(Stroke. 1995;26:636-643.)
© 1995 American Heart Association, Inc.
Articles |
Neuronal Necrosis After Middle Cerebral Artery Occlusion in Wistar Rats Progresses at Different Time Intervals in the Caudoputamen and the Cortex
Presented at the 19th International Joint Conference on Stroke and Cerebral Circulation, San Diego, Calif, February 17-19, 1994, and published in abstract form in Stroke 1994;25:260.
From the Department of Pathology (Neuropathology), Henry Ford Hospital, Detroit, Mich (J.H.G., K.-F.L.), and Case Western Reserve University, Cleveland, Ohio (J.H.G., K.-L.H.).
Correspondence to Dr Julio H. Garcia, Department of Pathology (Neuropathology), Henry Ford Hospital, K-6, 2799 W Grand Blvd, Detroit, MI 48202-2689.
Background and Purpose Most brain lesions that develop after an artery is occluded evolve from an initial stage of "ischemic injury" (probably reversible) to an infarct or an area where most neurons become necrotic. There is scant information on the time that must elapse after the arterial occlusion for neurons to undergo irreversible injury. The objective of these experiments was to chart the time course and the topographic distribution of the neuronal necrosis that follows the occlusion of a large cerebral artery.
Methods One hundred fifty-one adult rats (including 15 controls) were used in this study. One hundred forty-seven had the right middle cerebral artery occluded for variable periods ranging from 30 minutes to 7 days. After processing the brains for histology, a meticulous structural evaluation of each specimen, including quantitation of necrotic neurons, was followed by a detailed statistical analysis of the neuronal counts.
Results Few neurons in isolated sites showed morphological signs of necrosis during the initial 4 hours; the first significant increase in the percentage of necrotic neurons (15%) was observed within the territory of the occluded artery after 6 hours (P<.05); 12 hours after the arterial occlusion most neurons (65%) had become necrotic (P<.0001). Pannecrosis involving neurons, glial cells, and blood vessels was observed at 72 to 96 hours. However, even at this time pannecrosis involved only the preoptic area and the lateral putamen; a few intact neurons remained visible in the cortex, and scattered necrotic neurons could be identified beyond the edges of the "area of pallor," which does not become clearly demarcated until 4 to 5 days after the arterial occlusion.
Conclusions There is a predictable progression in the development of neuronal necrosis after a permanent arterial occlusion. Irreversible changes appear first in the caudoputamen and then spread to the cortex. The causes for the progression of the lesion are not known; however, therapeutic interventions that start within the first 1 to 2 hours after the arterial occlusion may alter the histopathologic responses to this form of injury. It remains to be determined whether the extent of the neurological deficit induced by an arterial occlusion correlates with the number of necrotic neurons.
Key Words: cerebral ischemia • coagulation • neuronal death • occlusion
This article has been cited by other articles:
 |
|
 |
|
