Ultrastructural blood-brain barrier alterations and edema formation in acute spinal cord trauma

Restricted access

✓ Endothelial changes leading to edema formation are examined in the primate spinal cord (Macaca mulatta) following a lesion created by a 20-gm weight falling 15 cm onto the exposed dura. Intravascular perfusion of a paraformaldehyde-glutaraldehyde solution followed by carbon black provides adequate fixation of vascular structures and glial elements. Myelin is poorly preserved. Ultrastructural alterations of the blood-brain barrier consist of loss of integrity of the endothelial tight junctions. Edema caused by vascular disruption and parenchymatous extravasation of intravascular contents is observed along with glial swelling. Interglial gap junctions persist in areas of marked cellular separation and do not impede the migration of edema fluid.

Article Information

Address reprint requests to: W. George Bingham, Jr., M.D., Division of Neurological Surgery, Ohio State University College of Medicine, Room N-911, 410 West Tenth Avenue, Columbus, Ohio 43210.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Photomicrograph of a normal endothelial junction with fusion of external membrane leaflets to form pentalaminar structures at several points along its course. This demonstrates an anatomic substrate of the blood-brain barrier system. L = lumen, P = pericyte, BL = basal lamina. H & E, × 60,000.

  • View in gallery

    Control vessel in white matter showing a prominent collagen (C) containing perivascular space, endothelial junction (arrow), and fibrous glia. H & E, × 4600.

  • View in gallery

    Endothelial junctions with clear separation of unit membrane structure at sites where cytoplasmic density remains (arrows) shows early changes in the blood-brain barrier. Changes of this type occur within 1 ½ minutes following injury. H & E, × 55,000.

  • View in gallery

    Total separation of endothelial junctions with carbon particles present in vascular lumen and extending to basal lamina (BL). H & E, × 35,500.

  • View in gallery

    Early edematous changes in central gray matter near normal-appearing endothelium. Enlarged space occurs between processes in neuropile. Normally with this type of fixation the neuropile contains a small extracellular space with 200 to 400 Å spacing between processes. H & E, × 17,000.

  • View in gallery

    White matter vessel adjacent to area of hemorrhagic necrosis. A dense flocculent material appears in the enlarged extracellular space (ECS) and perivascular space. Swollen glia (G) with dissolution of fibrils is evident. Perivascular structures include smooth muscle (SM), pericyte (P), and collagen (C). H & E, × 4550.

  • View in gallery

    Photomicrograph of edematous area in central gray matter. Gap junctions are maintained (arrows) and retain a septilaminar structure (inset, × 75,000). The extracellular space (ECS) is enlarged and contains proteinaceous material. H & E, × 7500.

  • View in gallery

    Photomicrograph shows central gray matter with swollen glial processes (G). Edema of this type presumably results from altered membrane permeability and fluid influx into the cell. H & E, × 7500.

References

  • 1.

    Albin MSWhite RJAcousta-Rua Get al: Study of functional recovery produced by delayed localized cooling after spinal cord injury in primates. J Neurosurg 29:1131201968Albin MS White RJ Acousta-Rua G et al: Study of functional recovery produced by delayed localized cooling after spinal cord injury in primates. J Neurosurg 29:113–120 1968

  • 2.

    Bodenheimer TSBrightman MW: A blood-brain barrier to peroxidase in capillaries surrounded by perivascular spaces. Am J Anat 122:2492681968Bodenheimer TS Brightman MW: A blood-brain barrier to peroxidase in capillaries surrounded by perivascular spaces. Am J Anat 122:249–268 1968

  • 3.

    Brightman MWKlatzo IOlsson Yet al: The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci 10:2152391970Brightman MW Klatzo I Olsson Y et al: The blood-brain barrier to proteins under normal and pathological conditions. J Neurol Sci 10:215–239 1970

  • 4.

    Brightman MWReese TS: Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40:6486771969Brightman MW Reese TS: Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40:648–677 1969

  • 5.

