Experimental Models of Human Stroke

  • Karen A. Seta
  • R. Christian Crumrine
  • Tim S. Whittingham
  • W. David Lust
  • David W. McCandless
Part of the Neuromethods book series (NM, volume 22)


Stroke in humans consists of a focal neurological deficit that develops abruptly, attributable to either cerebral vessel occlusion or to the spontaneous rupture of an intracranial artery with hemorrhage into the brain parenchyma or subarachnoid space (Walker and Marx, 1981). Brain infarction, a localized lesion caused by the occlusion of a brain vessel (usually an artery), accounts for about 75% of the lesions produced by stroke, with brain hemorrhage (11%) and subarachnoid hemorrhage (5%) accounting for most of the rest (Anderson and Whisnant, 1982; Robins and Baum, 1981; Sacco et al., 1982). Thus, human stroke takes many forms depending on the etiology and spatial/temporal characteristics of the lesion. Consequently, there has been a variety of experimental stroke models developed to mimic the conditions that arise in human cerebrovascular accidents. These include many varied paradigms: in vivo and in vitro, global and focal, complete and incomplete ischemia, as well as hemorrhagic and nonhemorrhagic insults. In addition, these models may be adapted to study the events that occur upon recirculation following an ischemic episode. Two of these models will be described in detail: the bilateral common carotid artery occlusion model of global ischemia in the gerbil, and the middle cerebral artery occlusion model of focal ischemia in the rat.


Middle Cerebral Artery Common Carotid Artery Global Ischemia Focal Ischemia Bilateral Common Carotid Artery Occlusion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Adelman S. M. (1981) Economic impact. Stroke 12, I-69–I-78.Google Scholar
  2. Ahmed Z., Walker P. S., and Fellows R. E. (1983) Properties of neurons from dissociated fetal rat brain in serum-free culture. J. Neurosci. 3, 2448–2462.PubMedGoogle Scholar
  3. Anderson G. L. and Whisnant J. P. (1982) A comparison of trends in mortality from stroke in the United States and Rochester, Minnesota Stroke 13, 804–809.PubMedGoogle Scholar
  4. Astrup J., Symon L., Branstron N. M., and Lassen N. A. (1977) Cortical evoked potential and extracellular K+ and H+ at critical levels of brain ischemia. Stroke 8, 51–57.PubMedGoogle Scholar
  5. Atkinson D. E. (1968) The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback monitors. Biochemistry 7, 4030–4034.PubMedGoogle Scholar
  6. Aveldano M. I. and Bazan N. G. (1975) Differential lipid deacyclation during brain ischemia in a homotherm and poikilotherm. Content and composition of free fatty acids and triacylglycerols. Brain Res. l00, 99–110.Google Scholar
  7. Bak I. J., Misgeld U., Weiler M., and Morgan E. (1980) The preservation of nerve cells in rat neostriatal slices maintained in vitro: A morphological study. Brain Res. 197, 341–353.PubMedGoogle Scholar
  8. Benveniste H., Jorgensen M. B., Sandberg M., Christensen T., Hagberg H., and Diemer N. H. (1989) Ischemic damage and hippocampal CA1 is dependent on glutamate release and intact innervation from CA3. J. Cereb. Blood Flow Metab. 9, 629–639.PubMedGoogle Scholar
  9. Berry K., Wisniewski H. M., Svarzbein L., and Baez S. (1975) On the relationship of brain vasculature to production of neurological deficit and morphological changes following acute unilateral common carotid artery ligation in gerbils. J. Neurol Sci. 28, 75–92.Google Scholar
  10. Bertman L., Dahlgren N., and Siesjo B. K. (1979) Cerebral oxygen consumption and blood flow in hypoxia: Influence of sympathoadrenal activation. Stroke 10, 20–30.Google Scholar
  11. Bird M. M. (1983) Neurons and glial cells in long term cultures of previously dissociated newborn mouse cerebral cortex. J. Anat. 136, 293–305.PubMedGoogle Scholar
  12. Blomqvist P., Mabe H., Ingvar M., and Siesjo B. K. (1984) Models for studying long-term recovery following forebrain ischemia in the rat. 1. Circulatory and functional effects of 4-vessel occlusion. Acta Neurol. Scand. 69, 376–384.PubMedGoogle Scholar
  13. Booher J. and Sensenbrenner M. (1972) Growth and cultivation of dissociated neurons and glial cells from embryonic chick, rat and human brain in flask cultures. Neurobiology 2, 97–105.PubMedGoogle Scholar
  14. Bomstein M. B. and Model P. G. (1972) Development of synapses and my-elin in cultures of dissociated embryonic mouse spinal cord, medulla and cerebrum. Brain Res. 37, 287–293.Google Scholar
