Stroke, Vol 17, 472-476, Copyright © 1986 by American Heart Association
JB Bederson, LH Pitts, M Tsuji, MC Nishimura, RL Davis and H Bartkowski
We have examined the incidence and size of infarction after occlusion of
different portions of the rat middle cerebral artery (MCA) in order to
define the reliability and predictability of this model of brain ischemia.
We developed a neurologic examination and have correlated changes in
neurologic status with the size and location of areas of infarction. The
MCA was surgically occluded at different sites in six groups of normal
rats. After 24 hr, rats were evaluated for the extent of neurologic
deficits and graded as having severe, moderate, or no deficit using a new
examination developed for this model. After rats were sacrificed the
incidence of infarction was determined at histologic examination. In a
subset of rats, the size of the area of infarction was measured as a
percent of the area of a standard coronal section. Focal (1-2 mm) occlusion
of the MCA at its origin, at the olfactory tract, or lateral to the
inferior cerebral vein produced infarction in 13%, 67%, and 0% of rats,
respectively (N = 38) and produced variable neurologic deficits. However,
more extensive (3 or 6 mm) occlusion of the MCA beginning proximal to the
olfactory tract-- thus isolating lenticulostriate end-arteries from the
proximal and distal supply--produced infarctions of uniform size, location,
and with severe neurologic deficit (Grade 2) in 100% of rats (N = 17).
Neurologic deficit correlated significantly with the size of the infarcted
area (Grade 2, N = 17, 28 +/- 5% infarction; Grade 1, N = 5, 19 +/- 5%;
Grade 0, N = 3, 10 +/- 2%; p less than 0.05). We have characterized precise
anatomical sites of the MCA that when surgically occluded reliably produce
uniform cerebral infarction in rats, and have developed a neurologic
grading system that can be used to evaluate the effects of cerebral
ischemia rapidly and accurately. The model will be useful for experimental
assessment of new therapies for irreversible cerebral ischemia.
ARTICLES
Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination
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L. Belayev, I. Saul, K. Curbelo, R. Busto, A. Belayev, Y. Zhang, P. Riyamongkol, W. Zhao, and M. D. Ginsberg Experimental Intracerebral Hemorrhage in the Mouse: Histological, Behavioral, and Hemodynamic Characterization of a Double-Injection Model Stroke, September 1, 2003; 34(9): 2221 - 2227. [Abstract] [Full Text] [PDF]
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K. Becker, D. Kindrick, R. McCarron, J. Hallenbeck, and R. Winn Adoptive Transfer of Myelin Basic Protein-Tolerized Splenocytes to Naive Animals Reduces Infarct Size: A Role for Lymphocytes in Ischemic Brain Injury? Stroke, July 1, 2003; 34(7): 1809 - 1815. [Abstract] [Full Text] [PDF]
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J. Xu, J. Culman, A. Blume, S. Brecht, and P. Gohlke Chronic Treatment With a Low Dose of Lithium Protects the Brain Against Ischemic Injury by Reducing Apoptotic Death Stroke, May 1, 2003; 34(5): 1287 - 1292. [Abstract] [Full Text] [PDF]
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L. Belayev, L. Khoutorova, T. A. Deisher, A. Belayev, R. Busto, Y. Zhang, W. Zhao, and M. D. Ginsberg Neuroprotective Effect of SolCD39, a Novel Platelet Aggregation Inhibitor, on Transient Middle Cerebral Artery Occlusion in Rats Stroke, March 1, 2003; 34(3): 758 - 763. [Abstract] [Full Text] [PDF]
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R. M. Dijkhuizen, A. B. Singhal, J. B. Mandeville, O. Wu, E. F. Halpern, S. P. Finklestein, B. R. Rosen, and E. H. Lo Correlation between Brain Reorganization, Ischemic Damage, and Neurologic Status after Transient Focal Cerebral Ischemia in Rats: A Functional Magnetic Resonance Imaging Study J. Neurosci., January 15, 2003; 23(2): 510 - 517. [Abstract] [Full Text] [PDF]
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J. Chuquet, K. Benchenane, J. Toutain, E. T. MacKenzie, S. Roussel, and O. Touzani Selective Blockade of Endothelin-B Receptors Exacerbates Ischemic Brain Damage in the Rat Stroke, December 1, 2002; 33(12): 3019 - 3025. [Abstract] [Full Text] [PDF]
