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Electron microscope studies of cerebral swelling

I. Studies on the permeability of brain capillaries, using ferritin molecules as tracers

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Summary

Ferritin particles which have been injected intravenously pass through the endothelial cell by pinocytosis in both normal and swollen brain tissue.

In normal brain tissue, ferritin particles do not reach the plasma membrane of the perivascular astrocyte, even three hours after injection. A gradient of distribution of the ferritin may be noted and the concentration of the substance falls off sharply as one approaches the endothelial basement membrane.

The subpial marginal astrocytes are capable of ingesting ferritin particles injected either intravenously or intrathecally.

In cerebral swelling resulting from compression produced by inflation of an extradural balloon, ferritin particles may be seen to pass through the basement membrane of the endothelial cell into the cytoplasm of the perivascular astrocyte. These particles are located chiefly in dense bodies and to some extent in vesicles and mitochondria with regressive appearance. In the white matter in the late stage of brain swelling, ferritin may be seen free in the distended extracellular spaces.

We speculate that the blood-brain barrier mechanism under normal circumstances is a complex function in which the endothelial cell serves as a selecting valve, the basement membrane serves as a principal filter, and the perivascular astrocyte monitors the process. Under the abnormal circumstances that develop in association with experimentally produced cerebral swelling, these specific functions, which as a group constitute the blood-brain barrier, are distorted, as evidenced by the ferritin tracer studies, and increased fluid content develops in the white matter.

Zusammenfassung

Intravenös injizierte Ferritinteilchen treten sowohl im normalen als auch im ödematösen Hirngewebe mittels Pinocytose durch die Endothelzelle.

Im normalen Hirngewebe erreichen die Ferritinteilchen die Plasmamembran der perivaskulären Astrocyten auch 3 Std nach der Injektion nicht. Das Verteilungsgefälle des Ferritins kann registriert werden; seine Konzentration sinkt in die Nähe der Basalmembran stark ab. Die subpialen, randständigen Astrocyten sind imstande, intravenös oder intrathecal injizierte Ferritinteilchen aufzunehmen.

Bei Hirnschwellung, die durch Kompression mittels Aufblasen eines extradurallen Ballons entsteht, kann man Ferritinteilchen durch die Basalmembran der Endothelzellen in das Cytoplasma perivaskulärer Astrocyten eintreten sehen. Diese Teilchen liegen hauptsächlich in “dense bodies” und zu einem gewissen Anteil auch in Bläschen und in regressiv veränderten Mitochondrien. Im Spätstadium von Hirnschwellung kann Ferritin frei in den erweiterten Extracellulärräumen festgestellt werden. Wir vermuten, daß der Blut-Hirn-Schraken-Mechanismus unter normalen Umständen ein Funktionsgefüge darstellt, innerhalb welchem die Endothelzelle als Wählerventil, die Basalmembran als Hauptfilter und der perivaskuläre Astrocyt als Kontrollinstanz fungieren. Unter abnormen Bedingungen im Zusammenhang mit experimentell erzeugter Hirnschwellung werden diese spezifischen Funktionen, welche gemeinsam die Blut-Hirn-Schranke ausmachen, verzerrt, wie durch die Ferritinmarkierungs-Untersuchungen und die Erhöhung des Flüssigkeitsgehaltes im Mark bewiesen wird.

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Aided by Grants from the Douglas Smith Foundation, the Simms Research Foundation, and the Junior Auxiliary of the University of Chicago Cancer Research Foundation

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Tani, E., Evans, J.P. Electron microscope studies of cerebral swelling. Acta Neuropathol 4, 507–526 (1965). https://doi.org/10.1007/BF00688511

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Keywords

  • White Matter
  • Basement Membrane
  • Ferritin
  • Dense Body
  • Normal Brain Tissue