Interpretation of Hyperchromic Nerve Cells: Relative Significance of the Type of Fixative Used, of the Osmolarity of the Cytoplasm and the Surrounding Fluid in the Production of Cell Shrinkage.

Contradictory opinions have been expressed as to the significance of the hyperchromic, shrunken cells (Flesch, 1887) which are often found in normal animal brains and, under certain conditions, in human material. Nissl (1896) considered hyperchromic cells artifacts; Cajal ('09) resting cells; Dolley ('10) to represent initial stages of fatigue; Fortuyn ('27) functional stages; Einarson ('49a and b) hyperactive cells; Scharrer ('33, '37, ' 3 8 ) mechanical artifacts; and Cammermeyer ('60b, '61) products of postmortem traumatization and consequent fixation. Furthermore, many investigators reported on these cells in experimental and human pathological material, interpreting them as pathological changes. Numerous references are found in the review by Miller ('49) and in Cammermeyer's ('60, a and b, '61) recent papers. Many such painstakingly executed studies indicate the conditions under which hyperchromic cells can be produced or avoided. Few, however, offer clues as to the precise mechanism responsible for the volume change. A cell filled with, and surrounded by, fluid cannot simply "collapse" (Cammermeyer, '60b) unless there is either damage to the membrane with outflow of cytoplasm or a shift of the osmotic equilibrium. Likewise, there is no known colloid which shrinks to a fraction of its volume (Cotte, '57; Picard and Cotte, ' 5 7 ) upon minimal mechanical stimulation but retains its volume if not stimulated. Osmotic changes during fixation have been studied to a considerable extent (Fortuyn, '24, '27; Koenig, Groat, and Windle, '45; and others), but a generalization based on this data is not possible unless one knows whether and to what extent the cell membrane is affected by the fixative. The latter question cannot be clarified in a complex tissue; thus, the sample experiments with red blood cells reported below were thought necessary to investigate differences in the mode of action of the fixative on the cell membrane. There were indications that hyperchromasia of nerve cells and crenation of erythrocytes were closely related phenomena. This study, thus, represents an effort toward a better understanding of the mode of action of fixatives, the significance of mechanical damage to the tissue, and the interaction of these factors in the production of hyperchromic, shrunken cells. A variety of experiments was used to analyze the complex interactions of osmotic changes, dependent upon the osmotic state of the cell's cytoplasm, the osmotic concentration of the surrounding fluid, and the type of fixation used.