Focal Ischemia Models: Middle Cerebral Artery Occlusion Induced by Electrocoagulation, Occluding Devices, and Endothelin
This chapter covers established rodent models of middle cerebral artery occlusion (MCAO), where ischemia is induced by electrocoagulation of the artery, occluding devices applied to the artery, or application of the peptide endothelin-1 to the artery to i
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1. Introduction Models of MCA occlusion (MCAO) were first developed in primates in the 1930s (1) and later refined and scaled down for use in rodents in the 1970s and early 1980s (2, 3). The subtemporal approach with MCAO by electrocoagulation, published by Akira Tamura and colleagues in Glasgow, has emerged as the standard method for permanent proximal MCAO in rats and has been cited over 990 times since its publication in 1981. Its success is based on reproducible ischemia, infarction, and low mortality. Cerebral blood flow (CBF) is reduced to below 25 ml 100 g−1 min−1 within MCA territory, ischemic damage is evident within cortex
Ulrich Dirnagl (ed.), Rodent Models of Stroke, Neuromethods, vol. 47, DOI 10.1007/978-1-60761-750-1_5, © Springer Science+Business Media, LLC 2010
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and dorsolateral striatum by 4 h post-occlusion, and infarct size is maximal by 24 h. Subsequent variations in the model include (1) restricting infarction to the cortex by sparing the lenticulostriate branches and applying electrocoagulation more distally (4). This variation is also less technically demanding; (2) Tandem occlusion of the MCA and ipsilateral common carotid artery (ICCAO) to improve reproducibility of infarction (5, 6); (3) replacing electrocoagulation with occluding devices, such as microaneurysm clips, hooks, or ligature snares (7–9), which in addition provide the opportunity to induce transient ischemia of defined duration followed by reperfusion; (4) replacing electrocoagulation with application of the peptide endothelin-1 to induce vasospasm (10–12). The size and reproducibility of infarction induced by the original Tamura model has also been investigated in aged versus adult rats, and in different strains, including those with recognized stroke risk factors such as the spontaneously hypertensive rat, spontaneously hypertensive stroke-prone rat, and the streptozotocin-induced diabetic rat (13); This chapter provides an overview of these models and the basic equipment and consumables needed to set them up.
2. Equipment and Materials 2.1. Laboratory Equipment
1. A good operating microscope is essential when setting up rodent stroke models which require surgical exposure of the MCA (see Note 1). 2. Equipment is required for sterilizing surgical instruments (e.g., autoclave). In some labs, I have seen commercial equipment designed for sterilizing dental tools or hairdressers scissors used. When operating on a number of animals in a single session, tips of instruments can be sterilized with bench top glass bead sterilizers (instrument tips should be cleaned, then inserted into the heated beads (>200°C) for ~15 s, allowing time to cool before contacting tissues). 3. Homeothermic heating blanket (e.g., Harvard) or thick cork board (RA Lamb, London, UK) and heating lamp to maintain body temperature under anesthesia. Extra vigilance is required when using heating lamps to avoid the possibility of overheating. 4. Rectal temperature recording system (e.g., Physitemp). Fine needle probes for insertion into tempora
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