  15. Bralet J., Beley P., Bralet A.-M., and Beley A. (1983) Comparison of the effects of hypertonic glycerol and urea on brain edema, energy metabolism and blood flow following cerebral microembolism in the rat. Deleterious effect of glycerol treatment. Stroke 14, 597–604.PubMedGoogle Scholar
  16. Brewer G. J. and Cotman C. W. (1989) Survival and growth of hippocampal neurons in defined medium at low density: Advantages of a sandwich culture technique or low oxygen. Brain Res. 494, 65–74.PubMedGoogle Scholar
  17. Brint S., Jacewicz M., Kiessling M., Tanabe J., and 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, 474–485PubMedGoogle Scholar
  18. Brown A. W. and Brierley J. B. (1968) The nature, distribution and earliest stages of anoxic-ischemic nerve cell damage in the rat brain as defined by the optical microscope. Br. J. Exp. Pathol. 49, 87–106.PubMedGoogle Scholar
  19. Busto R. and Ginsberg M. D. (1985) Graded focal cerebral ischemia in the rat by unilateral carotid artery occlusion and elevated intracranial pressure: Hemodynamic and biochemical characterization. Stroke 16, 466–476.PubMedGoogle Scholar
  20. Busto R., Dietrich W. D., Globus M. Y.-T., Valdes I., Scheinberg P., and Ginsberg M. (1987) Small differences in intraischemic brain temperature critically determine the extent of ischemic neuronal injury. J. Cereb. Blood Flow Metab. 7, 729–738.PubMedGoogle Scholar
  21. Busto R., Dietrich W. D., Globus M. Y.-T., and Ginsberg M. D. (1989) The importance of brain temperature in cerebral ischemic injury. Stroke 20, 1113–1114.PubMedGoogle Scholar
  22. Cavanaugh M. W. (1955) Neuron development from trypsin-dissociated cells of differentiated spinal cord of the chick embryo. Exp. Cell Res 9, 42–48.PubMedGoogle Scholar
  23. Cervos-Navarro J. and Ferszt R. (1980) Brain edema: Pathology, diagnosis and therapy, in Advances in Natrology, vol. 28, Raven Press, New York.Google Scholar
  24. Choi D. W. (1987) Ionic dependence of glutamate neurotoxicity. J. Neurosci. 7, 369–379.PubMedGoogle Scholar
  25. Cohn R. (1979) Convulsive activity in gerbils subjected to cerebral ischemia. Exp. Neurol. 65, 391–397.PubMedGoogle Scholar
  26. Cox B. and Lomax P. (1976) Brain amines and spontaneous epileptic seizures in the Mongolian gerbil. Pharmacol. Biochem. Behav. 4, 263–267.PubMedGoogle Scholar
  27. Coyle P. and Jokelainen P. T. (1983) Differential outcome to middle cerebral artery occlusion in spontaneously hypertensive stroke-prone (SHRSP) and Wistar Kyoto (WKY) rats. Stroke 14, 605–611.PubMedGoogle Scholar
  28. Coyle P., Odenheimer D. J., and Sing C. F. (1984) Cerebral infarction after middle cerebral artery occlusion in progenies of spontaneously stroke-prone and normal rats. Stroke 15, 711–716.PubMedGoogle Scholar
  29. Coyle P. (1986) Different susceptibilities to cerebral infarction in spontaneously hypertensive (SHR) and normotensive SpragueDawley rats. Stroke 17, 520–525.PubMedGoogle Scholar
  30. Cusimano M. D. and Ameli F. M. (1989) Transient cerebral ischemia. Can. Med. Assoc. J. 140, 27–33.Google Scholar
  31. Dietrich W. D., Busto R., Watson B. D., Scheinberg P., and Ginsberg M. D. (1987) Photochemically induced cerebral infarction. II. Edema and blood-brain barrier disruption. Acta Neuropathol. Gkrl) 72, 326–334.Google Scholar
  32. Duverger D. and MacKenzie E. T. (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.PubMedGoogle Scholar
  33. Ebel A., Massarelli R., Sensenbrenner M., and Mandel P. (1974) Choline acetyltransferase and acetylcholinesterase activities in chicken brain hemispheres in vivo and in cell culture. Brain Res. 76, 461–472.PubMedGoogle Scholar
  34. Elliott K. A. C. (1955) Tissue slice technique, in Methods in Enzymology, vol. 1 (Colowick, S. P. and Kaplan, N. O, eds.), Academic, New York, pp. 3–19.Google Scholar
  35. Faiman M. D., Myers M. B., and Schowen R. L. (1973) Post-mortem degradation kinetics of brain norepinephrine. Biochem. Pharmacol. 22, 2171–2181.PubMedGoogle Scholar
  36. Flamm E. S., Demopoulos H. B., Seligman M. L., Poser R. G., and Ransohoff J. (1978) Free radicals in cerebral ischemia. Stroke 9, 445–447.PubMedGoogle Scholar
  37. Folbergrova J., Ponten U., and Siesjo B. K. (1974) Patterns of change in brain carbohydrate metabolites, amino acids and organic phosphates at increased carbon dioxide tensions. J. Neurochem. 22, 1115–1125.PubMedGoogle Scholar
  38. Frotscher M., Misgeld U., and Nitsch C. (1981) Ultrastructure of mossy fiber endings in in vitro hippocampal slices. Exp. Brain Res. 41, 247–255.PubMedGoogle Scholar
  39. Fujii T., Baumgartl H., and Lubbers D. W. (1982) Limiting section thickness of guinea pig olfactory cortical slices studied from tissue PO2 values and electrical activities. Pfluger Arch. 393, 83–87.Google Scholar