    Cutler RWPBarlow CF: The effect of hypercapnia on brain permeability to protein. Arch Neurol 14:54631966Cutler RWP Barlow CF: The effect of hypercapnia on brain permeability to protein. Arch Neurol 14:54–63 1966

  • 6.

    Dempsey EWWislocki GB: An electron microscopic study of the blood-brain barrier in the rat, employing silver nitrate as a vital stain. J Biophys Biochem Cytol 1:2452561955Dempsey EW Wislocki GB: An electron microscopic study of the blood-brain barrier in the rat employing silver nitrate as a vital stain. J Biophys Biochem Cytol 1:245–256 1955

  • 7.

    Dohrmann GJWagner FCBucy PC: The microvasculature in transitory traumatic paraplegia. An electron microscopic study in the monkey. J Neurosurg 35:2632711971Dohrmann GJ Wagner FC Bucy PC: The microvasculature in transitory traumatic paraplegia. An electron microscopic study in the monkey. J Neurosurg 35:263–271 1971

  • 8.

    Friend DSGilula NB: Variations in tight and gap junctions in mammalian tissues. J Cell Biol 53:7587751972Friend DS Gilula NB: Variations in tight and gap junctions in mammalian tissues. J Cell Biol 53:758–775 1972

  • 9.

    Hirano ABecker NHZimmerman HM: Pathological alterations in the cerebral endothelial cell barrier to peroxidase. Arch Neurol 20:3003081969Hirano A Becker NH Zimmerman HM: Pathological alterations in the cerebral endothelial cell barrier to peroxidase. Arch Neurol 20:300–308 1969

  • 10.

    Hirano ABecker NHZimmerman HM: The use of peroxidase as a tracer in studies of alterations in the blood-brain barrier. J Neurol Sci 10:2052131970Hirano A Becker NH Zimmerman HM: The use of peroxidase as a tracer in studies of alterations in the blood-brain barrier. J Neurol Sci 10:205–213 1970

  • 11.

    Johansson BLi GLOlsson Yet al: The effect of acute arterial hypertension on the blood-brain barrier to protein tracers. Acta Neuropathol 16:1171241970Johansson B Li GL Olsson Y et al: The effect of acute arterial hypertension on the blood-brain barrier to protein tracers. Acta Neuropathol 16:117–124 1970

  • 12.

    Karlsson USchultz RL: Fixation of the central nervous system for electron microscopy by aldehyde perfusion. I. Preservation with aldehyde perfusates versus direct perfusion with osmium tetroxide with special reference to membranes and the extracellular space. J Ultrastruct Res 12:1601861965Karlsson U Schultz RL: Fixation of the central nervous system for electron microscopy by aldehyde perfusion. I. Preservation with aldehyde perfusates versus direct perfusion with osmium tetroxide with special reference to membranes and the extracellular space. J Ultrastruct Res 12:160–186 1965

  • 13.

    Karnovsky MJ: A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J Cell Biol 27:137A November 1965(Abstract No. 270)Karnovsky MJ: A formaldehyde-glutaraldehyde fixative of high osmolarity for use in electron microscopy. J Cell Biol 27:137A November 1965 (Abstract No. 270)

  • 14.

    Karnovsky MJ: The ultrastructural basis of capillary permeability studied with peroxidase as a tracer. J Cell Biol 35:2132361967Karnovsky MJ: The ultrastructural basis of capillary permeability studied with peroxidase as a tracer. J Cell Biol 35:213–236 1967

  • 15.

    King LS: Some aspects of the hematoencephalic barrier. Proc Assoc Res Nerv Ment Dis 18:1501771938King LS: Some aspects of the hematoencephalic barrier. Proc Assoc Res Nerv Ment Dis 18:150–177 1938

  • 16.

    Klatzo I: Presidential address. Neuropathological aspects of brain edema. J Neuropathol Exp Neurol 26:1141967Klatzo I: Presidential address. Neuropathological aspects of brain edema. J Neuropathol Exp Neurol 26:1–14 1967

  • 17.

