(Stroke. 1997;28:632-638.)
© 1997 American Heart Association, Inc.
Articles |
Early Reperfusion in the Anesthetized Baboon Reduces Brain Damage Following Middle Cerebral Artery Occlusion
A Quantitative Analysis of Infarction Volume
From INSERM U 320, Cyceron (A.R.Y., G.S., J.-C.B.), Biomedical Cyclotron Unit of Caen (A.R.Y., O.T., J.-M.D., G.S., E.T.M., J.-C.B.), University of Caen-CNRS UMR 6551 (O.T., E.T.M.), France; and Dipartimento di Scienze Neurologiche I°Clinica Neurologica–Universita "La Sapienza," Rome, Italy.
Correspondence to Dr Alan R. Young, Jules Horowitz Campus INSERM U 320 Cyceron, Biomedical Cyclotron Unit of Caen, Blvd Henri Becquerel, BP 5229, 14074 Caen Cedex, France. E-mail young{at}cyceron.fr.
Background and Purpose Because in humans the clinical benefits of reperfusion remain controversial, it is important to determine whether reperfusion per se reduces infarct volume. In the nonhuman primate, mostly semiquantitative assessments of infarction have been performed. When ischemic volumes have been calculated, it has been for the acute or subacute stages of experimental stroke and may thus not adequately reflect the total volume of consolidated infarction.
Methods Anesthetized baboons were subjected to 6 hours of either reversible or permanent middle cerebral artery occlusion (MCAO). Approximately 4 weeks later, the brains were processed for neuropathological examination to allow assessment of the final infarct volume determined by the difference of healthy tissue between occluded and nonoccluded hemispheres.
Results Reversible MCAO resulted in a small essentially subcortical infarction (mean±SD, 0.58±0.31 cm3) in 6 of 10 baboons: the infarct (pannecrosis) was restricted to the head of the caudate nucleus, internal capsule, and putamen; 4 of 10 baboons showed no evidence of macroscopic infarction. Permanent MCAO produced a larger subcortical infarct in all 7 baboons studied (2.37±1.32 cm3; P=.0006 by Wilcoxon-Mann-Whitney test); the lesion was more extensive and encompassed the external capsule and, in 2 baboons, the adjacent insular cortex.
Conclusions We conclude that under optimal experimental conditions, an ischemic episode of 6 hours in duration is well tolerated in the anesthetized adolescent baboon, with 4 animals showing no signs of macroscopic brain damage. Thus, early reestablishment of cerebral blood flow after a focal ischemic insult is not detrimental but indeed is beneficial in terms of the final infarct volume (both at the subcortical and cortical levels) produced by occlusion of a major cerebral artery. The data further suggest a feasible time window in which to initiate and continue therapeutic interventions.
Key Words: cerebral ischemia • middle cerebral artery occlusion • reperfusion • stroke, experimental • baboons
This article has been cited by other articles:
 |
|
 |
|
  C. Rink, G. Christoforidis, A. Abduljalil, M. Kontzialis, V. Bergdall, S. Roy, S. Khanna, A. Slivka, M. Knopp, and C. K. Sen Minimally invasive neuroradiologic model of preclinical transient middle cerebral artery occlusion in canines PNAS, September 16, 2008; 105(37): 14100 - 14105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Giffard, B. Landeau, N. Kerrouche, A. R. Young, L. Barre, and J.-C. Baron Decreased Chronic-Stage Cortical 11C-Flumazenil Binding After Focal Ischemia-Reperfusion in Baboons: A Marker of Selective Neuronal Loss? Stroke, March 1, 2008; 39(3): 991 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. G. Phan, G. A. Donnan, P. M. Wright, and D. C. Reutens A Digital Map of Middle Cerebral Artery Infarcts Associated With Middle Cerebral Artery Trunk and Branch Occlusion Stroke, May 1, 2005; 36(5): 986 - 991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. J. del Zoppo TIAs and the pathology of cerebral ischemia Neurology, April 27, 2004; 62(8_suppl_6): S15 - S19. [Full Text]
|
|
|
|
 |
|