  40. Furlow T. W. (1982) Cerebral ischemia produced by four-vessel occlusion in the rat: A quantitative evaluation of cerebral blood flow. Stroke 13, 852–855.PubMedGoogle Scholar
  41. Futrell N., Watson B. D., Dietrich W. D., Prado R., Millikan C., and Ginsberg M. D. (1988) A new model of embolic stroke produced by photochemical injury to the carotid artery in the rat. Ann. Neurol. 23, 251–257.PubMedGoogle Scholar
  42. Gahwiler B. H. and Brown D. A. (1985) Functional innervation of cultured hippocampal neurones by cholinergic afferents from co-cultured septal explants. Nature 313, 577–579.PubMedGoogle Scholar
  43. Gahwiler B. H. and Brown D. A. (1987) Effects of dihydropyridines on calcium currents in CA3 pyramidal cells in slice cultures of rat hippocampus. Neurosience 20, 731–738.Google Scholar
  44. Gahwiler B. H. (1988) Organotypic cultures of neural tissue. Trends Neurosci., 11, 484–489.PubMedGoogle Scholar
  45. Garcia J. H. (1984) Experimental ischemic stroke: A review. Stroke 15, 5–14.PubMedGoogle Scholar
  46. Garthwaite J., Woodhams P. L., Collins M. J., and Balazs R. (1979) On the preparation of brain slices: Morphology and cyclic nucleotides. Brain Res. 173, 373–377.PubMedGoogle Scholar
  47. Gaudet R. J. and Levine L. (1979) Transient cerebral ischemia and brain pros-taglandins. Biochem. Biophys. Res. Commun. 86, 893–901.PubMedGoogle Scholar
  48. Gerbicke-Harter P. J., Althaus H. H., Rittner I., and Neuhoff V. (1984) Bulk separation and long term culture of oligodendrocytes from adult pig brain. I. Morphological studies. J. Neurochem. 42, 357–368.Google Scholar
  49. Giffard R. G., Monyer H., Christine C. W., and Choi D. W. (1990) Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxygen-glucose deprivation neuronal injury in cortical cultures. Brain Res. 506, 339–342.PubMedGoogle Scholar
  50. Ginsberg M. D. and Busto R. (1989) Rodent models of cerebral ischemia. Stroke 20, 1627–1642.PubMedGoogle Scholar
  51. Globus M. Y.-T., Busto R., Dietrich W. D., Martinez E., Valdes I., and Ginsberg M. D. (1988) Effect of ischemia on the in vivo release of striatal do-pamine, glutamate, and GABA studies by intracerebral dialysis. J. Neurochem. 51, 1455–1464.PubMedGoogle Scholar
  52. Goldberg M. P., Monyer H., Weiss J. H., and Choi D. W. (1988) Adenosine reduces cortical neuronal injury induced by oxygen or glucose deprivation in vitro. Neurosci. Lett. 89, 323–327.PubMedGoogle Scholar
  53. Gorelick P. B. (1989) Etiology and management of ischemic stroke. Comprehensive Therapy 15, 60–65.PubMedGoogle Scholar
  54. Grosse G. and Lindner G. (1970) Untersuchungen zur Differenzierung isolierter Nerven-und Gliazellen des zentralnervosen Gewebes von Huhnerembryonen in der Zellkultur. J. Hirnforsch 12, 207–215.PubMedGoogle Scholar
  55. Hallmayer D., Hossmann K.-A., and Mies G. (1985) Low dose of barbiturates for prevention of hippocampal lesions after brief ischemic episodes. Acta Neuropathol. (Berl) 68, 27–31.Google Scholar
  56. Hansen A. J. and Zeuthan T. (1981) Extracellular ion concentration during spreading depression and ischemia in the rat brain cortex. Acta Physiol. Scand. l13, 437–445.Google Scholar
  57. Hansen A. J., Hounsgaard J., and Jahnsen H. (1982) Anoxia increases potassium conductance in hippocampal nerve cells. Acta Physiol. Stand. 115, 301–310.Google Scholar
  58. Harrison R. G. (1907) Observations on the living developing nerve fiber. Soc. Exp. Biol. Med. Proc. 241, 140–150.Google Scholar
  59. Hawkins R. A., Williamson D. H., and Krebs H. A. (1971) Ketone body utilization by adult and suckling rat brain in vivo. Biochem. J. 122, 13–18.PubMedGoogle Scholar
  60. Hill N. D., Millikan C. H., Wakim K. C., and Sayre G. P. (1955) Studies in cerebrovascular disease. VII. Experimental production of cerebral infarction by intracarotid injection of homologous blood clot. Mayo Clin. Proc. 30, 625–633.Google Scholar
  61. Hillered L., Persson L., Ponten U., and Ungerstit U. (1989) Chemical changes in the extracellular fluid of human cerebral cortex during ischemia measured by intracerebral microdialysis. J. Neurochem. 52, S55B.Google Scholar
  62. Hogue M. J. (1947) Human fetal brain cells in tissue culture: Their identification and motility. J. Exp. Zool. 106, 85–103.PubMedGoogle Scholar
  63. Honegger P. and Richelson E. (1976) Biochemical differentiation of mechanically dissociated mammalian brain in aggregating cell culture. Brain Res. 109, 335–354.PubMedGoogle Scholar
