribose) polymerase (PARP) serves a key role in several neurological disorders, however, the specific role of PARP in delayed cerebral vasospasm (DCVS) following subarachnoid hemorrhage (SAH) remains unclear. The present study was conducted to clarify the possible mechanism of PARP in DCVS with the treatment of 3-aminobenzamide (3-AB), a PARP inhibitor. In the preliminary experiment, an internal carotid artery puncture SAH model, a cisterna magna double injection SAH model and prechiasmatic cistern single injection SAH model were compared with respect to mortality and neurobehavioral test results. The prechiasmatic cistern single injection SAH model was chosen to induce DCVS in the formal experiment. In the formal experiment, a total of 96 Sprague Dawley rats were randomly allocated into the sham group, the SAH group and the SAH+3-AB group and then each group was further subdivided into days 3, 5, 7 and 14 post-SAH subgroups (n=8 for each subgroup). The prechiasmatic cistern single injection SAH model was established to induce DCVS. Neurobehavioral testing and HE staining were conducted to evaluate the degree of cerebral vasospasm. PARP activity was assessed by ELISA and immunohistochemistry. An electrophoretic mobility shift assay was used to detect nuclear factor (NF)-κB DNA-binding activity. The expression of monocyte chemotactic protein 1 (MCP-1) and C-reactive protein (CRP) were measured by western blotting. Cerebral vasospasm occurred following SAH and became most severe on around day 7 post-SAH. NF-κB activity, PARP activity, the expression of MCP-1 and CRP exhibited a similar time course to cerebral vasospasm. Treatment with 3-AB alleviated the degree of cerebral vasospasm. NF-κB activity, PARP activity and the expression of MCP-1 and CRP were also suppressed by 3-AB treatment. In conclusion, PARP may serve an important role in regulating the inflammatory response and ultimately contribute to DCVS. Therefore 3-AB may be a potential therapeutic agent for DCVS.

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Effects of simvastatin and taurine on delayed cerebral vasospasm following subarachnoid hemorrhage in rabbits

Cited by 9 publications

References 43 publications

Anti‑inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage in an intensive care unit

Anti‑inflammatory effects of Simvastatin in patients with acute intracerebral hemorrhage in an intensive care unit

Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy?

Potential role of poly (ADP‑ribose) polymerase in delayed cerebral vasospasm following subarachnoid hemorrhage in rats

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