1 The morphological consequences of hypobaric hypox ia, exposure to reduced pressure atmospheres, were examined in the hippocampus of male Fischer 344 rats. Severe chronic hypoxia can produce permanent neuronal damage with hippocampal structures being especially vulnerable. 2 Hippocampal morphology was studied using histolo gical observations after a 4 day exposure to sea level, 5500 m, or 6400 m. Two groups tested at 6400 m were sacrificed at different intervals following exposure, 72 and 144 h, to examine the effect of post-exposure time on neuronal damage. 3 Histological damage was observed in rats' brains following exposure to altitude, with cell degeneration and death increasing as altitude increased. In addition, it was found that the longer the time following exposure before sacrifice, the more noticeable the damage, suggest ing delayed neurotoxicity. Increases in the number of damaged cells following altitude were significant for the CA3 region of one 6400 m group; however, other differ ences did not reach statistical significance. Rats exposed to altitude for 4 days ate less and lost significantly more weight than did animals at sea level. 4 It appears that 4 days of exposure to altitudes less than or equal to 6400 m does produce changes in the CA3 subfield, but the damage is different than that seen with other models of non-transient ischemia.

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A method has been developed for separation of erythrocytes on the basis of size using counterflow centrifugation. Human red blood cells with an original mean corpuscular volume (MCV) of 89.2 +/- 4.1 fl were isolated, free of plasma proteins and other cell contaminants, into seven fractions ranging in size from 77.0 +/- 2.7 fl to 98.5 +/- 4.8 fl. The ratio of the age-related enzyme, erythrocyte glutamic oxaloacetic transferase (EGOT), to hemoglobin (Hb) increased progressively through the fractions, suggesting a correlation between erythrocyte volume and age. Reticulocytes, though present in all fractions, were selectively enriched in the larger subpopulations. To verify the biochemical evidence that erythrocytes decrease in volume with aging, in vivo cohort labeling of red blood cells with 59Fe was performed in baboons. A similar relationship of EGOT to Hb was observed to that in the human subpopulations. The peak activity of 59Fe/RBC appeared initially in the red blood cells with the highest MCV and progressed from the erythrocytes with the largest MCV to the erythrocytes with the smallest MCV over the next 10-12 weeks, confirming the hypothesis that red blood cells decrease in volume as they age. The technique of counterflow centrifugation appears to provide a simple, rapid, and reproducible method for the separation of erythrocytes on the basis of size.

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