  64. Hossmann K.-A. and Olsson Y. (1970) Suppression and recovery of neuro-nal function in transient cerebral ischemia. Brain Res. 22, 313–325.PubMedGoogle Scholar
  65. Hossmann K. A., Lechtape-Gruter H., and Hossmann V. (1973) The role of cerebral blood flow for the recovery of the brain after prolonged ischemia. Z. Neurol. 204, 281–299.PubMedGoogle Scholar
  66. Hossmann K. A. and Schuier F. J. (1980) Experimental brain infarct in cats: I. Pathophysiological observations. Stroke 11, 583–592.PubMedGoogle Scholar
  67. Hudgins W. R. and Garcia J. H. (1970) Transorbital approach to the middle cerebral artery of the squirrel monkey: A technique for experimental cerebral infarction applicable to ultrastructural studies. Stroke 1, 107–111.PubMedGoogle Scholar
  68. Ibayashi S., Fujishima M., Sadoshima S., Yoshida F., Shiokawa O., Ogata J., and Omae T. (1986) Cerebral blood flow and tissue metabolism in experimental cerebral ischemia of spontaneously hypertensive rats with hyper-, normo-, and hypoglycemia. Stroke 17, 261–266.PubMedGoogle Scholar
  69. Ito U., Go K. G., Walker J. T., Spatz M., and Klatzo I. (1976) Experimental cerebral ischemia in Mongolian gerbils III. Behaviour of the blood-brain barrier. Acta Neuropathol. (Bed), 34, 1–6.Google Scholar
  70. Kagstrom E., Smith M.-L., and Siesjo B. K. (1983a) Recirculation in the rat brain following incomplete ischemia. J. Cereb. Blood Flow Metab. 3, 183–192.PubMedGoogle Scholar
  71. Kagstrom E., Smith M.-L., and Siesjo B. K. (1983b) Cerebral circulatory responses to hypercapnia and hypoxia in the recovery period following complete and incomplete cerebral ischemia in the rat. Acta Physiol. Scand. 118, 281–291.PubMedGoogle Scholar
  72. Kahn K. (1972) The natural course of experimental cerebral infarction in the gerbil. Neurology 22, 510–515.PubMedGoogle Scholar
  73. Kaneko D., Nakamura N., and Ogawa T. (1985) Cerebral infarction in rats using homologous blood emboli: Development of a new experimental model. Stroke 16, 76–84.PubMedGoogle Scholar
  74. Kass I. S. and Lipton P. (1982) Mechanisms involved in irreversible anoxic damage to the in vitro hippocampal slice. J. Physiol. 332, 459–472.PubMedGoogle Scholar
  75. Kawamoto J. C. and Barrett J. N. (1986) Cryopreservation of primary neurons for tissue culture. Brain Res. 384, 84–93.PubMedGoogle Scholar
  76. Kim S. U., Shin D. H., and Paty D. W. (1984) Long term culture of human oligodendrocytes in serum-free chemically defined medium: A useful model for multiple sclerosis, in Experimental Allergic Encephalomyelitis, Alan R. Liss Inc., New York, pp. 207–214.Google Scholar
  77. Kirino T. (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 239, 57–69.PubMedGoogle Scholar
  78. Kirino T., Tamura A., and Sano K. (1986) A reversible type of neuronal injury following ischemia in the gerbil hippocampus. Stroke 17, 455–459.PubMedGoogle Scholar
  79. Kitagawa K., Matsumoto M., Handa N., Fukunaga R., Ueda A., Isaka Y., Kimura K., and Kamada T. (1989) Prediction of stroke-prone gerbils and their cerebral circulation. Brain Res. 479, 263–269.PubMedGoogle Scholar
  80. Kleihues P. and Hossmann K.-A. (1973) Regional mcorporation of L-[3-H] tyrosine into cat brain proteins after 1 hour of complete ischemia. Acta Neuropathol. 25, 313–324.PubMedGoogle Scholar
  81. Kobayashi M., Lust W. D., and Passonneau J. V. (1977) Concentrations of energy metabolites and cyclic nucleotides during and after bilateral ischemia in the gerbil cerebral cortex. J. Neurochem. 29, 53–59.PubMedGoogle Scholar
  82. Kogure K., Busto R., Scheinberg P. and Reinmuth O. M. (1974) Energy metabolites and water content in rat brain during the early stage of development of cerebral infarction. Brain 97, 103–114.PubMedGoogle Scholar
  83. Kramer W. and Tuynman J. A. (1967) Acute intracranial hypertension: An experimental investigation. Brain Res. 6, 686–705.PubMedGoogle Scholar
  84. Kudo M., Aoyama A., Ichimori S., and Fukunaga N. (1982) An animal model of cerebral infarction. Homologous blood clot emboli in rats. Stroke 13, 505–508.PubMedGoogle Scholar
  85. Kuroiwa T., Bonnekoh P., and Hossmann K.-A. (1990) Prevention of postis-chemic hyperthermia prevents ischemic injury of CA1 neurons in gerbils. J. Cereb. Blood Flow Metab. 10, 550–556.PubMedGoogle Scholar
  86. Laerum O. D., Steinsvag S., and Bjerkvig R. (1985) Cell and tissue culture of the central nervous system: Recent developments and current applications. Acta Neurol. Stand. 72, 529–549.Google Scholar
  87. Langmoen I. A. and Anderson P. (1981) The hippocampal slice in vitro. A description of the technique and some examples of the opportunities it offers, in Electrophysiology of Isolated Mammalian CNS Preparations. (Kerkut G. A. and Wheal H.V., eds.), Academic, London, pp. 51–105.Google Scholar
