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Brief Hypoxia-Ischemia Initially Damages Cerebral Neurons

Brief Hypoxia-Ischemia Initially Damages Cerebral Neurons Abstract Rats were studied during cerebral hypoxic ischemia to determine whether neurons or blood vessels suffered the first damage. Ten or more minutes of unilateral carotid artery occlusion combined with systemic hypoxemia (PaO2, 21 mm Hg) produced neuronal but not vascular damage in the ipsilateral cerebral hemispheres of 18 of 29 rats (62%); two and five minute stresses caused no visible neuronal abnormalities. The longer exposures produced more widespread damage, and neuronal loss and gliomesodermal reaction were evident after prolonged survival. Early neuronal changes correlated with abnormalities of motor behavior (P <.005). Despite neuronal damage that was sometimes extensive, vascular no-reflow developed in only one of 24 animals after 20 and 30 minutes of hypoxia-ischemia. Production of neuronal and neurological abnormalities in the absence of hypotension or vascular no-reflow indicates that hypoxia-ischemia initially damaged cerebral neurons. References 1. Schneider M: Critical blood pressure in the cerebral circulation , in Schade JP, McMenemey WH (eds): Selective Vulnerability of the Brain in Hypoxaemia . Oxford, England, Blackwell Scientific Publications, 1963, pp 7-20. 2. Ames A III, Wright RL, Kowada M, et al: Cerebral ischemia: II. The no-reflow phenomenon . Am J Pathol 52:437-453, 1968. 3. Levine S: Anoxic-ischemic encephalopathy in rats . Am J Pathol 36:1-17, 1960. 4. Salford L, Plum F, Siesjö B: Graded hypoxia-oligemia in rat brain: I. Biochemical alterations and their implications . Arch Neurol 29:227-233, 1973.Crossref 5. Salford L, Plum F, Brierley JB: Graded hypoxia-oligemia in rat brain: II. Neuropathological alterations and their implications . Arch Neurol 29:234-238, 1973.Crossref 6. Brown AW, Brierley JB: The nature, distribution and earliest stages of anoxic-ischaemic nerve cell damage in the rat brain as defined by the optical microscope . Br J Exp Pathol 49:87-106, 1968. 7. Cammermeyer J: Nonspecific changes of the central nervous system in normal and experimental material , in Bourne GH (ed): The Structure and Function of Nervous Tissue . New York, Academic Press Inc, 1972, vol 6, pp 131-251. 8. Nicholson AN, Freeland SA, Brierley JB: A behavioral and neuropathological study of the sequelae of profound hypoxia . Brain Res 22:327-345, 1970.Crossref 9. Spielmeyer W: Histopathologie des Nervensystems . Berlin, Springer Verlag, 1922. 10. Cammermeyer J: "Ischemic neuronal disease" of Spielmeyer: A reeveluation . Arch Neurol 29:391-393, 1973.Crossref 11. Brierley JB, Meldrum BS, Brown AW: The threshold and neuropathology of cerebral "anoxic-ischemic" cell change . Arch Neurol 29:367-373, 1973.Crossref 12. Brown AW, Brierley JB: The earliest alterations in rat neurones after anoxia-ischemia . Acta Neuropathol 23:9-22, 1973.Crossref 13. Cantu R, Ames A III, Di Giacinto G, et al: Hypotension: A major factor limiting recovery from cerebral ischemia . J Surg Res 9:525-529, 1969.Crossref 14. Leaf A: Cell swelling: A factor in ischemic tissue injury . Circulation 48:455-458, 1973.Crossref 15. Fischer EG, Ames A III: Studies on mechanisms of impairment of cerebral circulation following ischemia: Effect of hemodilution and perfusion pressure . Stroke 3:538-542, 1972.Crossref 16. Barnhart MI, Walsh RT, Gilroy J: Formal discussion, in McDowell FH, Brennan RW (eds): Eighth Conference Cerebral Vascular Diseases. New York, Grune & Stratton, 1973, pp 300-306. 17. Ljunggren B, Brierley JB, Siesjö BK: Neuropathological alterations in rat brain after complete ischemia due to raised intracranial pressure. Proceedings 2nd International Symposium on Intracranial Pressure. Lund, Sweden, 1974, to be published. 18. Hossmann K-A, Kleihues P: Reversibility of ischemic brain damage . Arch Neurol 29:375-382, 1973.Crossref 19. Sobotka P, Jirasek A, Gebert E: Morphological consequences of prolonged complete brain ischemia . Brain Res 79:111-118, 1974.Crossref 20. Brierley JD, Adams JH, Graham DI, et al: Neocortical death after cardiac arrest . Lancet 2:560-565, 1971. 21. Jennett B, Plum F: Persistent vegetative state after brain damage . Lancet 1:734-737, 1972.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Brief Hypoxia-Ischemia Initially Damages Cerebral Neurons

