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Comparative Study
. 2018 Apr;301(4):697-710.
doi: 10.1002/ar.23728. Epub 2017 Dec 1.

The Cellular Composition and Glia-Neuron Ratio in the Spinal Cord of a Human and a Nonhuman Primate: Comparison With Other Species and Brain Regions

Jami Bahney  1 , Christopher S von Bartheld  1
Affiliations
Comparative Study

The Cellular Composition and Glia-Neuron Ratio in the Spinal Cord of a Human and a Nonhuman Primate: Comparison With Other Species and Brain Regions

Jami Bahney et al. Anat Rec (Hoboken). 2018 Apr.

Abstract

The cellular composition of brains shows largely conserved, gradual evolutionary trends between species. In the primate spinal cord, however, the glia-neuron ratio was reported to be greatly increased over that in the rodent spinal cord. Here, we re-examined the cellular composition of the spinal cord of one human and one nonhuman primate species by employing two different counting methods, the isotropic fractionator and stereology. We also determined whether segmental differences in cellular composition, possibly reflecting increased fine motor control of the upper extremities, may explain a sharply increased glia-neuron ratio in primates. In the cynomolgus monkey spinal cord, the isotropic fractionator and stereology yielded 206-275 million cells, of which 13.3-25.1% were neurons (28-69 million). Stereological estimates yielded 21.1% endothelial cells and 65.5% glial cells (glia-neuron ratio of 4.9-5.6). In human spinal cords, the isotropic fractionator and stereology generated estimates of 1.5-1.7 billion cells and 197-222 million neurons (13.4% neurons, 12.2% endothelial cells, 74.8% glial cells), and a glia-neuron ratio of 5.6-7.1, with estimates of neuron numbers in the human spinal cord based on morphological criteria. The non-neuronal to neuron ratios in human and cynomolgus monkey spinal cords were 6.5 and 3.2, respectively, suggesting that previous reports overestimated this ratio. We did not find significant segmental differences in the cellular composition between cervical, thoracic and lumbar levels. When compared with brain regions, the spinal cord showed gradual increases of the glia-neuron ratio with increasing brain mass, similar to the cerebral cortex and the brainstem. Anat Rec, 301:697-710, 2018. © 2017 Wiley Periodicals, Inc.

Keywords: evolution; glia neuron ratio; human; isotropic fractionator; primate; quantification; spinal cord; stereology.

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Figures

Fig. 1
Fig. 1
Distribution of nuclei in the z-axis of tissue sections. The center of the nucleus of 345 cells was measured in 18 sections, and their distribution was plotted for 10-percentile bins, with the “10” percentile bin being the top of the tissue section (against the cover glass), and the bottom (“100”) percentile bin adjacent to the glass slide. There was no loss of caps at the tissue margins, but rather an increased density of nuclei, indicating differential compression. The measurements for human tissue sections (mean final thickness of 31.4 μm) of the spinal cord are shown, and the z-axis analysis was similar for monkey sections. Accordingly, no guard zones were used, since they would have caused an underestimate due to predominant sampling in the low-density core of the tissue section.
Fig. 2
Fig. 2
The three pairs of graphs demonstrate the differences between the glia-neuron ratio (GNR) and the non-neuronal to neuron ratio (nNNR), exemplified for three brain structures: Cerebral Cortex, Cerebellum and “Rest of Brain” (Diencephalon and Brainstem). Histological counting methods such as stereology determine the number of neurons (blue) and glial cells (red), while the isotropic fractionator (IF) determines numbers of neurons and non-neuronal cells, the latter being composed of both glial (red) and endothelial cells (green). Since the endothelial cells make up between 12% and 30% of all non-neuronal cells, the nNNR is only modestly larger than the GNR, as illustrated in three typical examples: Cerebral cortex, brainstem, and cerebellum. The numbers of the three cell types are chosen to demonstrate simple math and ratios, but roughly reflect the known ratios in the selected three brain regions. Note that the nNNR increases over the GNR merely from 2 to 3 in cortex, from 10 to 15 in rest of brain, and from 0.1 to 0.25 in cerebellum.
Fig. 3A–D
Fig. 3A–D
Representative photomicrographs of neurons, glial cells and endothelial cells in the spinal cord of cynomolgus monkey (A–B) and human spinal cord (C–D). Panels A, B and C show neurons and glial cells, panels A, B and D show endothelial cells (indicated by arrows). Panels A and B are from the ventral horn in the cervical spinal cord, panel C is from the ventral horn of the thoracic cord, and panel D is from the white matter of the thoracic cord (anterior corticospinal tract). Paraffin-embedded tissue sections were stained with hematoxylin-eosin. Scale bar (shown in panel C, same magnification for all panels) = 20 μm. Note that in panels A and B, all blood vessels (including capillaries) show a distinct orange color, unlike the pink neuropil, thereby facilitating the identification of endothelial cells.
Fig. 4A–F
Fig. 4A–F
Comparison of trends of glia-neuron ratios (GNRs) and non-neuronal to neuron ratios (nNNRs) for different CNS structures in vertebrate species, plotted as a function of mass of brain (MB) on a logarithmic scale. A, GNR for Cerebral Cortex; B, nNNR for Cerebral Cortex; C, nNNR for Cerebellum; D, nNNR for Rest of Brain; E, GNR for Spinal Cord; F, nNNR for Spinal Cord. Note that for cerebral cortex and rest of brain, as well as spinal cord, there is an obvious increase in the GNR and nNNR from smaller to larger brains with slopes of +0.25 to +0.93, but not for cerebellum where the ratio is not correlated with brain size: MB, mass of brain. Note that the y-axis shows different ranges of GNRs and nNNRs between panels. Slopes for GNRs and nNNRs are generally similar, except for the outliers (indicated by red squares) in panels B and D (both for African Elephant), and the non-human primate data from the study by Burish et al., 2010 in panel F. The data obtained in the current study are indicated by green circles in panels E and F. Two data points are shown for each of the two primate species we examined, reflecting the two methods used. When slopes were calculated with one combined (average) data point for each species, the slopes were virtually identical to the ones shown. For sources of other data points, see Tables 3 and 4.
Fig. 5
Fig. 5
Cellular composition of the spinal cord in cynomolgus monkey and human compared with the composition in an entire human brain, showing the relative percentage of neurons (blue), glial cells (red) and endothelial cells (green), based on the data obtained in the current study. Approximate percentages are indicated on the columns. The bar for the entire human brain adds to 99%, not 100%, due to rounding. The cellular composition in the spinal cord differed considerably from that in the entire brain, and was most similar to the composition found in the brainstem (“rest of brain”) (compare Fig. 5 with Fig. 2).
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