  88. Levine S. (1960) Anoxic-ischemic encephalopathy in rats. Am. J. Pathol. 36, 1–17.PubMedGoogle Scholar
  89. Levine S. and Payan H. (1966) Effects of ischemia and other procedures on the brain and retina of the gerbil (Meriones unguiculatus). Exp. Neurol. 16, 255–262.PubMedGoogle Scholar
  90. Levine S. and Sohn D. (1969) Cerebral ischemia in infant and adult gerbils: Relation to incomplete circle of Willis. Arch. Pathol. 87, 315–317.PubMedGoogle Scholar
  91. Lipton P. and Whittingham T. S. (1979) The effect of hypoxia on evoked potentials in the in vitro hippocampus. J. Physiol. 287, 427–438.PubMedGoogle Scholar
  92. Lipton P. and Whittingham T. S. (1982) Reduced ATE concentration as a basis for synaptic transmission failure during hypoxia in the in vitro guinea-pig hippocampus. J. Physiol. 287, 427–438.Google Scholar
  93. Lipton P. and Whittingham T. S. (1984) Energy metabolism and brain slice function, in Brain Slices (Dingledine R., ed.), Plenum, New York, pp. 113–153.Google Scholar
  94. Lisak R. P., Pleasure D. E., Silberberg D. H., Manning M. C., and Saida T. (1981) Long term culture of bovine oligodendroglia isolated with percoll gradient. Brain Res. 223, 107–122.PubMedGoogle Scholar
  95. Little J. R. (1977) Implanted device for middle cerebral artery occlusion in conscious cats. Stroke 8, 258–260.PubMedGoogle Scholar
  96. Ljunggren B., Schutz H., and Siesjo B.K. (1974a) Changes in energy state and acid-base parameters of the rat brain during complete compression ischemia. Brain Res. 73, 277–289.PubMedGoogle Scholar
  97. Ljunggren B., Ratcheson R. A., and Siesjo B. K. (1974b) Cerebral metabolic state following complete compression ischemia. Brain Res. 73, 291–307.PubMedGoogle Scholar
  98. Longa E. Z., Weinstein P. R., Carlson S., and Cummins R, (1989) Reversible middle cerebral artery occlusion without craniotomy in rats. Stroke 20, 84–91.PubMedGoogle Scholar
  99. Louis J.-C., Langley K., Anglard P., Wolf M., and Vincendon G. (1983) Long term culture of neurones from human cerebral cortex in serum-free medium. Neurosci. Lett. 41, 313–319.PubMedGoogle Scholar
  100. Lowry O. H., Passonneau J. V., Hasselberger F. X., and Schulz D. W. (1964) Effect of ischemia on known substrates and cofactors of the glycolytic pathway in brain. J. Biol. Chem. 239, 18–30.PubMedGoogle Scholar
  101. Lust W. D., Whittingham T. S., and Passonneau J. V. (1982) Effects of slice thickness and method of preparation on energy metabolism in the in vitro hippocampus. Soc. Neurosci. Abstr. 8, 1000.Google Scholar
  102. Lust W. D., Arai H., Yasumoto Y., Whittingham T. S., Djuricic B., Mrsulja B. B., and Passonneau J. V. (1985) Ischemic encephalopathy, in Cerebral Enery Metabolism and Metabolic Encephalopathy, (McCandless D. W., ed.), Plenum, New York, pp. 79–117.Google Scholar
  103. Lust W. D., Ricci A. J., Selman W. R., and Ratcheson R. A. (1989) Methods of fixation of nervous tissue for use in the study of cerebral energy metabolism, in Neuromethods, vol. 11 (Boulton A. A., Baker G. B., and Butterworth R. F., eds.), Humana, Clifton, NJ., pp. 141.Google Scholar
  104. Manev H., Costa E., Wroblewski J. T., and Guidotti A. (1990) Abusive stimulation of excitatory of amino acid receptors: A strategy to limit neurotoxicity. FASEB/J. 4, 2789–2797.Google Scholar
  105. Mattson M. P. and Kater S. B. (1988) Isolated hippocampal neurons in cryopreserved long-term cultures: Development of neuroarchitecture and sensitivity to NMDA. Int. J. Devl. Neurosci. 6, 439–452.Google Scholar
  106. McKinley J. B., McKinley S. M., and Beaglehole R. (1989) A review of the evidence concerning the impact of medical measures on recent mortality and morbidity in the United States. Int. J. Health Serv. 19, 181–208.Google Scholar
  107. Meller K. and Waelsch M. (1984) Cyclic morphological changes of glial cells in long-term cultures of rat brain. J. Neurocytol. 13, 29–47.PubMedGoogle Scholar
  108. Messing A. and Kim S. U. (1979) Long-term culture of adult mammalian central nervous system neurons. Exp. Neural. 65, 293–300.Google Scholar
  109. Misgeld U. and Frotscher M. (1982) Dependence of the viability of neurons in hippocampal slices on oxygen supply. Brain Res. Bull. 8, 95–100.PubMedGoogle Scholar
  110. Molinarr G. F., Moseley J. I., and Laurent J. P. (1974) Segmental middle cerebra1 artery occlusion in primates: An experimental method requiring minimal surgery and anesthesia. Stroke 5, 334–339.Google Scholar
