Abstract
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 induce vasospasm. Electrocoagulation induces a permanent occlusion of the artery, but the other models can be modified to induce permanent or transient MCAO.
All of the models involve some degree of cranial surgery, so the importance of aseptic technique is highlighted as is the importance of monitoring and maintaining the animals’ physiology under anesthesia. Mortality rates are generally low in models which require a craniectomy. Since these models are used for both short- and long-term survival studies, some details of postoperative care are also included.
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References
Peterson JN, Evans JP (1937) The anatomical end results of cerebral artery occlusion: an experimental and clinical correlation. Trans Am Neurol Assoc 63:83–88
Robinson RG, Shoemaker WJ, Schlump M, Valk T, Bloom FE (1975) Effect of experimental cerebral infarction in rat brain on catecholamines and behaviour. Nature 255:332–334
Tamura A, Graham DI, McCulloch J, Teasdale GM (1981) Focal cerebral ischemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1:53–60
Shigeno T, McCulloch J, Graham DI, Mendelow AD, Teasdale GM (1985) Pure cortical ischemia versus striatal ischemia. Surg Neurol 24:47–51
Chen S, Hsu CY, Hogan EL, Maricq H, Balentine JD (1986) A model of focal ischemic stroke in the rat: reproducible extensive cortical infarction. Stroke 17:738–743
Brint S, Jacewicz M, Kiessling M, Tanabe J, Pulsinelli W (1988) Focal brain ischemia in the rat: methods for reproducible neocortical infarction using tandem occlusion of the distal middle cerebral and ipsilateral common carotid arteries. J Cereb Blood Flow Metab 8:474–485
Dietrich WD, Nakayama H, Watson BD, Kanemitsu H (1989) Morphological consequences of early reperfusion following thrombotic or mechanical occlusion of the rat middle cerebral artery. Acta Neuropath 78:605–614
Kaplan B, Brint S, Tanabe J, Jacewicz M, Wang X-J, Pulsinelli W (1991) Temporal thresholds for neocortical infarction in rats subjected to reversible focal cerebral ischemia. Stroke 22:1032–1039
Shigeno T, Teasdale GM, McCulloch J, Graham DI (1985) Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability and brain edema. J Neurosurg 63:272–277
Morancho A, GarcĂa-Bonilla L, BarcelĂł V, Giralt D, Campos-Martorell M, Garcia S, Montaner J, Rosell A (2012) A new method for focal transient cerebral ischaemia by distal compression of the middle cerebral artery. Neuropathol Appl Neurobiol 38:617–627
Fuxe K, Kurosawa N, Cintra A, Hallstrom A, Goiny M, Rosen L, Agnati LF, Ungerstedt U (1992) Involvement of local ischemia in endothelin-1 induced lesions of the neostriatum of the anaesthetized rat. Exp Brain Res 88:131–139
Macrae IM, Robinson MJ, Graham DI, Reid JL, McCulloch J (1993) Endothelin induced reductions in cerebral blood flow: dose-dependency, time course and neuropathological consequences. J Cereb Blood Flow Metab 13:276–284
Sharkey J, Ritchie IM, Kelly PAT (1993) Perivascular microapplication of endothelin-1: a new model of focal cerebral ischemia in the rat. J Cereb Blood Flow Metab 13:865–871
Duverger D, Mackenzie ET (1988) The quantification of cerebral infarction following focal ischemia in the rat: influence of strain arterial pressure blood glucose concentration and age. J Cereb Blood Flow Metab 8:449–461
Robinson RG, Coyle JT (1980) The differential effect of right versus left hemispheric cerebral infarction on catecholamines and behaviour in the rat. Brain Res 188:63–78