  A. Melani, S. Cipriani, M. G. Vannucchi, D. Nosi, C. Donati, P. Bruni, M. G. Giovannini, and F. Pedata Selective adenosine A2a receptor antagonism reduces JNK activation in oligodendrocytes after cerebral ischaemia Brain, June 1, 2009; 132(6): 1480 - 1495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. A. Oliveira and J. Goncalves In Situ Mitochondrial Ca2+ Buffering Differences of Intact Neurons and Astrocytes from Cortex and Striatum J. Biol. Chem., February 20, 2009; 284(8): 5010 - 5020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hasegawa, M. Morioka, S. Hasegawa, J. Matsumoto, T. Kawano, Y. Kai, S. Yano, K. Fukunaga, and J.-i. Kuratsu Therapeutic Time Window and Dose Dependence of Neuroprotective Effects of Sodium Orthovanadate following Transient Middle Cerebral Artery Occlusion in Rats J. Pharmacol. Exp. Ther., May 1, 2006; 317(2): 875 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Homi, H. Yang, R. D. Pearlstein, and H. P. Grocott Hemodilution During Cardiopulmonary Bypass Increases Cerebral Infarct Volume After Middle Cerebral Artery Occlusion in Rats Anesth. Analg., October 1, 2004; 99(4): 974 - 981. [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]
|
|
|
|
 |
|
 K. Saita, M. Chen, N. J. Spratt, M. J. Porritt, G. T. Liberatore, S. J. Read, C. R. Levi, G. A. Donnan, U. Ackermann, H. J. Tochon-Danguy, et al. Imaging the Ischemic Penumbra with 18F-Fluoromisonidazole in a Rat Model of Ischemic Stroke Stroke, April 1, 2004; 35(4): 975 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Kuge, K. Hikosaka, K.-i. Seki, K. Ohkura, K.-i. Nishijima, T. Kaji, S. Ueno, E. Tsukamoto, and N. Tamaki Characteristic Brain Distribution of 1-14C-Octanoate in a Rat Model of Focal Cerebral Ischemia in Comparison with Those of 123I-IMP and 123I-Iomazenil J. Nucl. Med., July 1, 2003; 44(7): 1168 - 1175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Gladstone, S. E. Black, and A. M. Hakim Toward Wisdom From Failure: Lessons From Neuroprotective Stroke Trials and New Therapeutic Directions Stroke, August 1, 2002; 33(8): 2123 - 2136. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Solenski, C. G. diPierro, P. A. Trimmer, A.-L. Kwan, and G. A. Helms Ultrastructural Changes of Neuronal Mitochondria After Transient and Permanent Cerebral Ischemia Stroke, March 1, 2002; 33(3): 816 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Li, K.-F. Liu, M. D. Silva, X. Meng, T. Gerriets, K. G. Helmer, J. D. Fenstermacher, C. H. Sotak, and M. Fisher Acute Postischemic Renormalization of the Apparent Diffusion Coefficient of Water is not Associated with Reversal of Astrocytic Swelling and Neuronal Shrinkage in Rats AJNR Am. J. Neuroradiol., February 1, 2002; 23(2): 180 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Takamatsu, H. Tsukada, A. Noda, T. Kakiuchi, S. Nishiyama, S. Nishimura, and K. Umemura FK506 Attenuates Early Ischemic Neuronal Death in a Monkey Model of Stroke J. Nucl. Med., December 1, 2001; 42(12): 1833 - 1840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Benchoua, C. Guegan, C. Couriaud, H. Hosseini, N. Sampaio, D. Morin, and B. Onteniente Specific Caspase Pathways Are Activated in the Two Stages of Cerebral Infarction J. Neurosci., September 15, 2001; 21(18): 7127 - 7134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ishikawa, K. Yokoyama, T. Kuroiwa, and K. Makita Evolution of cerebral ischaemia induced by thromboembolism in rats detected by early sequential MR imaging Br. J. Anaesth., September 1, 2001; 87(3): 469 - 476. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-F. Liu, F. Li, T. Tatlisumak, J. H. Garcia, C. H. Sotak, M. Fisher, and J. D. Fenstermacher Regional Variations in the Apparent Diffusion Coefficient and the Intracellular Distribution of Water in Rat Brain During Acute Focal Ischemia Stroke, August 1, 2001; 32(8): 1897 - 1905. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. von Kummer, H. Bourquain, S. Bastianello, L. Bozzao, C. Manelfe, D. Meier, and W. Hacke Early Prediction of Irreversible Brain Damage after Ischemic Stroke at CT Radiology, April 1, 2001; 219(1): 95 - 100. [Abstract] [Full Text]
|
|
|
|
|
|
