Treatment With Statins After Induction of Focal Ischemia in Rats Reduces the Extent of Brain Damage

Sironi, Luigi; Cimino, Mauro; Guerrini, Uliano; Calvio, Anna Maria; Lodetti, Barbara; Asdente, M.; Balduini, Walter; Paoletti, Rodolfo; Tremoli, Elena

doi:10.1161/01.atv.0000044458.23905.3b

Cited by 178 publications

(130 citation statements)

References 40 publications

(34 reference statements)

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“…Posttreatment: In addition to these protective effects induced by the long-term pretreatment with statins, the therapeutic benefit of statins was found to extend to a 3-h poststroke treatment paradigm (Sironi et al, 2003). In this study, rats were exposed to permament occlusion of the MCA and brain infarct volume was measured by apparent diffusion coefficient maps and T2-weighted images by MRI at 24 and 48 h (Sironi et al, 2003).…”

Section: Experimental Evidencementioning

confidence: 90%

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Statins and Stroke

Endres

2005

J Cereb Blood Flow Metab

160

110

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Inhibitors of HMG-CoA reductase (statins) are potent cholesterol-lowering drugs. Large clinical trials have shown that statins reduce the incidence of cerebrovascular events, which might be surprising because cholesterol is not an established risk factor for stroke. In addition to their cholesterollowering properties, statins exert a number of pleiotropic, vasculoprotective actions that include improvement of endothelial function, increased nitric oxide (NO) bioavailability, antioxidant properties, inhibition of inflammatory responses, immunomodulatory actions, regulation of progenitor cells, and stabilization of atherosclerotic plaques. In fact, statins augment cerebral blood flow and confer significant protection in animal models of stroke partly via mechanisms related to the upregulation of endothelial nitric oxide synthase. Retrospective clinical evidence suggests that long-term statin administration may not only reduce stroke risk but also improve outcome. Early secondary prevention trials are underway to test the hypothesis that statin treatment initiated immediately after an event improves short-term outcome. Lastly, recent evidence suggests that sudden discontinuation of statin treatment leads to a rebound effect with downregulation of NO production. Withdrawal of statin treatment may impair vascular function and increase morbidity and mortality in patients with vascular disease.

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Section: Experimental Evidencementioning

confidence: 90%

“…In this study, rats were exposed to permament occlusion of the MCA and brain infarct volume was measured by apparent diffusion coefficient maps and T2-weighted images by MRI at 24 and 48 h (Sironi et al, 2003).…”

Section: Experimental Evidencementioning

confidence: 99%

Statins and Stroke

Endres

2005

J Cereb Blood Flow Metab

160

110

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“…The promising neuroprotective benefit of the statins in acute ischemic stroke [125][126][127] has led to a similar evaluation in ICH models. In the autologous whole blood model, atorvastatin at 2 mg/kg was beneficial, and higher doses did not improve outcome or reduce the extent of injury [128].…”

Section: Anti-inflammatory Agents: Statinsmentioning

confidence: 99%

Treatment Targets in Intracerebral Hemorrhage

Sangha

Gonzales

2011

Neurotherapeutics

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Intracerebral hemorrhage (ICH) imparts a higher mortality and morbidity than ischemic stroke. The therapeutic interventions that are currently available focus mainly on supportive care and secondary prevention. There is a paucity of evidence to support any one acute intervention that improves functional outcome. This chapter highlights current treatment targets for ICH based on the pathophysiology of the disease.

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“…64 Similarly, statin treatment has been shown to improve outcomes in murine models of intracranial hemorrhage 65,66 and acute ischemic stroke. [67][68][69] …”

Section: Preclinical Models Of Acute Brain Injurymentioning

confidence: 99%

Statins in Traumatic Brain Injury

Wible

Laskowitz

2010

Neurotherapeutics

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Summary: Traumatic brain injury (TBI) is a common cause of long-term neurological morbidity, with devastating personal and societal consequences. At present, no pharmacological intervention clearly improves outcomes, and therefore a compelling unmet clinical need remains. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or "statins," offer a potential novel therapeutic strategy for TBI. Statins are well tolerated, easy to administer, and have a long clinical track record in critically ill patients. Their side effects are well defined and easily monitored. Preclinical studies have shown significant benefit of statins in models of TBI and related disease processes, including cerebral ischemia, intracerebral hemorrhage, and subarachnoid hemorrhage. In fact, multiple mechanisms have been defined by which statins may exert benefit after acute brain injury. Statins are currently positioned to be translated into clinical trials in acute brain injury and have the potential to improve outcomes after TBI.

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Treatment With Statins After Induction of Focal Ischemia in Rats Reduces the Extent of Brain Damage

Cited by 178 publications

References 40 publications

Statins and Stroke

Statins and Stroke

Treatment Targets in Intracerebral Hemorrhage

Statins in Traumatic Brain Injury

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