  111. Molinari G. F. and Laurent J. P. (1976) A classification of experimental models of brain ischemia. Stroke 7, 14–17.Google Scholar
  112. Molinari G. F. (1988) Why model strokes (editorial)? Stroke 19, 1195–1197.PubMedGoogle Scholar
  113. Mortality trends-United States, 1986-1988 (1989) Morbidity and Mortality Weekly Report, 38, pp 117,118.Google Scholar
  114. Moscona A. A. (1961) Rotation-mediated histogenetic aggregation of dissociated cells. Exp. Cell Res. 22, 455–475.PubMedGoogle Scholar
  115. Mrsulja B. B., Mrsulja B. J., Spatz M., and Klatzo I. (1976) Brain serotonin after experimental vascular occlusion. Neurology 26, 785–787.PubMedGoogle Scholar
  116. Murray M. R. and Stout A. P. (1942) Characteristics of human Schwann cells in vitro. Anat. Rec. 84, 275–285.Google Scholar
  117. Murray M. R. and Stout A. P. (1947) Adult human sympathetic ganglion cells cultivated in vitro. Am. J Anat. 80, 225–273.PubMedGoogle Scholar
  118. Murray M. R. (1971) Nervous tissue isolated in culture, in Handbook of Neu-rochemistry, vol. 5A (Lajtha A., ed.), Plenum, New York, pp. 373–438.Google Scholar
  119. Myers R. E. and Yamaguchi M. (1976) Effects of serum glucose concentration on brain response to circulatory arrest. J. Neuropathol. Exp. Neurol. 35, 301.Google Scholar
  120. Nakayama H., Dietrich W. D., Watson B. D., Busto R., and Ginsberg M. D. (1988) Photothrombotic occlusion of rat middle cerebral artery: Histopathological and hemodynamic sequelae of acute recanalization. J. Cereb. Blood Flow Metab. 8, 357–366PubMedGoogle Scholar
  121. Norberg K. and Siesjo B. K. (1975) Cerebral metabolism in hypoxic hypoxia. I. Pattern of activation of glycolysis, a re-evaluation. Brain Res. 86, 31–44.PubMedGoogle Scholar
  122. Nowak T. S. (1985) Synthesis of a stress protein following transient ischemia in the gerbil. J. Neurochem. 45, 1635–1641.PubMedGoogle Scholar
  123. Obrenovitch T. P., Bordi L., Garofalo O., Ono M., Momma F., Bachelard H. S., and Symon L. (1988) In situ freezing of the brain for metabolic studies: Evaluation of the “box” method for large experimental animals. J. Cereb. Blood Flow Metab. 8, 742–749.PubMedGoogle Scholar
  124. O’Brien M. D. and Waltz A. G. (1973) Transorbital approach for occluding the middle cerebral artery without craniectomy. Stroke 4, 201–206.PubMedGoogle Scholar
  125. Okamoto K., Yamori Y., and Nagaoka A. (1974) Establishment of the stroke-prone spontaneously hypertensive rat (SHR). Circ. Res 34-45(Suppl l), I-143–I-153.Google Scholar
  126. Oster-Granite M. L. and Hemdon R. M. (1978) Studies of cultures of human and simian fetal brain cells. I. Characterization of the cell types. Neuropathol. Appl. Neurobiol. 4, 429–442.PubMedGoogle Scholar
  127. Peterson J. N. and Evans J. P. (1937) The anatomical end-results of cerebral arterial occlusion. Trans. Am. Neurol. Assoc. 63, 88–93.Google Scholar
  128. Petito C. K. and Babiak T. (1982) Early proliferative changes in astrocytes in postischemic noninfarcted rat brain. Ann. Neurol 11, 510–518.PubMedGoogle Scholar
  129. Ponten J. and Macintyre E. H. (1968) Long term culture of normal and neo-plastic human glia. Acta Pathol. Microbiol. Scand. 74, 465–486.PubMedGoogle Scholar
  130. Ponten U., Ratcheson R. A., Salford L. G., and Siesjo B. K. (1973) Optimal freezing conditions for cerebral metabolites in rats. J. Neurochem. 21, 1127–1138.PubMedGoogle Scholar
  131. Prado R., Ginsberg M. D., Dietrich W. D., Watson B. D., and Busto R. (1988) Hyperglycemia increases infarct size in collaterally perfused but not end-arterial vascular territories. J. Cereb. Blood Flow Metab. 8, 186–192.PubMedGoogle Scholar
  132. Pulsinelli W. A. and Brierley J. B. (1979) A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 10, 267–272.PubMedGoogle Scholar
  133. Pulsinelli W. A. (1985) Selective neuronal vulnerability: Morphological and molecular characteristics, in Progress in Brain Research, vol. 63 (Kogure K., Hossmann K.-. A., Siesjo B. K., and Welsh F. A., eds.), Elsevier, New York, pp. 2937.Google Scholar
  134. Pulsinelli W. A. and Buchan A. M. (1988) The four-vessel occlusion rat model: Method for complete occlusion of vertebral arteries and control of collateral circulation. Stroke 19, 913,914.Google Scholar
  135. Ratcheson R. A., Bilezikjian L., and Ferrendelli J. A. (1979) The effect of nitrous oxide anesthesia on cerebral energy metabolism. J. Neurochem. 28, 223–225.Google Scholar
  136. Robins M. and Baum H. M. (1981) The national survey of stroke. Incidence. Stroke 12, I-45–I-55.Google Scholar
  137. Roccella E. J. and Lenfant C. (1989) Regional and racial differences among stroke victims in the United States. Clin. Cardiol. 12, 18–22.Google Scholar