W. Nakajima, A. Ishida, M. S. Lange, K. L. Gabrielson, M. A. Wilson, L. J. Martin, M. E. Blue, and M. V. Johnston Apoptosis Has a Prolonged Role in the Neurodegeneration after Hypoxic Ischemia in the Newborn Rat J. Neurosci., November 1, 2000; 20(21): 7994 - 8004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Matsushita, Y. Wu, J. Qiu, L. Lang-Lazdunski, L. Hirt, C. Waeber, B. T. Hyman, J. Yuan, and M. A. Moskowitz Fas Receptor and Neuronal Cell Death after Spinal Cord Ischemia J. Neurosci., September 15, 2000; 20(18): 6879 - 6887. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
F. Li, K.-F. Liu, M. D. Silva, T. Omae, C. H. Sotak, J. D. Fenstermacher, M. Fisher, C. Y. Hsu, and W. Lin Transient and Permanent Resolution of Ischemic Lesions on Diffusion-Weighted Imaging After Brief Periods of Focal Ischemia in Rats : Correlation With Histopathology Editorial Comment: Correlation With Histopathology Stroke, April 1, 2000; 31(4): 946 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, F. Colbourne, P. Sun, Z. Zhao, A. M. Buchan, and C. Iadecola Caspase Inhibitors Reduce Neuronal Injury After Focal but Not Global Cerebral Ischemia in Rats Editorial Comment Stroke, January 1, 2000; 31(1): 176 - 182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. G. Zhang, M. Chopp, A. Goussev, D. Lu, D. Morris, W. Tsang, C. Powers, and K.-L. Ho Cerebral Microvascular Obstruction by Fibrin is Associated with Upregulation of PAI-1 Acutely after Onset of Focal Embolic Ischemia in Rats J. Neurosci., December 15, 1999; 19(24): 10898 - 10907. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Melani, L. Pantoni, C. Corsi, L. Bianchi, A. Monopoli, R. Bertorelli, G. Pepeu, F. Pedata, and D. K. J. E. von Lubitz Striatal Outflow of Adenosine, Excitatory Amino Acids, {gamma}-Aminobutyric Acid, and Taurine in Awake Freely Moving Rats After Middle Cerebral Artery Occlusion : Correlations With Neurological Deficit and Histopathological Damage Editorial Comment: Correlations With Neurological Deficit and Histopathological Damage Stroke, November 1, 1999; 30(11): 2448 - 2455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Lipton Ischemic Cell Death in Brain Neurons Physiol Rev, October 1, 1999; 79(4): 1431 - 1568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Davis and D. Barer Neuroprotection in acute ischaemic stroke. II: Clinical potential Vascular Medicine, August 1, 1999; 4(3): 149 - 163. [Abstract] [PDF]
|
|
|
|
|
|
F. Colbourne, G. R. Sutherland, and R. N. Auer Electron Microscopic Evidence against Apoptosis as the Mechanism of Neuronal Death in Global Ischemia J. Neurosci., June 1, 1999; 19(11): 4200 - 4210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Boutin, F. Dauphin, E. T. MacKenzie, P. Jauzac, and R. C. Koehler Differential Time-Course Decreases in Nonselective, ΅-, {delta}-, and {kappa}-Opioid Receptors After Focal Cerebral Ischemia in Mice Editorial Comment Stroke, June 1, 1999; 30(6): 1271 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Iadecola, C. A. Salkowski, F. Zhang, T. Aber, M. Nagayama, S. N. Vogel, and M. Elizabeth Ross The Transcription Factor Interferon Regulatory Factor 1 Is Expressed after Cerebral Ischemia and Contributes to Ischemic Brain Injury J. Exp. Med., February 15, 1999; 189(4): 719 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shimizu-Sasamata, T. Kano, J. Rogowska, G. L. Wolf, M. A. Moskowitz, E. H. Lo, and C. Iadecola YM872, a Highly Water-Soluble AMPA Receptor Antagonist, Preserves the Hemodynamic Penumbra and Reduces Brain Injury After Permanent Focal Ischemia in Rats Editorial Comment Stroke, October 1, 1998; 29(10): 2141 - 2148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schmid-Elsaesser, S. Zausinger, E. Hungerhuber, A. Baethmann, H.