Middle Cerebral Artery Occlusion Model in Rodents: Methods and Potential Pitfalls

Liu, Fudong; McCullough, Louise D.

doi:10.1155/2011/464701

Cited by 181 publications

(162 citation statements)

References 85 publications

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“…have examined middle aged and aging animals, and these have led to somewhat inconsistent results (Liu and McCullough, 2011). This might partly explain the translational failure of neuroprotective drugs in humans.…”

Section: Dha-alb Therapy Provides Neuroprotection After Stroke In Agementioning

confidence: 99%

A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

Belayev

Khoutorova

Hong

et al. 2015

OCL

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-Despite tremendous efforts in ischemic stroke research and significant improvements in patient care within the last decade, therapy is still insufficient. There is a compelling, urgent need for safe and effective neuroprotective strategies to limit brain injury, facilitate brain repair, and improve functional outcome. Recently, we reported that docosahexaenoic acid (DHA; 22:6, n-3) complexed to human albumin (DHA-Alb) is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo) in young rats. This review highlights the potency of DHA-Alb therapy in permanent MCAo and aged rats and whether protection persists with chronic survival. We discovered that a novel therapy with DHA-Alb improved behavioral outcomes accompanied by attenuation of lesion volumes even when animals were allowed to survive three weeks after experimental stroke. This treatment might provide the basis for future therapeutics for patients suffering from ischemic stroke.Keywords: Omega-3 polyunsaturated fatty acids / neuroprotection / behavior / MRI / histopathology Résumé -Une nouvelle stratégie thérapeutique pour les AVC expérimentaux utilisant l'acide docosahexaénoïque complexé à l'albumine humaine. En dépit des avancées de la recherche sur l'AVC ischémique et des amé-liorations significatives des soins apportés aux patients durant la dernière décennie, la thérapie de prise en charge demeure encore insuffisante. Ainsi, il est urgent de développer des stratégies neuroprotectrices sûres et efficaces afin de limiter le développement des lésions cérébrales et de restaurer les altérations cellulaires et fonctionnelles. Récemment, nous avons mis en évidence que l'acide docosahexaénoïque (DHA ; 22:6, n-3) complexé à l'albumine humaine (DHAAlb) s'avère hautement neuroprotecteur chez le jeune rat après une occlusion cérébrale moyenne temporaire de l'artère (MCAo). Cette revue met en avant tout le potentiel d'une thérapie DHA-Alb chez des rats MCAo permanents et âgés, et soulève la question de la persistance de la neuroprotection en condition de survie prolongée. Cette nouvelle théra-pie de traitement avec du DHA-Alb améliore par ailleurs les performances comportementales et s'accompagne d'une régression volume des lésions cérébrales même après 3 semaines suivant l'AVC expérimental. Ce type de traitement pourrait ainsi constituer une nouvelle base de prise en charge des patients atteints d'un AVC ischémique.Mots clés : Oméga-3 / acides gras poly-insaturés / neuroprotection / comportement / IRM / histopathologie

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Section: Dha-alb Therapy Provides Neuroprotection After Stroke In Agementioning

confidence: 99%

A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

Belayev

Khoutorova

Hong

et al. 2015

OCL

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“…The majority of events are initiated by the formation of an embolic or thrombotic occlusion at or near the middle cerebral artery (MCA). Given these parameters, the model presented closely mimics disease etiology of human stroke and makes results obtained highly relevant 3 . Nevertheless, the translation of discoveries from animal models to disease treatment in humans has proven to be challenging.…”

Section: Introductionmentioning

confidence: 99%

Induction of Ischemic Stroke and Ischemia-reperfusion in Mice Using the Middle Artery Occlusion Technique and Visualization of Infarct Area

Bertrand

Dygert

Toborek

2017

JoVE

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Cerebrovascular disease is highly prevalent in the global population and encompasses several types of conditions, including stroke. To study the impact of stroke on tissue injury and to evaluate the effectiveness of therapeutic interventions, several experimental models in a variety of species were developed. They include complete global cerebral ischemia, incomplete global ischemia, focal cerebral ischemia, and multifocal cerebral ischemia. The model described in this protocol is based on the middle cerebral artery occlusion (MCAO) and is related to the focal ischemia category. This technique produces consistent focal ischemia in a strictly defined region of the hemisphere and is less invasive than other methods. The procedure described is performed on mice, given the availability of several genetic variants and the high number of tests standardized for mice to aid in the behavioral and neurodeficit evaluation.

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“…Since many biochemical parameters decrease with aging (Sinha et al 2005;Bala et al 2006;Arumugam et al 2010;Liu and McCullough 2011;, it would expect a lessened ability of response to the stroke. However, age-dependent differences in the time-course of the stroke-induced response of different molecules could play crucial roles in the discovery of new therapeutic targets or therapies (Anyanwu 2007).…”

mentioning

confidence: 99%

Age-dependent modifications in vascular adhesion molecules and apoptosis after 48-h reperfusion in a rat global cerebral ischemia model

Anuncibay‐Soto

Pérez‐Rodríguez

Llorente

et al. 2014

AGE

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Stroke is one of the leading causes of death and permanent disability in the elderly. However, most of the experimental studies on stroke are based on young animals, and we hypothesised that age can substantially affect the stroke response. The two-vessel occlusion model of global ischemia by occluding the common carotid arteries for 15 min at 40 mmHg of blood pressure was carried out in 3-and 18-month-old male Sprague-Dawley rats. The adhesion molecules E-and P-selectin, cell adhesion molecules (CAMs), both intercellular (ICAM-1) and vascular (VCAM-1), as well as glial fibrillary acidic protein (GFAP), and cleaved caspase-3 were measured at 48 h after ischemia in the cerebral cortex and hippocampus using Western blot, qPCR and immunofluorescence techniques. Diametric expression of GFAP and a different morphological pattern of caspase-3 labelling, although no changes in the cell number, were observed in the neurons of young and old animals. Expression of E-selectin and CAMs was also modified in an age-and ischemia/reperfusiondependent manner. The hippocampus and cerebral cortex had similar response patterns for most of the markers studied. Our data suggest that old and young animals present different time-courses of neuroinflammation and apoptosis after ischemic damage. On the other hand, these results suggest that neuroinflammation is dependent on age rather than on the different vulnerability described for the hippocampus and cerebral cortex. These differences should be taken into account in searching for therapeutic targets.

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Middle Cerebral Artery Occlusion Model in Rodents: Methods and Potential Pitfalls

Cited by 181 publications

References 85 publications

A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

A novel therapeutic strategy for experimental stroke using docosahexaenoic acid complexed to human albumin

Induction of Ischemic Stroke and Ischemia-reperfusion in Mice Using the Middle Artery Occlusion Technique and Visualization of Infarct Area

Age-dependent modifications in vascular adhesion molecules and apoptosis after 48-h reperfusion in a rat global cerebral ischemia model

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