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A. Shuaib, C. Xu Wang, T. Yang, and R. Noor Effects of Nonpeptide V1 Vasopressin Receptor Antagonist SR-49059 on Infarction Volume and Recovery of Function in a Focal Embolic Stroke Model Stroke, December 1, 2002; 33(12): 3033 - 3037. [Abstract] [Full Text] [PDF]
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S. Parmentier-Batteur, K. Jin, X. O. Mao, L. Xie, and D. A. Greenberg Increased Severity of Stroke in CB1 Cannabinoid Receptor Knock-Out Mice J. Neurosci., November 15, 2002; 22(22): 9771 - 9775. [Abstract] [Full Text] [PDF]
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 M. Aarts, Y. Liu, L. Liu, S. Besshoh, M. Arundine, J. W. Gurd, Y.-T. Wang, M. W. Salter, and M. Tymianski Treatment of Ischemic Brain Damage by Perturbing NMDA Receptor- PSD-95 Protein Interactions Science, October 25, 2002; 298(5594): 846 - 850. [Abstract] [Full Text] [PDF]
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G. Trendelenburg, K. Prass, J. Priller, K. Kapinya, A. Polley, C. Muselmann, K. Ruscher, U. Kannbley, A. O. Schmitt, S. Castell, et al. Serial Analysis of Gene Expression Identifies Metallothionein-II as Major Neuroprotective Gene in Mouse Focal Cerebral Ischemia J. Neurosci., July 15, 2002; 22(14): 5879 - 5888. [Abstract] [Full Text] [PDF]
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F. Mauler, J. Mittendorf, E. Horvath, and J. de Vry Characterization of the Diarylether Sulfonylester (-)-(R)-3-(2-Hydroxymethylindanyl-4-oxy)phenyl-4,4,4-trifluoro-1-sulfonate (BAY 38-7271) as a Potent Cannabinoid Receptor Agonist with Neuroprotective Properties J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 359 - 368. [Abstract] [Full Text] [PDF]
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R. R. Leker, A. Teichner, N. Grigoriadis, H. Ovadia, D. E. Brenneman, M. Fridkin, E. Giladi, J. Romano, and I. Gozes NAP, a Femtomolar-Acting Peptide, Protects the Brain Against Ischemic Injury by Reducing Apoptotic Death Stroke, April 1, 2002; 33(4): 1085 - 1092. [Abstract] [Full Text] [PDF]
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 M. B. Abou-Donia, A. M. Dechkovskaia, L. B. Goldstein, S. L. Bullman, and W. A. Khan Sensorimotor Deficit and Cholinergic Changes following Coexposure with Pyridostigmine Bromide and Sarin in Rats Toxicol. Sci., March 1, 2002; 66(1): 148 - 158. [Abstract] [Full Text] [PDF]
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T. Sumii and E. H. Lo Involvement of Matrix Metalloproteinase in Thrombolysis-Associated Hemorrhagic Transformation After Embolic Focal Ischemia in Rats Stroke, March 1, 2002; 33(3): 831 - 836. [Abstract] [Full Text] [PDF]
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M. Campanella, C. Sciorati, G. Tarozzo, and M. Beltramo Flow Cytometric Analysis of Inflammatory Cells in Ischemic Rat Brain Stroke, February 1, 2002; 33(2): 586 - 592. [Abstract] [Full Text] [PDF]
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T. Engelhorn, R. von Kummer, W. Reith, M. Forsting, and A. Doerfler What Is Effective in Malignant Middle Cerebral Artery Infarction: Reperfusion, Craniectomy, or Both?: An Experimental Study in Rats Stroke, February 1, 2002; 33(2): 617 - 622. [Abstract] [Full Text] [PDF]
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R. L. Roof, G. P. Schielke, X. Ren, and E. D. Hall A Comparison of Long-Term Functional Outcome After 2 Middle Cerebral Artery Occlusion Models in Rats Stroke, November 1, 2001; 32(11): 2648 - 2657. [Abstract] [Full Text] [PDF]
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A. J. Williams, X. M. Lu, B. Slusher, and F. C. Tortella Electroencephalogram Analysis and Neuroprotective Profile of the N-Acetylated-alpha -Linked Acidic Dipeptidase Inhibitor, GPI5232, in Normal and Brain-Injured Rats J. Pharmacol. Exp. Ther., October 1, 2001; 299(1): 48 - 57. [Abstract] [Full Text] [PDF]
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A. C. DeVries, H.-D. Joh, O. Bernard, K. Hattori, P. D. Hurn, R. J. Traystman, and N. J. Alkayed Social stress exacerbates stroke outcome by suppressing Bcl-2 expression PNAS, September 5, 2001; (2001) 201215298. [Abstract] [Full Text] [PDF]
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D. Ito, K. Tanaka, S. Suzuki, T. Dembo, and Y. Fukuuchi Enhanced Expression of Iba1, Ionized Calcium-Binding Adapter Molecule 1, After Transient Focal Cerebral Ischemia In Rat Brain Stroke, May 1, 2001; 32(5): 1208 - 1215. [Abstract] [Full Text] [PDF]
