Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats

Seyfried, Donald; Han, Yu; Lu, Dunyue; Chen, Jieli; Bydon, Ali; Chopp, Michael

doi:10.3171/jns.2004.101.1.0104

Cited by 120 publications

(107 citation statements)

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“…As an experimental model, the direct injection of autologous blood into the striatum in the rat has proven reliable for studying the pathophysiological changes occurring after spontaneous ICH (Seyfried et al, 2004). In the ICH model of injury we have demonstrated that MSCs localize around the ICH and that features of active neuroregeneration are present after intravenous administration of 3-8 million cells (Seyfried et al, 2006).…”

Section: Discussionmentioning

confidence: 87%

Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage

et al. 2008

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Previous studies show that intravascular injection of human bone marrow stromal cells (hBMSCs) significantly improves neurological functional recovery in a rat model of intracerebral hemorrhage (ICH). In the present study, we tested the hypothesis that mannitol improves the efficiency of intraarterial MSC delivery (i.e., fewer injected cells required for therapeutic efficacy) after ICH. There were four post-ICH groups (N=9): group 1, negative control with only intra-arterial injection of 1 million human fibroblasts in phosphate-buffered saline (PBS); group 2, intravenous injection of mannitol alone in PBS (1.5 g/kg); group 3, intra-arterial injection of 1 million hBMSCs alone in PBS; and group 4, intravenous injection of mannitol (1.5 g/kg) in PBS followed by intra-arterial injection of 1 million hBMSCs in PBS. Group 4 exhibited significantly improved neurological functional outcome as assessed by neurological severity score (NSS) and corner test scores. Immunohistochemical staining of group 4 suggested increased synaptogenesis, proliferating immature neurons, and neuronal migration. The number of hBMSCs recruited to the injured region increased strikingly in group 4. Tissue loss was notably reduced in group 4. In summary, the beneficial effects of intra-arterial infusion of MSCs are amplified with intravenous injection of mannitol. Preadministration of mannitol significantly increases the number of hBMSCs located in the ICH region, improves histochemical parameters of neural regeneration, and reduces the anatomical and pathological consequences of ICH.

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Section: Discussionmentioning

confidence: 87%

Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage

et al. 2008

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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]. Atorvastatin reduced perihematoma cell death via an anti-inflammatory mechanism and this was also associated with sensorimotor recovery [129].…”

Section: Anti-inflammatory Agents: Statinsmentioning

confidence: 97%

“…The neurological improvement became apparent at 1 week and was consistent throughout 4 weeks. In addition, the statins increased cell proliferation and differentiation suggesting that enhanced neuroplasticity may be the mechanism for improved function [128,130].…”

Section: Anti-inflammatory Agents: Statinsmentioning

confidence: 99%

“…For example, 2 groups have demonstrated an effect of statins on hematoma volume [128,130], whereas another group has not [129]. Thus far, preclinical studies demonstrate an effect on hematoma volume, brain atrophy, hemispheric water content, and neurologic function; however, clinical evaluation of the statins has been limited to a demonstration of associations between statin use and mortality, and perihematomal edema.…”

Section: Anti-inflammatory Agents: Statinsmentioning

confidence: 99%

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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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“…The most compelling preclinical data is in experimental SAH, where statins have been demonstrated to reduce vasospasm and improve outcomes after SAH in the mouse, 39,60 rat, 61,62 rabbit, 39,63 and dog. 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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Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats

Abstract: Analysis of the data in this study indicates that atorvastatin improves neurological recovery after experimental ICH and may do so in part by increasing neuronal plasticity.

Cited by 120 publications

References 20 publications

Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage

Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage

Treatment Targets in Intracerebral Hemorrhage

Statins in Traumatic Brain Injury

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