 H S Markus Cerebral perfusion and stroke J. Neurol. Neurosurg. Psychiatry, March 1, 2004; 75(3): 353 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Markus, D.C. Reutens, S. Kazui, S. Read, P. Wright, B.R. Chambers, J.I. Sachinidis, H.J. Tochon-Danguy, and G.A. Donnan Topography and Temporal Evolution of Hypoxic Viable Tissue Identified by 18F-Fluoromisonidazole Positron Emission Tomography in Humans After Ischemic Stroke Stroke, November 1, 2003; 34(11): 2646 - 2652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Labiche, F. Al-Senani, A. W. Wojner, J. C. Grotta, M. Malkoff, and A. V. Alexandrov Is the Benefit of Early Recanalization Sustained at 3 Months?: A Prospective Cohort Study Stroke, March 1, 2003; 34(3): 695 - 698. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Hamberg, G. J. Hunter, K. I. Maynard, C. Owen, P. P. Morris, C. M. Putman, C. Ogilvy, and R. G. Gonzalez Functional CT Perfusion Imaging in Predicting the Extent of Cerebral Infarction from a 3-Hour Middle Cerebral Arterial Occlusion in a Primate Stroke Model AJNR Am. J. Neuroradiol., June 1, 2002; 23(6): 1013 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Kidwell, J. L. Saver, J. Mattiello, S. Starkman, F. Vinuela, G. Duckwiler, Y.P. Gobin, R. Jahan, P. Vespa, J. P. Villablanca, et al. Diffusion-perfusion MRI characterization of post-recanalization hyperperfusion in humans Neurology, December 11, 2001; 57(11): 2015 - 2021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Molina, J. Montaner, S. Abilleira, J. F. Arenillas, M. Ribo, R. Huertas, F. Romero, and J. Alvarez-Sabin Time Course of Tissue Plasminogen Activator-Induced Recanalization in Acute Cardioembolic Stroke: A Case-Control Study Stroke, December 1, 2001; 32(12): 2821 - 2827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Christou, A. V. Alexandrov, W. S. Burgin, A. W. Wojner, R. A. Felberg, M. Malkoff, and J. C. Grotta Timing of Recanalization After Tissue Plasminogen Activator Therapy Determined by Transcranial Doppler Correlates With Clinical Recovery From Ischemic Stroke Stroke, August 1, 2000; 31(8): 1812 - 1816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Marchal, K. Benali, S. Iglesias, F. Viader, J.-M. Derlon, and J.-C. Baron Voxel-based mapping of irreversible ischaemic damage with PET in acute stroke Brain, December 1, 1999; 122(12): 2387 - 2400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Recommendations for Standards Regarding Preclinical Neuroprotective and Restorative Drug Development Stroke, December 1, 1999; 30(12): 2752 - 2758. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Pantano, F. Caramia, L. Bozzao, C. Dieler, and R. von Kummer Delayed Increase in Infarct Volume After Cerebral Ischemia : Correlations with Thrombolytic Treatment and Clinical Outcome Stroke, March 1, 1999; 30(3): 502 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-I. Kawano, Y. Ikeda, K. Kondo, and K. Umemura Increased cerebral infarction by cyclic flow reductions: studies in the guinea pig MCA thrombosis model Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1998; 275(5): R1578 - R1583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Frazee, X. Luo, G. Luan, D. S. Hinton, D. A. Hovda, M. S. Shiroishi, L. T. Barcliff, and H. A. Kontos Retrograde Transvenous Neuroperfusion: A Back Door Treatment for Stroke • Editorial Comment Stroke, September 1, 1998; 29(9): 1912 - 1916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J DEL ZOPPO, R. VON KUMMER, and G. F HAMANN Ischaemic damage of brain microvessels: inherent risks for thrombolytic treatment in stroke J. Neurol. Neurosurg. Psychiatry, July 1, 1998; 65(1): 1 - 9. [Full Text]
|
|
|
|
|
|
M. Tagaya, K.-F. Liu, B. Copeland, D. Seiffert, R. Engler, J. H. Garcia, and G. J. del Zoppo DNA Scission After Focal Brain Ischemia : Temporal Differences in Two Species Stroke, June 1, 1997; 28(6): 1245 - 1254. [Abstract] [Full Text]
|
|