The purpose of this study was to compare acute cerebral perfusion measured by computed tomography, stroke lesion volume measured by magnetic resonance imaging, and motor function in Sprague-Dawley rats supplied by Charles River (Charles River, Quebec, Canada) and Harlan (Harlan, Michigan, USA). During the acute stages of ischemia (<3 hours), Sprague-Dawley rats supplied by Harlan had a greater reduction in blood flow (67%) than rats supplied by Charles River (37%). MRI at days 1 and 6 after ischemia showed larger lesions in the Charles River animals compared to Harlan animals ( ) at both time points. Lesion volume decreased in both Charles River and Harlan rats at day 6 compared to day 1 ( ) and corresponded to lesion size on histology. The Harlan animals had significant functional deficits ( ) one day after surgery in postural hang reflex, forelimb placement, and tactile fraction first tests, whereas rats supplied by Charles River had no significant functional impairment as a result of surgery. The current study provides evidence that differences in response to ischemia between rats of the same strain supplied by different vendors should be an important consideration when animals are selected for the study of cerebral ischemia. 1. Introduction Various focal ischemia models can be used [1–7] to evaluate potential therapies for stroke. These models typically involve occlusion of the middle cerebral artery (MCA) and are subdivided into permanent and reversible. Permanent models include the Tamura approach [4, 6, 7] and its modifications involving the use of clips and threads [8–12], cauterization, [13] or reversible snare ligature [14]. Cauterization of the MCA followed by permanent occlusion of the ipsilateral carotid artery and temporary occlusion of the contralateral carotid artery is one of the most frequently used models for focal and irreversible ischemia in rats [1–5]. This model of ischemia allows only partial reperfusion and results in a reproducible predominantly cortical insult in the primary somatosensory cortex (S1FL, S1BF) and the CA1 field of the hippocampus, without severe impairment of motor function [15]. The temporary occlusion of the contralateral carotid artery reduces cerebral blood flow to ischemic ranges. This model is typically chosen because of its low mortality rate and is used for investigations of the biochemical changes during cerebral ischemia [15]. When considering the animal model for ischemia studies, several criteria must be evaluated including the animal species and strain, as well as the animal supplier. Ischemia
J. Agulla, B. Argibay, M. Pérez-Mato, D. Brea, P. Ramos-Cabrer, and J. Castillo, “Comparison of the lesion produced by permanent focal cerebral ischaemia in three animal models using magnetic resonance imaging,” Revista de Neurologia, vol. 53, no. 5, pp. 265–274, 2011.
M. Bacigaluppi, G. Comi, and D. M. Hermann, “Animal models of ischemic stroke. Part two: modeling cerebral ischemia,” The Open Neurology Journal, vol. 4, pp. 34–38, 2010.
J. B. Casals, N. C. G. Pieri, M. L. T. Feitosa et al., “The use of animal models for stroke research: a review,” Comparative Medicine, vol. 61, no. 4, pp. 305–313, 2011.
M. J. O'Neill and J. A. Clemens, “Rodent models of global cerebral ischemia,” in Current Protocols in Neuroscience, chapter 9, unit 9.6, John Wiley & Sons, New York, NY, USA, 2001.
A. Tamura, D. I. Graham, J. McCulloch, and G. M. Teasdale, “Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion,” Journal of Cerebral Blood Flow and Metabolism, vol. 1, no. 1, pp. 53–60, 1981.
A. Tamura, D. I. Graham, J. McCulloch, and G. M. Teasdale, “Focal cerebral ischaemia in the rat: 2. Regional cerebral blood flow determined by [14C]iodoantipyrine autoradiography following middle cerebral artery occlusion,” Journal of Cerebral Blood Flow and Metabolism, vol. 1, no. 1, pp. 61–69, 1981.
H. Nagasawa and K. Kogure, “Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion,” Stroke, vol. 20, no. 8, pp. 1037–1043, 1989.
R. Prieto, F. Carceller, J. M. Roda, and C. Avenda？o, “The intraluminal thread model revisited: rat strain differences in local cerebral blood flow,” Neurological Research, vol. 27, no. 1, pp. 47–52, 2005.