  138. Rossen R., Kabat H., and Anderson J. P. (1943) Acute arrest of cerebral circulation in man. Arch. Neurol. Psychiatry 50, 510–528.Google Scholar
  139. Rubino G. J and Young W. (1988) Ischemic cortical lesions after permanent occlusion of individual middle cerebral artery branches in rats. Stroke 19, 870–877.PubMedGoogle Scholar
  140. Rutishauser U., Thiery J.-P., Brackenbury R., and Edelman G. M. (1978) Adhesion among neural cells of the chick embryo. J. Cell Biol. 79, 371–381.PubMedGoogle Scholar
  141. Sacco R. L., Wolf P. A., Kannel W. B., and McNamara P. M. (1982) Survival and recurrence following stroke: The Framingham study. Stroke 13, 290–295.PubMedGoogle Scholar
  142. Salford L. G., Plum F., and Brierley J. B. (1973) Graded hypoxia-oligemia in rat brain. II. Neuropathological alterations and their implications. Arch. Neurol. 29, 234–238.PubMedGoogle Scholar
  143. Schousboe A., Nissen C., Bock E., Sapirstein V. S., Juurlink B. H. J., and Hertz L. (1980) Biochemical development of rodent astrocytes in primary cultures, in Tissue Culture in Neurobiology (Giacobini E., Vernadakis A., and Shahar A., eds.), pp. 3974Google Scholar
  144. Selman W. R., Ricci A. J., Crumrine R. C., LaManna J. C., Ratcheson R. A., and Lust W. D. (1990) The evolution of focal ischemic damage: A metabolic analysis. Metab. Brain Dis. 5, 33–44.PubMedGoogle Scholar
  145. Sensenbrenner M., Labourdette G., Delannoy J. P., Pettman B., Devilliers G., Moonen G., and Bock E. (1980) Morphological and biochemical differentiation of glial cells in primary culture, in Tissue Culture in Neurobiology (Giacobini E., Vemadakis A., and Shahar A., eds.), Raven, New York, pp. 385–Google Scholar
  146. Sheardown M. J., Nielsen E. O., Hansen A. J., Jacobsen P., and Honore T. (1990) 2,3-dihydroxy-nitro-7-sulfamoyl-benzo(F)quinoxaline: A neuroprotectant for cerebral ischenua. Science 247, 571–574.PubMedGoogle Scholar
  147. Shigeno T., Teasdale G. M., McCulloch J., and Graham D. I. (1985) Recirculation model following MCA occlusion in rats. J. Neurosurg. 63, 272–277.PubMedGoogle Scholar
  148. Siemkowicz E. and Hansen A. J. (1978) Clinical restitution following cerebral ischemia in hypo-, normo-and hyperglycemic rats. Acta Neurol. Scand. 58, 1–8.PubMedGoogle Scholar
  149. Simon R. P., Swan J. H., Griffith T., and Meldrum B. S. (1984) Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science 226, 850–852.PubMedGoogle Scholar
  150. Smith M.-L., Auer R. N., and Siesjo B. K. (1984a) The density and distribution of ischemic brain injury in the rat following 2-10 min of forebrain ischemia. Acta Neuropathol. (Berl) 64, 319–332.Google Scholar
  151. Smith M.-L., Bendek G., Dahlgren N., Rosen I., Wieloch T., and Siesjo B. K. (1984b) Models for studying long-term recovery following forebrain ischemia in the rat. 2. A 2-vessel occlusion model. Acta Neurol. Scand., 69, 385–401.PubMedGoogle Scholar
  152. Stemau L. L., Lust, W. D., Ricci A. J., and Ratcheson R. (1989) Role for GABA in selective vulnerability in gerbils. Stroke 20, 281–287.Google Scholar
  153. Sundt T. M. and Waltz A. G. (1966) Experimental cerebral infarction: Retroorbital, extradural approach for occluding the middle cerebral artery. Mayo Clin. Proc. 41, 159–168.PubMedGoogle Scholar
  154. Swaab D. F. and Boer K. (1972) The presence of biologically labile compounds during ischemia and their relationship to the EEG in rat cerebral cortex and hypothalamus. J. Neurochem. 19, 2843–2853.PubMedGoogle Scholar
  155. Symon L. (1974) Physiological studies of blood flow in the middle cerebral artery territory, in Current Concepts of Cerebrovasculur Disease (Stroke), vol. IX, American Heart Assoc., Dallas, pp. 5–8.Google Scholar
  156. Symon L., Dorsch N. W., and Crockard H. A. (1975) The production and clinical features of a chronic stroke model in experimental primates. Stroke 6, 476481.Google Scholar
  157. Takagi S., Cocito S., and Hossmann K.-A. (1977) Blood recirculation and pharmacological responsiveness of the cerebral vasculature following prolonged ischemia of cat brain. Stroke 8, 707–712.PubMedGoogle Scholar
  158. Tamura A., Graham D. I., McCulloch J., and Teasdale G. M. (1981) Focal cerebral ischemia in the rat: 1. Description of technique and early neuropathological consequences followmg middle cerebral artery occlusion. J. Cereb. Blood Flow Metab. 1, 53–60.PubMedGoogle Scholar
