Rodent Models of Global Cerebral Ischemia: A Comparison of Two-Vessel Occlusion and Four-Vessel Occlusion

McBean, Douglas E.; Kelly, Paul A.

doi:10.1016/s0306-3623(97)00284-x

Cited by 53 publications

(39 citation statements)

References 27 publications

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“…Previous iterations of the 2VO global ischemia model have included a single arterial line for both inducing hemorrhage and measuring mean arterial pressure (MAP), a venous line for controlled hemorrhage along with an arterial line, and pharmacological reduction of blood pressure (McBean et al, 1998). We used dual (bilateral) femoral arterial lines in this study.…”

Section: Discussionmentioning

confidence: 99%

The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

Matchett¹,

Calinisan²,

Matchett³

et al. 2007

Brain Research

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Granulocyte-colony stimulating factor (G-CSF) is an endogenous peptide hormone of the hematopoietic system that has entered Phase I/II clinical trials for treatment of ischemic stroke. Severe intraoperative hypotension can lead to global cerebral ischemia and apoptotic neuron loss within the hippocampus. We tested G-CSF in a rat model of global cerebral ischemia. Global cerebral ischemia was induced in male Sprague-Dawley rats (280-330g) with the 2-vessel occlusion model (hemorrhagic hypotension to a mean arterial pressure of 30-35 mmHg and bilateral common carotid artery occlusion for 8 minutes). Three groups of animals were used: global ischemia without treatment (GI, n=49), global ischemia with G-CSF treatment (GI+G-CSF, n=42), and sham surgery (Sham, n = 26). Rats in the treatment group received G-CSF (50 μg / kg, subcutaneously) 12 hours before surgery, on the day of surgery, and on post-operative Day 1, and were euthanized on Day 2, 3, and 14. Mild hyperglycemia was observed in all groups. T-maze testing for spontaneous alternation demonstrated initial improvement in the G-CSF treatment group but no long-term benefit. Measurement of daily body weight demonstrated an initial trend toward improvement in the G-CSF group. Quantitative Nissl histology of the hippocampus demonstrated equivalent outcomes on Day 3 and 14, which was supported by quantitative TUNEL stain. Immunohistochemistry and Western blot demonstrated an initial increase in phosphorylated-AKT in the GI+G-CSF group on Day 2. We conclude that G-CSF treatment is associated with transient early improvement in neurobehavioral outcomes after global ischemia complicated by mild hyperglycemia, but no long-term protection.

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Section: Discussionmentioning

confidence: 99%

The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

Matchett¹,

Calinisan²,

Matchett³

et al. 2007

Brain Research

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“…The classical two-vessel occlusion model performed in rats is accompanied by either hypoxia or hypotension to attenuate cerebral ischemia, by preventing collateral blood supply to the forebrain during the procedure [2,[4][5][6]. To assess the effects of systemic hyperglycemia in exclusivity, a modified two-vessel occlusion model was employed, anesthetizing fed-state rats with a Ketamine/Xylazine combination, without inducing hypoxia or hypotension.…”

Section: Methodsmentioning

confidence: 99%

“…Various mechanisms of stroke induction are available; including focal and global models performed in either a permanent or transient manner [1]. The major advantages of incomplete global over focal ischemic models are that the length of ischemia is a great deal shorter and achievement of repeatability is more successful [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…This model is relevant in ischemia caused by disease states such as diabetes and atherosclerosis, as well as in traumatic brain injury [7]. Two-vessel occlusion without hypotension or hypoxia, however, is neither sufficient to bring cerebral blood flow down below the ischemic threshold, nor to upset the brain's energy state enough to produce quantifiable cell death [4][5][6]. Rats possess a posterior communicating artery and a complete circle of Willis [2], therefore posterior circulation will compensate for anterior occlusion up to a certain threshold.…”

Section: Introductionmentioning

confidence: 99%

“…Rats possess a posterior communicating artery and a complete circle of Willis [2], therefore posterior circulation will compensate for anterior occlusion up to a certain threshold. For this reason either blood flow or oxygenation of blood has to be reduced at the same time that the carotid arteries are occluded in order to produce quantifiable neural injury [4][5][6]. It is clearly understood that hyperglycemia (as in diabetes) intensifies the outcome of cerebral ischemia in both focal and global cerebral ischemic models [8,9].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Hyperglycemic Modification to Classical Two-Vessel Occlusion for Inducing Transient Cerebral Ischemia in Sprague-Dawley Rats

Spuy

Goosen²,

Bosman³

2015

Journal of Neurophysiology and Neurological Disorders

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Cerebral ischemia is widely studied through the employment of experimental animal models. Incomplete global models such as two-vessel occlusion are relevant in the study of disease states which may attenuate cerebral ischemia. Hyperglycemia is known to worsen the consequences of ischemia but has not been exclusively employed. The two-vessel occlusion model, which is unsuccessful when employed in the absence of hypotension and/or hypoxia, is thus ideal for modification to a hyperglycemic model. We therefore describe an established technique for inducing hyperglycemic cerebral ischemia through modification of the two-vessel occlusion model as well as the procedure subsequently used to confirm cerebral injury. This method produces a larger degree of neural injury in males than in females, with estradiol levels negatively correlated to neural injury, confirming trends in research where estrogen is shown to be neuroprotective. Overall, this data is consistent with findings obtained by other groups, showing the neuroprotective nature of endogenous estradiol in rat models, with cyclic female animals sustaining less neural injury than age-matched male and acyclic female counterparts Furthermore, this technique proves to be simple, highly repeatable and cost effective. In conclusion, the hyperglycemic cerebral ischemia model developed as a modification to the two-vessel occlusion model (with exclusion of hypoxia and/or hypotension) proved successful for the study of cerebral ischemia.

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Animal models of stroke

Zhang

2021

Anim Models and Exp Med

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Stroke is a leading cause of morbidity and mortality worldwide and in China. In China, stroke was the leading cause of death and DALYs in 2017. 1 Age-standardized DALYs per 100 000 population decreased by 33.1% for stroke. Of all strokes, up to 80% to 85% are ischemic, 2 which can be subdivided based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. 3 Large vessel atherosclerosis of cervical or proximal intracranial vessels comprises a major cause of acute stroke, ranging from 30% to 43%, while 20%-31% is caused by cardioembolism. Approximately 10%-23% of all strokes are lacunar in type, which are mainly caused by diabetes and hypertension. Some additional unusual causes, such as vasculopathy or extracranial artery dissection, account for 2%-11%. 4,5 Approximately 5%-21% of strokes are hemorrhagic, and their common causes are hypertension and vascular malformations. 6 Strokes are heterogeneous diseases, and in vivo models are essential tools to mimic these processes for investigating pathophysiology and therapeutic approaches. Each model has its unique strengths and weaknesses (Tables 1 and 2). Only when we realize their importance can we choose the best one for an investigation, with "best" referring to that which most closely approximates a certain aspect of the multiple facets of strokes.

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Rodent Models of Global Cerebral Ischemia: A Comparison of Two-Vessel Occlusion and Four-Vessel Occlusion

Cited by 53 publications

References 27 publications

The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

The effect of granulocyte-colony stimulating factor in global cerebral ischemia in rats

Hyperglycemic Modification to Classical Two-Vessel Occlusion for Inducing Transient Cerebral Ischemia in Sprague-Dawley Rats

Animal models of stroke

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