Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures

Abstract

Brain blood vessels constitute a micrometer-scale vascular network responsible for supply of oxygen and nutrition. In this study, we analyzed cerebral tissues of the anterior cingulate cortex and superior temporal gyrus of schizophrenia cases and age/gender-matched controls by using synchrotron radiation microtomography or micro-CT in order to examine the three-dimensional structure of cerebral vessels. Over 1 m of cerebral blood vessels was traced to build Cartesian-coordinate models, which were then used for calculating structural parameters including the diameter and curvature of the vessels. The distribution of vessel outer diameters showed a peak at 7–9 μm, corresponding to the diameter of the capillaries. Mean curvatures of the capillary vessels showed a significant correlation to the mean curvatures of neurites, while the mean capillary diameter was almost constant, independent of the cases. Our previous studies indicated that the neurites of schizophrenia cases are thin and tortuous compared to controls. The curved capillaries with a constant diameter should occupy a nearly constant volume, while neurons suffering from neurite thinning should have reduced volumes, resulting in a volumetric imbalance between the neurons and the vessels. We suggest that the observed structural correlation between neurons and blood vessels is related to neurovascular abnormalities in schizophrenia.

Microvascular imaging of the unstained human superior colliculus using synchrotron-radiation phase-contrast microtomography

“…2 B). The peak of the vessel diameter is between 8.6–10.2 µm, which is in accordance with a recent study that used absorption-contrast microtomography on silver impregnated human brain 21 .

Figure 2 Microvasculature segmented from 0.94 µm voxel size phase-contrast microtomography.

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“…2 A and in supplementary video , vessels with different size of diameters are successfully extracted. Similar to prior work on post mortem human cortex 21 , 24 , the vessel diameter distribution shows a long tail towards larger vessels (Fig. 2 B).…”

“…Earlier studies that injected contrast agent into the vasculature suggested the capillary diameter to be about 7–7.5 µm 9 or 6.47 µm 7 . More recently, a synchrotron radiation imaging of a Golgi impregnated human neocortex found the capillary diameter to be 7–9 µm 21 , consistent with our results of unstained superior colliculus where the most frequently observed vessel diameter was between 8.6–10.2 µm. The slight difference in capillary diameter can depend on whether the capillary wall has been included or not.…”

“…In the studies of Reina-De La Torre et al 9 and Lauwers et al 7 a contrast agent was used as the source for vascular information and their results likely represent the inner diameter of the capillaries. On the other hand, the results from Saiga et al 21 and our study probably include the capillary walls resulting in the outer diameter of the capillaries.…”

“…Preliminary results suggest that some vessel detail is also possible to discern in mouse spinal cord after perfusion even in absence of contrast agents 18 . For human brain tissue, many groups prefer to use stains for increased tissue contrast 19 – 21 . Only a few studies describe PC-μCT results for vascular imaging of unstained human brain 22 , 23 .…”