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Publisher
American Medical Association
Copyright
Copyright © 1975 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1975.00490490054004
Publisher site
See Article on Publisher Site

Abstract

Abstract Rats were studied during cerebral hypoxic ischemia to determine whether neurons or blood vessels suffered the first damage. Ten or more minutes of unilateral carotid artery occlusion combined with systemic hypoxemia (PaO2, 21 mm Hg) produced neuronal but not vascular damage in the ipsilateral cerebral hemispheres of 18 of 29 rats (62%); two and five minute stresses caused no visible neuronal abnormalities. The longer exposures produced more widespread damage, and neuronal loss and gliomesodermal reaction were evident after prolonged survival. Early neuronal changes correlated with abnormalities of motor behavior (P <.005). Despite neuronal damage that was sometimes extensive, vascular no-reflow developed in only one of 24 animals after 20 and 30 minutes of hypoxia-ischemia. Production of neuronal and neurological abnormalities in the absence of hypotension or vascular no-reflow indicates that hypoxia-ischemia initially damaged cerebral neurons. References 1. Schneider M: Critical blood pressure in the cerebral circulation , in Schade JP, McMenemey WH (eds): Selective Vulnerability of the Brain in Hypoxaemia . Oxford, England, Blackwell Scientific Publications, 1963, pp 7-20. 2. Ames A III, Wright RL, Kowada M, et al: Cerebral ischemia: II. The no-reflow phenomenon . Am J Pathol 52:437-453, 1968. 3. Levine S: Anoxic-ischemic encephalopathy in rats . Am J Pathol 36:1-17, 1960. 4. Salford L, Plum F, Siesjö B: Graded hypoxia-oligemia in rat brain: I. Biochemical alterations and their implications . Arch Neurol 29:227-233, 1973.Crossref 5. Salford L, Plum F, Brierley JB: Graded hypoxia-oligemia in rat brain: II. Neuropathological alterations and their implications . Arch Neurol 29:234-238, 1973.Crossref 6. Brown AW, Brierley JB: The nature, distribution and earliest stages of anoxic-ischaemic nerve cell damage in the rat brain as defined by the optical microscope . Br J Exp Pathol 49:87-106, 1968. 7. Cammermeyer J: Nonspecific changes of the central nervous system in normal and experimental material , in Bourne GH (ed): The Structure and Function of Nervous Tissue . New York, Academic Press Inc, 1972, vol 6, pp 131-251. 8. Nicholson AN, Freeland SA, Brierley JB: A behavioral and neuropathological study of the sequelae of profound hypoxia . Brain Res 22:327-345, 1970.Crossref 9. Spielmeyer W: Histopathologie des Nervensystems . Berlin, Springer Verlag, 1922. 10. Cammermeyer J: "Ischemic neuronal disease" of Spielmeyer: A reeveluation . Arch Neurol 29:391-393, 1973.Crossref 11. Brierley JB, Meldrum BS, Brown AW: The threshold and neuropathology of cerebral "anoxic-ischemic" cell change . Arch Neurol 29:367-373, 1973.Crossref 12. Brown AW, Brierley JB: The earliest alterations in rat neurones after anoxia-ischemia . Acta Neuropathol 23:9-22, 1973.Crossref 13. Cantu R, Ames A III, Di Giacinto G, et al: Hypotension: A major factor limiting recovery from cerebral ischemia . J Surg Res 9:525-529, 1969.Crossref 14. Leaf A: Cell swelling: A factor in ischemic tissue injury . Circulation 48:455-458, 1973.Crossref 15. Fischer EG, Ames A III: Studies on mechanisms of impairment of cerebral circulation following ischemia: Effect of hemodilution and perfusion pressure . Stroke 3:538-542, 1972.Crossref 16. Barnhart MI, Walsh RT, Gilroy J: Formal discussion, in McDowell FH, Brennan RW (eds): Eighth Conference Cerebral Vascular Diseases. New York, Grune & Stratton, 1973, pp 300-306. 17. Ljunggren B, Brierley JB, Siesjö BK: Neuropathological alterations in rat brain after complete ischemia due to raised intracranial pressure. Proceedings 2nd International Symposium on Intracranial Pressure. Lund, Sweden, 1974, to be published. 18. Hossmann K-A, Kleihues P: Reversibility of ischemic brain damage . Arch Neurol 29:375-382, 1973.Crossref 19. Sobotka P, Jirasek A, Gebert E: Morphological consequences of prolonged complete brain ischemia . Brain Res 79:111-118, 1974.Crossref 20. Brierley JD, Adams JH, Graham DI, et al: Neocortical death after cardiac arrest . Lancet 2:560-565, 1971. 21. Jennett B, Plum F: Persistent vegetative state after brain damage . Lancet 1:734-737, 1972.Crossref

Journal

Archives of NeurologyAmerican Medical Association

Published: Jul 1, 1975

References