  159. Tews J. K., Carter S. H., Roa P. D., and Stone W. E. (1963) Free amino acids and related compounds in dog brain: Post-mortem and anoxic changes, effects of ammonium chloride infusion, and levels during seizures induced by picrotoxrn and by pentylenetetrazol. J. Neurochem. 10, 641–653.PubMedGoogle Scholar
  160. Touzet N., Sensenbrenner M., Lender Th., and Mandel P. (1975) Cultivation and differentiation of dissociated cells of chick embryo encephalon. Differentiation 4, 183–187.Google Scholar
  161. Varon S. and Rainborn C. W. (1969) Dissociation, fractionation, and culture of embryonic brain cells. Brain Res., 12, 180–199.PubMedGoogle Scholar
  162. Walker G. B. and Marx J. L. (1981) The national survey of stroke: Clinical findings. Stroke 12, I-13–I-31.Google Scholar
  163. Waltz A. G. (1978) Clinical relevance of models of cerebral ischemia, in Current Concepts of Cerebrovascular Disease, vol. XII (Waltz A. G., ed.), Amer. Heart Assoc., Dallas, pp. 25–28.Google Scholar
  164. Waltz A. G. (1979) Comparative pathophysiology of ischemic stroke models: An evaluation, in Cerebrovascular Diseases. Eleventh Princeton Conference, (Price T. R. and Nelson E., eds.), Raven, New York, pp. 11–17.Google Scholar
  165. Warburg O. (1923) Versuch an uberlebendem Carcinomgenebe (Methoden). Biochem. Z. 142, 317–333.Google Scholar
  166. Watson B. D., Dietrich W. D., Busto R., Wachtel M. S., and Ginsberg M. D. (1985) Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann. Neurol. 17, 497–504.PubMedGoogle Scholar
  167. Watson B. D., Prado R., Dietrich W. D., Busto R., Scheinberg P., and Ginsberg M. D. (1987) Mitigation of evolving cortical infarction in rats by recombinant tissue plasminogen activator following photochemically induced thrombosis, in Cerebrovascular Diseases. Fifteenth Research (Princeton) Conference (Powers W. J. and Raichle M. E., eds.), Raven, New York, pp. 317–330.Google Scholar
  168. Welsh F. A., Sakamoto T., McKee A. E., and Sims R. (1987) Effect of lactacidosis on pyridine nucleotide stability during ischemia in the mouse brain. J. Neurochem. 49, 846–851.PubMedGoogle Scholar
  169. Welsh F. A., Sims R. E., and Harris V. A. (1990) Mild hypothermia prevents ischemic injury in gerbil hippocampus. J. Cereb. Blood Flow Metab. 10, 557–563.PubMedGoogle Scholar
  170. Werner I., Peterson G. R., and Shuster L. (1971) Choline acetyltransferase and acetylcholinesterase in cultured brain cells from chick embryos. J. Neurochem. 18, 141–151.PubMedGoogle Scholar
  171. Wexler B. C, (1983) Low protein fish vs low protein animal diet enhances the propensity for stroke in stroke-prone/SHR. Stroke 14, 585–590.PubMedGoogle Scholar
  172. Whittingham T. S., Lust W. D., and Passonneau J. V. (1984a) An in vitro model of ischemia: Metabolic and electrical alterations in the hippocam-pal slice. J. Neurosci. 4, 793–802.PubMedGoogle Scholar
  173. Whittingham T. S., Lust W. D., Christakis D. A., and Passonneau J. V. (1984b) Metabolic stability of hippocampal slice preparations during prolonged incubation. J. Neurochem. 43, 689–696.PubMedGoogle Scholar
  174. Whittingham T. S. (1989) The use of hippocampal slices for the study of energy metabolism, in Neuromethods, vol. 11 (Boulton A. A., Baker G. B., and Butterworth R. F., eds.), Humana, Clifton, NJ, pp. 99–132.Google Scholar
  175. Wolf P. A., Kannel W. B., and McGee D. L. (1986) Epidemiology of strokes in North America, in Stroke: Pathophysiology, Diagnosis and Management (Bamett H. J. M., Stein B. M., Mohr J. P., and Yatsu F. M., eds.), Churchill Livingstone, New York, pp. 19–29.Google Scholar
  176. Yamori Y. and Horie R. (1975) Experimental studies on the pathogenesis and prophylaxis of stroke in stroke-prone spontaneously hypertensive rats (SHR). 2. Prophylactic effect of moderate control of blood pressure on stroke. Jpn. Circ. J. 39, 607–611.Google Scholar
  177. Yoshida S., Busto R., Martinez E., Scheinberg P., and Ginsberg M. D. (1985) Regional brain energy metabolism after complete versus incomplete ischemia in the rat in the absence of severe lactic acidosis. J. Cereb. Blood Flow Metab. 5, 490–501.PubMedGoogle Scholar
  178. Zubriggen A., Vandevelde M., Beranek C. F., and Steck A. (1984) Morphological and immunocytochemical characterization of mixed glial cell cultures derived from neonatal canine brain. Res. Vet. Sci. 36, 270–275.Google Scholar

Copyright information

© The Humana Press Inc 1992

Authors and Affiliations

  • Karen A. Seta
    • 1
  • R. Christian Crumrine
    • 1
  • Tim S. Whittingham
    • 1
  • W. David Lust
    • 1
  • David W. McCandless
    • 1
  1. 1.Laboratory of Experimental Neurological SurgeryCase Western Reserve UniversityCIeveland

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