T. Shigeno, G. M. Teasdale, J. McCulloch, and D. I. Graham, “Recirculation model following MCA occlusion in rats. Cerebral blood flow, cerebrovascular permeability, and brain edema,” Journal of Neurosurgery, vol. 63, no. 2, pp. 272–277, 1985.
N. Shimamura, N. Matsuda, K. Katayama, and H. Ohkuma, “Novel rat middle cerebral artery occlusion model: trans-femoral artery approach combined with preservation of the external carotid artery,” Journal of Neuroscience Methods, vol. 184, no. 2, pp. 195–198, 2009.
H. Yanamoto, I. Nagata, N. Hashimoto, and H. Kikuchi, “Three-vessel occlusion using a micro-clip for the proximal left middle cerebral artery produces a reliable neocortical infarct in rats,” Brain Research Protocols, vol. 3, no. 2, pp. 209–220, 1998.
C. Backhauss, C. Karkoutly, M. Welsch, and J. Krieglstein, “A mouse model of focal cerebral ischemia for screening neuroprotective drug effects,” Journal of Pharmacological and Toxicological Methods, vol. 27, no. 1, pp. 27–32, 1992.
T. Shigeno, J. McCulloch, D. I. Graham, A. D. Mendelow, and G. M. Teasdale, “Pure cortical ischemia versus striatal ischemia. Circulatory, metabolic, and neuropathologic consequences,” Surgical Neurology, vol. 24, no. 1, pp. 47–51, 1985.
K. Griffin, A. Polichnowski, H. Licea-Vargas et al., “Large BP-dependent and -independent differences in susceptibility to nephropathy after nitric oxide inhibition in Sprague-Dawley rats from two major suppliers,” The American Journal of Physiology, vol. 302, no. 1, pp. 173–182, 2012.
D. M. Pollock and A. Rekito, “Hypertensive response to chronic NO synthase inhibition is different in Sprague-Dawley rats from two suppliers,” The American Journal of Physiology, vol. 275, no. 5, pp. 1719–1723, 1998.
M. Langer, C. Brandt, and W. L？scher, “Marked strain and substrain differences in induction of status epilepticus and subsequent development of neurodegeneration, epilepsy, and behavioral alterations in rats,” Epilepsy Research, vol. 96, no. 3, pp. 207–224, 2011.
D. Duverger and E. T. MacKenzie, “The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age,” Journal of Cerebral Blood Flow and Metabolism, vol. 8, no. 4, pp. 449–461, 1988.
S. Kacew, R. Dixit, and Z. Ruben, “Diet and rat strain as factors in nervous system function and influence of confounders,” Biomedical and Environmental Sciences, vol. 11, no. 3, pp. 203–217, 1998.
M. Marosi, G. Rákos, H. Robotka et al., “Hippocampal (CA1) activities in Wistar rats from different vendors. Fundamental differences in acute ischemia,” Journal of Neuroscience Methods, vol. 156, no. 1-2, pp. 231–235, 2006.
V. C. Moser, K. L. McDaniel, and P. M. Phillips, “Rat strain and stock comparisons using a functional observational battery: baseline values and effects of amitraz,” Toxicology and Applied Pharmacology, vol. 108, no. 2, pp. 267–283, 1991.
H. S. Oliff, E. Weber, G. Eilon, and P. Marek, “The role of strain/vendor differences on the outcome of focal ischemia induced by intraluminal middle cerebral artery occlusion in the rat,” Brain Research, vol. 675, no. 1-2, pp. 20–26, 1995.
H. S. Oliff, E. Weber, B. Miyazaki, and P. Marek, “Infarct volume varies with rat strain and vendor in focal cerebral ischemia induced by transcranial middle cerebral artery occlusion,” Brain Research, vol. 699, no. 2, pp. 329–331, 1995.
S. Palm, E. Roman, and I. Nylander, “Differences in voluntary ethanol consumption in Wistar rats from five different suppliers,” Alcohol, vol. 45, no. 6, pp. 607–614, 2011.