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M. B. Abou-Donia, L. B. Goldstein, K. H. Jones, A. A. Abdel-Rahman, T. V. Damodaran, A. M. Dechkovskaia, S. L. Bullman, B. E. Amir, and W. A. Khan Locomotor and Sensorimotor Performance Deficit in Rats following Exposure to Pyridostigmine Bromide, DEET, and Permethrin, Alone and in Combination Toxicol. Sci., April 1, 2001; 60(2): 305 - 314. [Abstract] [Full Text] [PDF]
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K. W. Park, C. Metais, H. B. Dai, M. E. Comunale, and F. W. Sellke Microvascular Endothelial Dysfunction and its Mechanism in a Rat Model of Subarachnoid Hemorrhage Anesth. Analg., April 1, 2001; 92(4): 990 - 996. [Abstract] [Full Text] [PDF]
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K. Becker, D. Kindrick, J. Relton, J. Harlan, R. Winn, and M. A. Yenari Antibody to the {{alpha}}4 Integrin Decreases Infarct Size in Transient Focal Cerebral Ischemia in Rats Editorial Comment Stroke, January 1, 2001; 32(1): 206 - 211. [Abstract] [Full Text] [PDF]
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H. Yanamoto, I. Nagata, Y. Niitsu, Z. Zhang, J.-H. Xue, N. Sakai, H. Kikuchi, and C. Iadecola Prolonged Mild Hypothermia Therapy Protects the Brain Against Permanent Focal Ischemia Editorial Comment Stroke, January 1, 2001; 32(1): 232 - 239. [Abstract] [Full Text] [PDF]
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K. Fassbender, M. Fatar, A. Ragoschke, M. Picard, T. Bertsch, S. Kuehl, and M. Hennerici Subacute But Not Acute Generation of Nitric Oxide in Focal Cerebral Ischemia Stroke, September 1, 2000; 31(9): 2208 - 2211. [Abstract] [Full Text] [PDF]
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Y. Toshima, S.-i. Satoh, I. Ikegaki, T. Asano, and W. D. Dietrich A New Model of Cerebral Microthrombosis in Rats and the Neuroprotective Effect of a Rho-Kinase Inhibitor Editorial Comment Stroke, September 1, 2000; 31(9): 2245 - 2250. [Abstract] [Full Text] [PDF]
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K. Hattori, H. Lee, P. D. Hurn, B. J. Crain, R. J. Traystman, A. C. DeVries, and B. G. Lyeth Cognitive Deficits After Focal Cerebral Ischemia in Mice Editorial Comment Stroke, August 1, 2000; 31(8): 1939 - 1944. [Abstract] [Full Text] [PDF]
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A. J. Williams, J. R. Dave, J. B. Phillips, Y. Lin, R. T. McCabe, and F. C. Tortella Neuroprotective Efficacy and Therapeutic Window of the High-Affinity N-Methyl-D-aspartate Antagonist Conantokin-G: In Vitro (Primary Cerebellar Neurons) and In Vivo (Rat Model of Transient Focal Brain Ischemia) Studies J. Pharmacol. Exp. Ther., July 1, 2000; 294(1): 378 - 386. [Abstract] [Full Text]
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T. Mokudai, I. A. Ayoub, Y. Sakakibara, E-J. Lee, C. S. Ogilvy, K. I. Maynard, and K. Maiese Delayed Treatment With Nicotinamide (Vitamin B3) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats Editorial Comment Stroke, July 1, 2000; 31(7): 1679 - 1685. [Abstract] [Full Text] [PDF]
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D. Reglodi, A. Somogyvari-Vigh, S. Vigh, T. Kozicz, A. Arimura, and S. P. Finklestein Delayed Systemic Administration of PACAP38 Is Neuroprotective in Transient Middle Cerebral Artery Occlusion in the Rat Editorial Comment Stroke, June 1, 2000; 31(6): 1411 - 1417. [Abstract] [Full Text] [PDF]
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I. Harukuni, A. Bhardwaj, A. B. Shaivitz, A. C. DeVries, E. D. London, P. D. Hurn, R. J. Traystman, J. R. Kirsch, and F. M. Faraci {sigma}1-Receptor Ligand 4-Phenyl-1-(4-Phenylbutyl)-Piperidine Affords Neuroprotection From Focal Ischemia With Prolonged Reperfusion • Editorial Comment Stroke, April 1, 2000; 31(4): 976 - 982. [Abstract] [Full Text] [PDF]
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Z. He, T. Yamawaki, S. Yang, A. L. Day, J. W. Simpkins, H. Naritomi, and W. I. Rosenblum Experimental Model of Small Deep Infarcts Involving the Hypothalamus in Rats : Changes in Body Temperature and Postural Reflex • Editorial Comment: Changes in Body Temperature and Postural Reflex Stroke, December 1, 1999; 30(12): 2743 - 2751. [Abstract] [Full Text] [PDF]
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