Wayman C, Duricki DA, Roy L, Haenzi B, Tsai S-Y, Kartje G, Beech J, Cash D, Moon L (2015) Performing permanent distal middle cerebral with common carotid artery occlusion in aged rats to study cortical ischemia with sustained disability. J Vis Exp. doi:10.3791/53106
Llovera G, Roth S, Plesnila N, Veltkamp R, Liesz A (2014) Modeling stroke in mice: permanent coagulation of the distal middle cerebral artery. J Vis Exp (89):e51729. doi:10.3791/51729
Colak G, Filiano AJ, Johnson GV (2011) The application of permanent middle cerebral artery ligation in the mouse. J Vis Exp (53):e3039. doi:10.3791/3039
Ansari S, Azari H, Caldwell KJ, Regenhardt RW, Hedna VS, Waters MF et al (2013) Endothelin-1 induced middle cerebral artery occlusion model for ischemic stroke with laser doppler flowmetry guidance in rat. J Vis Exp (72):e50014. doi:10.3791/50014
Regenhardt RW, Ansari S, Azari H, Caldwell KJ, Mecca AP (2013) Utilizing a cranial window to visualize the middle cerebral artery during endothelin-1 induced middle cerebral artery occlusion. J Vis Exp (72):e50015. doi:10.3791/50015
Backhauss C, Karkoutly C, Welsch M, Krieglstein J (1992) A mouse model of focal cerebral ischemia for screening neuroprotective drug effects. J Pharmacol Toxicol Methods 27:27–32
Bullock R, Graham DI, Chen MH, Lowe D, McCulloch J (1990) Focal cerebral ischemia in the cat: pre-treatment with a competitive NMDA receptor antagonist, D-CPP-ene. J Cereb Blood Flow Metab 10:668–674
Imai H, Konno K, Nakamura M, Shimizu T, Kubota C, Seki K, Honda F, Tomisawa S, Tanaka Y, Hata H, Saito N (2006) A new model of focal cerebral ischemia in the miniature pig. J Neurosurg 104:123–132
Buchan AM, Xue D, Slivka A (1992) A new model of temporary focal neocortical ischemia in the rat. Stroke 23:273–279
van Bruggen N, Thibodeaux H, Palmer JT, Lee WP, Fu L, Cairns B, Tumas D, Gerlai R, Williams SP, van Lookeren Campagne M, Ferrara N (1999) VEGF antagonism reduces edema formation and tissue damage after ischemia/reperfusion injury in the mouse brain. J Clin Invest 104:1613–1620
Robinson MJ, McCulloch J (1990) Contractile responses to endothelin in feline cortical vessels in situ. J Cereb Blood Flow Metab 10:285–289
Virley D, Hadingham SJ, Roberts JC, Farnfield B, Elliott H, Whelan G, Golder J, David C, Parsons AA, Hunter AJ (2004) A new primate model of focal stroke: endothelin-1-induced middle cerebral artery occlusion and reperfusion in the common marmoset. J Cereb Blood Flow Metab 24:24–41
Frost SB, Barbay S, Mumert ML, Stowe AM, Nudo RJ (2006) An animal model of capsular infarct: endothelin-1 injections in the rat. Behav Brain Res 169:206–211
Lecrux C, McCabe C, Weir CJ, Gallagher L, Mullin J, Touzani O, Muir KW, Lees KR, Macrae IM (2008) Effects of magnesium treatment in a model of internal capsule lesion in spontaneously hypertensive rats. Stroke 39:448–454
Acknowledgments
The author wishes to thank Drs Hilary Carswell, Hideaki Imai, Chris McCabe, John Sharkey and Mrs. Lindsay Gallagher for help and advice in preparing this chapter.
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Macrae, I.M. (2016). Focal Ischemia Models: Middle Cerebral Artery Occlusion Induced by Electrocoagulation, Occluding Devices, and Endothelin-1. In: Dirnagl, U. (eds) Rodent Models of Stroke. Neuromethods, vol 120. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-5620-3_5
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DOI: https://doi.org/10.1007/978-1-4939-5620-3_5
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