H. S. Oliff, P. Coyle, and E. Weber, “Rat strain and vendor differences in collateral anastomoses,” Journal of Cerebral Blood Flow and Metabolism, vol. 17, no. 5, pp. 571–576, 1997.
A. Cenic, D. G. Nabavi, R. A. Craen, A. W. Gelb, and T.-Y. Lee, “Dynamic CT measurement of cerebral blood flow: a validation study,” The American Journal of Neuroradiology, vol. 20, no. 1, pp. 63–73, 1999.
J. Biernaskie, D. Corbett, J. Peeling, J. Wells, and H. Lei, “A serial MR study of cerebral blood flow changes and lesion development following endothelin-1-induced ischemia in rats,” Magnetic Resonance in Medicine, vol. 46, no. 4, pp. 827–830, 2001.
M. Modo, R. P. Stroemer, E. Tang, T. Veizovic, P. Sowniski, and H. Hodges, “Neurological sequelae and long-term behavioural assessment of rats with transient middle cerebral artery occlusion,” Journal of Neuroscience Methods, vol. 104, no. 1, pp. 99–109, 2000.
C. P. Montoya, L. J. Campbell-Hope, K. D. Pemberton, and S. B. Dunnett, “The “staircase test”: a measure of independent forelimb reaching and grasping abilities in rats,” Journal of Neuroscience Methods, vol. 36, no. 2-3, pp. 219–228, 1991.
T. Schallert, S. M. Fleming, J. L. Leasure, J. L. Tillerson, and S. T. Bland, “CNS plasticity and assessment of forelimb sensorimotor outcome in unilateral rat models of stroke, cortical ablation, parkinsonism and spinal cord injury,” Neuropharmacology, vol. 39, no. 5, pp. 777–787, 2000.
T. Schallert, J. L. Leasure, and B. Kolb, “Experience-associated structural events, subependymal cellular proliferative activity, and functional recovery after injury to the central nervous system,” Journal of Cerebral Blood Flow and Metabolism, vol. 20, no. 11, pp. 1513–1528, 2000.
V. Windle, A. Szymanska, S. Granter-Button et al., “An analysis of four different methods of producing focal cerebral ischemia with endothelin-1 in the rat,” Experimental Neurology, vol. 201, no. 2, pp. 324–334, 2006.
M. D. Lindner, V. K. Gribkoff, N. A. Donlan, and T. A. Jones, “Long-lasting functional disabilities in middle-aged rats with small cerebral infarcts,” The Journal of Neuroscience, vol. 23, no. 34, pp. 10913–10922, 2003.
T. M. Barth and B. B. Stanfield, “The recovery of forelimb-placing behavior in rats with neonatal unilateral cortical damage involves the remaining hemisphere,” Journal of Neuroscience, vol. 10, no. 10, pp. 3449–3459, 1990.
T. Schallert, D. A. Kozlowski, J. L. Humm, and R. R. Cocke, “Use-dependent structural events in recovery of function,” Advances in Neurology, vol. 73, pp. 229–238, 1997.
T. Schallert and I. Q. Whishaw, “Bilateral cutaneous stimulation of the somatosensory system in hemidecorticate rats,” Behavioral Neuroscience, vol. 98, no. 3, pp. 518–540, 1984.
J. B. Bederson, L. H. Pitts, M. Tsuji, M. C. Nishimura, R. L. Davis, and H. Bartkowski, “Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination,” Stroke, vol. 17, no. 3, pp. 472–476, 1986.
J. B. Bederson, L. H. Pitts, S. M. Germano, M. C. Nishimura, R. L. Davis, and H. M. Bartkowski, “Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats,” Stroke, vol. 17, no. 6, pp. 1304–1308, 1986.
D. Xue, Z.-G. Huang, K. E. Smith, and A. M. Buchan, “Immediate or delayed mild hypothermia prevents focal cerebral infection,” Brain Research, vol. 587, no. 1, pp. 66–72, 1992.
