The Validity of Rodent Brain-Ischemia Models Is Self-evident

Ginsberg, Myron D.

doi:10.1001/archneur.1996.00550100151024

Cited by 36 publications

(10 citation statements)

References 41 publications

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“…The first focus is experimental design. Although there is a significant debate regarding animal models that should be used for translational research, [10][11][12][13][14][15][16][17][18][19] patient population data show that ischemic stroke is heterogeneous with some patients pre senting with small lacunar strokes and cardioembolic strokes with others. [20][21][22][23] Nevertheless, the investigator must clearly define the rationale for the selected models and end points to be studied.…”

Section: Recommendations For Study Design and Reportingmentioning

confidence: 99%

Recommendations and Practices to Optimize Stroke Therapy

Lapchak

2013

Stroke

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Section: Recommendations For Study Design and Reportingmentioning

confidence: 99%

Recommendations and Practices to Optimize Stroke Therapy

Lapchak

2013

Stroke

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“…Therefore, it is only rational to use an animal model of stroke that closely mirrors human stroke, a model that is based on embolization. Historically, the standard stroke model used in academia and industry is the middle cerebral occlusion model in the rat [175]. However, as is clear from the development profile of NXY-059 and many other neuroprotective drugs that have failed in clinical trials, the rodent model is inadequate for the development of neuroprotective drugs to treat stroke.…”

Section: Are Neuroprotective Strategies and Clinical Trials Warranted?mentioning

confidence: 99%

Advances in ischemic stroke treatment: neuroprotective and combination therapies

Lapchak

Araujo

2007

Expert Opinion on Emerging Drugs

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Thrombolysis with intravenous alteplase (recombinant tissue-type plasminogen activator) continues to be the sole recourse for acute ischemic stroke therapy, provided that patients seek treatment preferably within 3 h of stroke onset. The narrow window of efficacy, coupled with the significant risk of hemorrhage and the high mortality rate, preclude the use of alteplase beyond this time frame. Moreover, in part because of safety concerns, only a small percentage (6-15%) of eligible patients is treated with alteplase. Clearly, safer and more effective treatments that focus on improving the shortcomings of the present thrombolysis for stroke need to be identified. Therefore, newer thrombolytics are being developed with the goal of minimizing side effects, while also shortening the time of cerebral reperfusion and extending the therapeutic window of efficacy. Besides thrombolytics, new and potentially useful drugs and devices are also being studied either as monotherapeutic agents or for use in conjunction with alteplase. In animal models of stroke, neuroprotective agents that affect various components of the ischemic injury cascade that results in neurodegeneration have shown promise for the latter. Examples of such agents include spin traps that block oxidative stress, metalloprotease inhibitors that prevent vascular damage, anti-inflammatory drugs that suppress inflammation and transcranial infrared laser irradiation, which promotes recovery of function. Ideally, a successful combination of neuroprotectant (drug or device) and thrombolytic therapy for stroke would minimize the side effects of thrombolysis followed by supplementary neuroprotection thereafter.

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“…Nevertheless, the relevance of animal stroke models is reasonably evident, as discussed by Ginsberg. 1 In particular, rodent models have crucial advantages of lower cost, suitability for physiological monitoring, reproducibility of lesion size, and ease of conducting replicate studies. Although Huang et al 2 suggested that the number of animals needed to demonstrate a 50% decrease in infarction volume may be reduced by 41% in their modified transorbital baboon model compared with a previous nonhuman primate stroke model, the coefficient of variation (CV) for infarct volume was still considerably large (62%).…”

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confidence: 99%

Photothrombotic Middle Cerebral Artery Occlusion and Reperfusion Laser System in Spontaneously Hypertensive Rats

Yao

Sugimori

Fukuda

et al. 2003

Stroke

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Background and Purpose-To establish a less invasive and reproducible focal ischemia model in the rat, we adopted a 2-laser system (ie, photothrombosis and YAG laser-induced reperfusion). Methods-The distal middle cerebral artery (MCA) of spontaneously hypertensive rats was occluded by 568-nm krypton laser and intravenous infusion of the photosensitizing dye rose bengal and was recanalized by 355-nm ultraviolet laser irradiation. Cerebral blood flow was determined by laser-Doppler flowmetry at the penumbral cortex. Infarct volume was determined at 3 days after distal MCA occlusion. Results-Brain temperature determined with infrared thermography was maintained within an acceptable range of approximately 1°C upper shift of the center of brain temperature distribution during krypton or YAG laser irradiation. The average of the values (23 experiments; nϭ163) of coefficient of variation of infarct volume was 21Ϯ6%, indicating high reproducibility of this model. After distal MCA occlusion, cerebral blood flow was decreased to 32Ϯ16% of the control values and was increased to 98Ϯ21% after YAG laser-induced reperfusion. Infarct volume in these rats was 61Ϯ18 mm 3 (coefficient of variationϭ30%; nϭ6). Conclusions-We have characterized a highly reproducible focal ischemia model utilizing a 2-laser system, one to induce thrombotic MCA occlusion and the other to facilitate reperfusion.

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The Validity of Rodent Brain-Ischemia Models Is Self-evident

Cited by 36 publications

References 41 publications

Recommendations and Practices to Optimize Stroke Therapy

Recommendations and Practices to Optimize Stroke Therapy

Advances in ischemic stroke treatment: neuroprotective and combination therapies

Photothrombotic Middle Cerebral Artery Occlusion and Reperfusion Laser System in Spontaneously Hypertensive Rats

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