    Klatzo IPiraux ALaskowski EJ: The relationship between edema, blood-brain barrier and tissue elements in local brain injury. J Neuropathol Exp Neurol 17:5485641958Klatzo I Piraux A Laskowski EJ: The relationship between edema blood-brain barrier and tissue elements in local brain injury. J Neuropathol Exp Neurol 17:548–564 1958

  • 18.

    Kung PCLee JCBakay L: Electron microscopic study of experimental acute hypertensive encephalopathy. Acta Neuropathol 10:2632721968Kung PC Lee JC Bakay L: Electron microscopic study of experimental acute hypertensive encephalopathy. Acta Neuropathol 10:263–272 1968

  • 19.

    Lee JCBakay L: Ultrastructural changes in the edematous central nervous system. II. Cold induced edema. Arch Neurol 14:36491966Lee JC Bakay L: Ultrastructural changes in the edematous central nervous system. II. Cold induced edema. Arch Neurol 14:36–49 1966

  • 20.

    Majno GPalade GE: Studies on inflammation. 1. The effect of histamine and serotonin on vascular permeability: An electron microscopic study. J Biophys Biochem Cytol 11:5716051961Majno G Palade GE: Studies on inflammation. 1. The effect of histamine and serotonin on vascular permeability: An electron microscopic study. J Biophys Biochem Cytol 11:571–605 1961

  • 21.

    Olsson YHossman KA: Fine structural localization of exudated protein tracers in the brain. Acta Neuropathol 16:1031161970Olsson Y Hossman KA: Fine structural localization of exudated protein tracers in the brain. Acta Neuropathol 16:103–116 1970

  • 22.

    Pappas GD: Some morphological considerations of the blood-brain barrier. J Neurol Sci 10:2412461970Pappas GD: Some morphological considerations of the blood-brain barrier. J Neurol Sci 10:241–246 1970

  • 23.

    Pappas GDAsada YBennet MVL: Morphological correlates of increased coupling resistance at an electronic synapse. J Cell Biol 49:1731881971Pappas GD Asada Y Bennet MVL: Morphological correlates of increased coupling resistance at an electronic synapse. J Cell Biol 49:173–188 1971

  • 24.

    Reese TSKarnovsky MJ: Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:2072171967Reese TS Karnovsky MJ: Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:207–217 1967

  • 25.

    Reynolds ES: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:2082151963Reynolds ES: The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208–215 1963

  • 26.

    Rinder LOlsson Y: Studies on vascular permeability changes in experimental brain concussion. I. Distribution of circulating fluorescent indicators in brain and cervical cord after sudden mechanical loading of the brain. Acta Neuropathol 11:1832001968Rinder L Olsson Y: Studies on vascular permeability changes in experimental brain concussion. I. Distribution of circulating fluorescent indicators in brain and cervical cord after sudden mechanical loading of the brain. Acta Neuropathol 11:183–200 1968

  • 27.

    Rinder LOlsson Y: Studies on vascular permeability changes in experimental brain concussion. II. Duration of altered permeability. Acta Neuropathol 11:2012091968Rinder L Olsson Y: Studies on vascular permeability changes in experimental brain concussion. II. Duration of altered permeability. Acta Neuropathol 11:201–209 1968

  • 28.

    Torack RMTerry RDZimmerman HM: The fine structure of cerebral fluid accumulation. I. Swelling secondary to cold injury. Am J Pathol 35:113511471959Torack RM Terry RD Zimmerman HM: The fine structure of cerebral fluid accumulation. I. Swelling secondary to cold injury. Am J Pathol 35:1135–1147 1959

  • 29.

    Van Harreveld ACrowell JMalhotra SK: A study of extracellular space in central nervous tissue by freeze-substitution. J Cell Biol 25:1171371965Van Harreveld A Crowell J Malhotra SK: A study of extracellular space in central nervous tissue by freeze-substitution. J Cell Biol 25:117–137 1965

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 52 52 5
Full Text Views 262 262 0
PDF Downloads 88 88 0
EPUB Downloads 0 0 0

PubMed

Google Scholar