-J. Reulen, and J. H. Garcia A Critical Reevaluation of the Intraluminal Thread Model of Focal Cerebral Ischemia : Evidence of Inadvertent Premature Reperfusion and Subarachnoid Hemorrhage in Rats by Laser-Doppler Flowmetry Editorial Comment: Evidence of Inadvertent Premature Reperfusion and Subarachnoid Hemorrhage in Rats by Laser-Doppler Flowmetry Stroke, October 1, 1998; 29(10): 2162 - 2170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Bolay, T. Dalkara, and J. H. Garcia Mechanisms of Motor Dysfunction After Transient MCA Occlusion: Persistent Transmission Failure in Cortical Synapses Is a Major Determinant Editorial Comment Stroke, September 1, 1998; 29(9): 1988 - 1994. [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]
|
|
|
|
 |
|
 L. Pantoni, C. Sarti, and D. Inzitari Cytokines and Cell Adhesion Molecules in Cerebral Ischemia : Experimental Bases and Therapeutic Perspectives Arterioscler. Thromb. Vasc. Biol., April 1, 1998; 18(4): 503 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Pantoni, L. Bartolini, G. Pracucci, D. Inzitari, and J. H. Garcia Interrater Agreement on a Simple Neurological Score in Rats Response Stroke, April 1, 1998; 29(4): 871 - 872. [Full Text] [PDF]
|
|
|
|
|
|
W.-D. Heiss, M. Grond, A. Thiel, M. Ghaemi, J. Sobesky, J. Rudolf, B. Bauer, and K. Wienhard Permanent Cortical Damage Detected by Flumazenil Positron Emission Tomography in Acute Stroke Stroke, February 1, 1998; 29(2): 454 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. G. Markgraf, N. L. Velayo, M. P. Johnson, D. R. McCarty, S. Medhi, J. R. Koehl, P. A. Chmielewski, M. D. Linnik, and J. A. Clemens Six-Hour Window of Opportunity for Calpain Inhibition in Focal Cerebral Ischemia in Rats Editorial Comment Stroke, January 1, 1998; 29(1): 152 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Iadecola, F. Zhang, R. Casey, M. Nagayama, and M. E. Ross Delayed Reduction of Ischemic Brain Injury and Neurological Deficits in Mice Lacking the Inducible Nitric Oxide Synthase Gene J. Neurosci., December 1, 1997; 17(23): 9157 - 9164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Garcia, K.-F. Liu, Z.-R. Ye, and J. A. Gutierrez Incomplete Infarct and Delayed Neuronal Death After Transient Middle Cerebral Artery Occlusion in Rats Stroke, November 1, 1997; 28(11): 2303 - 2310. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. Kato, G. K. Kanellopoulos, S. Matsuo, Y. J. Wu, M. F. Jacquin, C. Y. Hsu, D. W. Choi, and N. T. Kouchoukos PROTECTION OF RAT SPINAL CORD FROM ISCHEMIA WITH DEXTRORPHAN AND CYCLOHEXIMIDE: EFFECTS ON NECROSIS AND APOPTOSIS J. Thorac. Cardiovasc. Surg., October 1, 1997; 114(4): 609 - 618. [Abstract] [Full Text]
|
|
|
|
|
|
C. G. a. C. Oberlander The Kappa Opioid Agonist Niravoline Decreases Brain Edema in the Mouse Middle Cerebral Artery Occlusion Model of Stroke J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 1 - 6. [Abstract] [Full Text]
|
|
|
|
|
|
J. Nakagawara, B. Sperling, and N. A. Lassen Incomplete Brain Infarction of Reperfused Cortex May Be Quantitated With Iomazenil Stroke, January 1, 1997; 28(1): 124 - 132. [Abstract] [Full Text]
|
|
|
|
|
|
G. Gido, T. Kristian, B. K. Siesjo, and R. C. Koehler Extracellular Potassium in a Neocortical Core Area After Transient Focal Ischemia Stroke, January 1, 1997; 28(1): 206 - 210. [Abstract] [Full Text]
|
|
|
|
|
|
L. Pantoni, J. H. Garcia, J. A. Gutierrez, and W. I. Rosenblum Cerebral White Matter Is Highly Vulnerable to Ischemia Stroke, September 1, 1996; 27(9): 1641 - 1647. [Abstract] [Full Text]
|
|
|
|
|
|
J. H. Garcia, N. A. Lassen, C. Weiller, B. Sperling, and J. Nakagawara Ischemic Stroke and Incomplete Infarction Stroke, April 1, 1996; 27(4): 761 - 765. [Abstract] [Full Text]
|
|