Reduction of Cerebral Infarction in Stroke-Prone Spontaneously Hypertensive Rats by Statins Associated With Amelioration of Oxidative Stress

Nagotani, Shoko; Hayashi, Takeshi; Satô, Keiko; Zhang, Wenri; Deguchi, Kentaro; Nagano, Isao; Shoji, Mikio; Abe, Kōji

doi:10.1161/01.str.0000155732.27333.3c

Cited by 61 publications

(43 citation statements)

References 9 publications

(9 reference statements)

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“…8-hydroxyguanosine (8-OHG) is a reliable and commonly used biomarker for oxidative DNA damage caused by superoxide anion, as shown previously after various forms of brain injury [27][28][29], including ICH [28,30]. Here, 8-OHG-positive cells were detected around the injury site 24 h post-ICH in WT and Nrf2 −/− mice (Fig.…”

Section: Nrf2 Deletion Increases Leukocyte Infiltrationsupporting

confidence: 64%

Role of Nrf2 in protection against intracerebral hemorrhage injury in mice

Wang

Fields

Zhao

et al. 2007

Free Radical Biology and Medicine

199

177

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Nrf2 is a key transcriptional factor for antioxidant response element (ARE)-regulated genes. While its beneficial role has been described for stroke, its contribution to intracerebral hemorrhage (ICH)-induced early brain injury remains to be determined. Using wildtype (WT) and Nrf2 knockout (Nrf2 −/− ) mice, the role of Nrf2 in ICH induced by intracerebral injection of collagenase was investigated. The results showed that injury volume was significantly larger in Nrf2 −/− mice than in WT controls 24 h after induction of ICH (p < 0.05), an outcome that correlated with neurological deficits. This exacerbation of brain injury in Nrf2 −/− mice was also associated with an increase in leukocyte infiltration, production of reactive oxygen species, DNA damage, and cytochrome c release during the critical early phase of the post-ICH period. In combination, these results suggest that Nrf2 reduces ICH-induced early brain injury, possibly by providing protection against leukocyte-mediated free radical oxidative damage.

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Section: Nrf2 Deletion Increases Leukocyte Infiltrationsupporting

confidence: 64%

Role of Nrf2 in protection against intracerebral hemorrhage injury in mice

Wang

Fields

Zhao

et al. 2007

Free Radical Biology and Medicine

199

177

View full text Add to dashboard Cite

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“…Anti-platelet agents were beneficial in ET-1-evoked infarction (Whitehead et al, 2005a) and in SHR-SP spontaneous strokes (Banfi et al, 2004), in accord with a modest beneficial effect in human lacunar stroke. Lipid-decreasing statin drugs had a beneficial effect on stroke incidence and vessel damage in SHR-SP (Kawashima et al, 2003;Nagotani et al, 2005;Sironi et al, 2005), in keeping with the secondary preventive effect of statins in lacunar stroke.…”

Section: Intervention Studies: Comparison With Human Datasupporting

confidence: 64%

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

Hainsworth

Markus

2008

J Cereb Blood Flow Metab

227

204

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Cerebral small vessel disease (SVD) is a major cause of stroke and dementia. Pathologically, three lesions are seen: small vessel arteriopathy, lacunar infarction, and diffuse white matter injury (leukoaraiosis). Appropriate experimental models would aid in understanding these pathologic states and also in preclinical testing of therapies. The objective was to perform a systematic review of animal models of SVD and determine whether these resemble four key clinicopathologic features: (1) small, discrete infarcts; (2) small vessel arteriopathy; (3) diffuse white matter damage; (4) cognitive impairment. Fifteen different models were included, under four categories: (1) embolic injuries (injected blood clot, photochemical, detergent-evoked); (2) hypoperfusion/ischaemic injury (bilateral common carotid occlusion/stenosis, striatal endothelin-1 injection, striatal mitotoxin 3-NPA); (3) hypertension-based injuries (surgical narrowing of the aorta, or genetic mutations, usually in the renin-angiotensin system); (4) blood vessel damage (injected proteases, endotheliumtargeting viral infection, or genetic mutations affecting vessel walls). Chronic hypertensive models resembled most key features of SVD, and shared the major risk factors of hypertension and age with human SVD. The most-used model was the stroke-prone spontaneously hypertensive rat (SHR-SP). No model described all features of the human disease. The optimal choice of model depends on the aspect of pathophysiology being studied.

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“…12 Similar to our findings on cilostazol, we have previously shown that statin has a pleiotropic antioxidative effect other than a direct cholesterol-lowing effect, resulting in the reduction of stroke volume. [13][14][15] In the present study, we showed a strong reduction in oxidative damage by cilostazol (Figure 4), which accounted for the reduction in spontaneous infarct volume compared with the other antiplatelet drugs (Figure 3). In CSPS 2, it was found that cilostazol is superior to aspirin for preventing stroke and reducing hemorrhagic complications with probable cerebrovascular endothelial protection.…”

Section: Omote Et Al Pleiotropic Effect Of Cilostazol In Shr-spsupporting

confidence: 59%

Clinical and Pathological Improvement in Stroke-Prone Spontaneous Hypertensive Rats Related to the Pleiotropic Effect of Cilostazol

Omote

Deguchi

Tian

et al. 2012

Stroke

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Background and Purpose-Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R). Methods-Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1R␤ expression in the hippocampus was assessed by Western blotting. Results-The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin.Only cilostazol improved motor and cognitive functions with a significant increase (PϽ0.05) in the memory-related IGF-1R-positive ratio and IGF-1R␤ expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels. Conclusions-The

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Reduction of Cerebral Infarction in Stroke-Prone Spontaneously Hypertensive Rats by Statins Associated With Amelioration of Oxidative Stress

Cited by 61 publications

References 9 publications

Role of Nrf2 in protection against intracerebral hemorrhage injury in mice

Role of Nrf2 in protection against intracerebral hemorrhage injury in mice

Doin vivoExperimental Models Reflect Human Cerebral Small Vessel Disease? a Systematic Review

Clinical and Pathological Improvement in Stroke-Prone Spontaneous Hypertensive Rats Related to the Pleiotropic Effect of Cilostazol

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