Statin Pre-Treatment Protects Brain Against Focal Cerebral Ischemia in Diabetic Mice

Çakmak, Atıl; Yemişçi, Müge; Köksoy, Cüneyt; Yazgan, Uğur; Dinçer, Deniz; Dalkara, Turgay

doi:10.1016/j.jss.2006.06.012

Cited by 24 publications

(23 citation statements)

References 31 publications

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“…This could potentially be mediated through antioxidant, antiapoptotic, antithrombotic, anti-inflammatory, or neuroprotective statin mechanisms or via enhanced cerebral repair. [5][6][7][8][9][10][12][13][14] There is further support from clinical studies in which statin-treated patients show cerebrovascular benefits, including enhanced collateral circulation, improved cerebrovascular reactivity to acetazolamide challenge, and in some but not all studies, improved infarct volumes. 29,30,[57][58][59] Statins may also have indirect benefits by reducing the frequency of recurrent stroke, coronary events, and infection.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In animal models, treatment with statins either before, or early after, cerebral arterial occlusion has been associated with reduced infarct volume and improved neurological function. [5][6][7][8][9][10]13,14 Data are conflicting regarding the relationship between acute statin therapy and outcome after human ischemic stroke. Some authors have reported improved survival and functional outcome associated with statin treatment, but these findings have not been consistently replicated.…”

Section: Ní Chróinín Et Al Statin Therapy and Outcome After Ischemic mentioning

confidence: 99%

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Statin Therapy and Outcome After Ischemic Stroke

Chróinín

Asplund

Åsberg

et al. 2013

Stroke

203

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Background and Purpose-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. Methods-The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients. Results-The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies restricted to of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). Conclusion-In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. 5-12 Experimental and clinical data also provide some evidence that statins may have neuroprotective effects after acute cerebral ischemia. [7][8][9][10][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In animal models, treatment with statins either before, or early after, cerebral arterial occlusion has been associated with reduced infarct volume and improved neurological function. [5][6][7][8][9][10]13,14 Data are conflicting regarding the relationship between acute statin therapy and outcome after human ischemic stroke. Some authors have reported improved survival and functional outcome associated with statin treatment, but these findings have not been consistently replicated. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][31][32][33][34][35][36] Interpretations can be difficult because of limited sample sizes in some reports and possible bias in statin allocation in other studies, particularly those in which statins were allocated in a nonrandomized fashion. Some authors have also reported worse outcomes in patients treated with the combination of acute statins and intravenous thro...

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Section: Discussionmentioning

confidence: 99%

Section: Ní Chróinín Et Al Statin Therapy and Outcome After Ischemic mentioning

confidence: 99%

Statin Therapy and Outcome After Ischemic Stroke

Chróinín

Asplund

Åsberg

et al. 2013

Stroke

203

View full text Add to dashboard Cite

show abstract

“…In mouse models of ischemic stroke, statin pretreatment has been shown to reduce infarct volume in both diabetic [20] and nondiabetic mice [17][18][19]26] . A recent study by Cakmak et al [20] compared statin pretreatment between diabetic and nondiabetic mice.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study by Cakmak et al [20] compared statin pretreatment between diabetic and nondiabetic mice. Among untreated mice, those with diabetes developed larger infarcts.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, statin withdrawal following stroke onset has been associated with an increased risk of death or dependency at 90 days [16] . Little is known about the mechanisms associated with this action in humans; however, animal models of ischemic stroke have shown that treatment with statins results in reduced brain infarct size [17][18][19][20] . The primary purpose of this study was to examine whether patients taking statins at the onset of ischemic stroke had smaller infarct volumes than those not taking statins.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Statin Pretreatment on Infarct Volume in Ischemic Stroke

Nicholas

Swearingen²,

Thomas³

et al. 2008

Neuroepidemiology

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Background: Treatment with statins reduces infarct volume in animal models of ischemic stroke, independently of the effect on cholesterol. This study examined this effect in humans by testing whether patients taking statins at onset of ischemic stroke had smaller infarct volumes than those not taking statins. Methods: The study design was a retrospective cohort analysis of all verified ischemic stroke patients admitted to the Medical University of South Carolina Hospital, in 2002–2006, with magnetic resonance diffusion-weighted imaging (DWI). Patients were grouped according to statin status at admission and compared relative to infarct volume, calculated (blinded to statin status) from DWI. Results: A smaller than median infarct volume following ischemic stroke was associated with the interaction of statin pretreatment and positive diabetes status. This association remained significant (p = 0.01) in multivariable analysis even after controlling for factors related to demographics, comorbidities and risk factors, clinical features on admission, use of other medications and stroke features. Conclusions: Among ischemic stroke patients in this study, infarct volume below the median was significantly associated with statin pretreatment among those with diabetes.

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Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review

Chatterjee

2007

Naunyn-Schmied Arch Pharmacol

191

157

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Renal ischemia-reperfusion (I-R) contributes to the development of ischemic acute renal failure (ARF). Multi-factorial processes are involved in the development and progression of renal I-R injury with the generation of reactive oxygen species, nitric oxide and peroxynitrite, and the decline of antioxidant protection playing major roles, leading to dysfunction, injury, and death of the cells of the kidney. Renal inflammation, involving cytokine/adhesion molecule cascades with recruitment, activation, and diapedesis of circulating leukocytes is also implicated. Clinically, renal I-R occurs in a variety of medical and surgical settings and is responsible for the development of acute tubular necrosis (a characteristic feature of ischemic ARF), e.g., in renal transplantation where I-R of the kidney directly influences graft and patient survival. The cellular mechanisms involved in the development of renal I-R injury have been targeted by several pharmacological interventions. However, although showing promise in experimental models of renal I-R injury and ischemic ARF, they have not proved successful in the clinical setting (e.g., atrial natriuretic peptide, low-dose dopamine). This review highlights recent pharmacological developments, which have shown particular promise against experimental renal I-R injury and ischemic ARF, including novel antioxidants and antioxidant enzyme mimetics, nitric oxide and nitric oxide synthase inhibitors, erythropoietin, peroxisome-proliferator-activated receptor agonists, inhibitors of poly(ADP-ribose) polymerase, carbon monoxide-releasing molecules, statins, and adenosine. Novel approaches such as recent research involving combination therapies and the potential of non-pharmacological strategies are also considered.

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Statin Pre-Treatment Protects Brain Against Focal Cerebral Ischemia in Diabetic Mice

Cited by 24 publications

References 31 publications

Statin Therapy and Outcome After Ischemic Stroke

Statin Therapy and Outcome After Ischemic Stroke

The Effect of Statin Pretreatment on Infarct Volume in Ischemic Stroke

Novel pharmacological approaches to the treatment of renal ischemia-reperfusion injury: a comprehensive review

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