Early treatment with atorvastatin exerts parenchymal and vascular protective effects in experimental cerebral ischaemia

Potey, Camille; Ouk, Thavarak; Pétrault, Olivier; Pétrault, Maud; Bérézowski, Vincent; Salleron, Julia; Bordet, Régis; Gautier, Sophie

doi:10.1111/bph.13285

Cited by 31 publications

(24 citation statements)

References 40 publications

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“…13,14 Atorvastatin has been reported to promote angiogenesis in models of stroke and brain injury. 16,34,35 By reducing inflammation-induced vascular leakage and promoting angiogenesis, atorvastatin prevents the formation and accelerates the absorption of the hematoma to improve the neurological function of patients with CSDH.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Our study in a rat model of subdural hematoma supported this mechanism 12 and further demonstrated that blocking inflammation and immature angiogenesis promoted rapid hematoma absorption. 13,14 Second, statins (β-hydroxy β-methylglutaryl-CoA reductase inhibitors), which were originally developed for reducing low-density lipoprotein cholesterol levels in patients with hyperlipidemia, 15 have been shown to reduce inflammation in the vessel wall 16 and mobilize endothelial progenitor cells for vascular repairs. [17][18][19][20] Third, our pilot and uncontrolled study of 23 patients with CSDH found that oral atorvastatin (20 mg daily for 1-8 months) significantly reduced hematomas and improved clinical outcomes in 96% of participants, 21 which was consistent with a systematic literature review.…”

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confidence: 99%

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Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients

Jiang¹,

et al. 2018

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IMPORTANCE Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH.OBJECTIVE To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. DESIGN, SETTING, AND PARTICIPANTSThe Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified.INTERVENTIONS Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. MAIN OUTCOMES AND MEASURESThe primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week.RESULTS One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P = .003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P = .03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P = .03). No significant adverse events were reported.CONCLUSIONS AND RELEVANCE Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients

Jiang¹,

et al. 2018

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“…This may offset the diminished vasodilatation capacity of our patients and explain the decreased number of migraine attacks and their severity observed in our intervention group. It seems that atorvastatin prevents migraine attacks by improving the vasomotor performance in cerebral vessels (45,46).…”

Section: Discussionmentioning

confidence: 99%

Does Atorvastatin Help Prevent Classic Migraine Attacks? A Triple-Blind Controlled Clinical Trial

Ganji¹,

Majdinasab²,

Hesam³

et al. 2020

Preprint

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Background: Migraine is a painful and disabling nervous disorder which negatively affects the quality of life. Migraineurs may suffer from a generalized vasomotor dysfunction. Statins improve vasomotor and vascular function, with their pleiotropic effects. We aimed to assess efficacy and safety of adding Atorvastatin to prophylactic regimen in better control of classic migraine.Methods: This triple-blind controlled clinical trial was on 68 consecutive patients with history of classic migraine. An interval of at least one month was given to evaluate vitamin D3 level and eligibility. In patients with vitamin D3 deficiency, the correction was provided by administration of soft gelatin capsule of vitamin D supplementation. The patients were randomly assigned to receive atorvastatin 20mg plus sodium valproate 500mg or placebo plus sodium valproate 500mg once a day for two months. The patients were evaluated based for the number of attacks and pain severity based on Visual Analogue Scale. Results: There was a significant (p = 0.0001) improvement in severity of pain and number of migraine attacks by adding Atorvastin to the prophylactic regimen of patients. After controlling for variable parameters, the differences between two arms of the study was yet statistically significant (p = 0.0001). A significant number of participants in intervention group were satisfied by their treatment (p = 0.001). There was no remarkable difference in two arms of the study in terms of possible side effects (P =0.315).Conclusions: The results of present study suggested that adding atorvastatin to migraine preventive regimen may help reduce the number of acute attacks and pain severity. This modality did not cause considerable side effects and led to a better patient satisfaction.

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“…; Potey et al . ). Among the proposed mechanisms, those that directly boost the ability of neurons to survive an ongoing ischemic event are of special interest.…”

mentioning

confidence: 97%

“…; Potey et al . ), and hyperacute treatment with statins after stroke onset has been reported to improve the outcome of stroke patients (Montaner et al . ; Cappellari et al .…”

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confidence: 99%

Specific rescue by ortho‐hydroxy atorvastatin of cortical GABAergic neurons from previous oxygen/glucose deprivation: role of pCREB

Guirao

Martí-Sistac

DeGregorio-Rocasolano

et al. 2017

Journal of Neurochemistry

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The statin atorvastatin (ATV) given as a post-treatment has been reported beneficial in stroke, although the mechanisms involved are not well understood so far. Here, we investigated in vitro the effect of post-treatment with ATV and its main bioactive metabolite ortho-hydroxy ATV (o-ATV) on neuroprotection after oxygen and glucose deprivation (OGD), and the role of the pro-survival cAMP response element-binding protein (CREB). Post-OGD treatment of primary cultures of rat cortical neurons with o-ATV, but not ATV, provided neuroprotection to a specific subset of cortical neurons that were large and positive for glutamic acid decarboxylase (large-GAD neurons, GABAergic). Significantly, only these GABAergic neurons showed an increase in phosphorylated CREB (pCREB) early after neuronal cultures were treated post-OGD with o-ATV. We found that o-ATV, but not ATV, increased the neuronal uptake of glutamate from the medium; this provides a rationale for the specific effect of o-ATV on pCREB in large-GABAergic neurons, which have a higher ratio of synaptic (pCREB-promoting) vs extrasynaptic (pCREB-reducing) N-methyl-D-aspartate (NMDA) receptors (NMDAR) than that of small-non-GABAergic neurons. When we pharmacologically increased pCREB levels post-OGD in non-GABAergic neurons, through the selective activation of synaptic NMDAR, we observed as well long-lasting neuronal survival. We propose that the statin metabolite o-ATV given post-OGD boosts the intrinsic pro-survival factor pCREB in large-GABAergic cortical neurons in vitro, this contributing to protect them from OGD.

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Early treatment with atorvastatin exerts parenchymal and vascular protective effects in experimental cerebral ischaemia

Cited by 31 publications

References 40 publications

Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients

Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients

Does Atorvastatin Help Prevent Classic Migraine Attacks? A Triple-Blind Controlled Clinical Trial

Specific rescue by ortho‐hydroxy atorvastatin of cortical GABAergic neurons from previous oxygen/glucose deprivation: role of pCREB

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