Structural and ultrastructural alterations in human olfactory pathways and possible associations with herpesvirus 6 infection

Publisher Copyright: © 2017 Skuja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them.publishersversionPeer reviewe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Prospects of Photo- and Thermoacoustic Imaging in Neurosurgery

The evolution of neurosurgery has been, and continues to be, closely associated with innovations in technology. Modern neurosurgery is wed to imaging technology and the future promises even more dependence on anatomic and, perhaps more importantly, functional imaging. The photoacoustic phenomenon was described nearly 140 yr ago; however, biomedical applications for this technology have only recently received significant attention. Light-based photoacoustic and microwave-based thermoacoustic technologies represent novel biomedical imaging modalities with broad application potential within and beyond neurosurgery. These technologies offer excellent imaging resolution while generally considered safer, more portable, versatile, and convenient than current imaging technologies. In this review, we summarize the current state of knowledge regarding photoacoustic and thermoacoustic imaging and their potential impact on the field of neurosurgery

Prospects of Photo- and Thermoacoustic Imaging in Neurosurgery

The evolution of neurosurgery has been, and continues to be, closely associated with innovations in technology. Modern neurosurgery is wed to imaging technology and the future promises even more dependence on anatomic and, perhaps more importantly, functional imaging. The photoacoustic phenomenon was described nearly 140 yr ago; however, biomedical applications for this technology have only recently received significant attention. Light-based photoacoustic and microwave-based thermoacoustic technologies represent novel biomedical imaging modalities with broad application potential within and beyond neurosurgery. These technologies offer excellent imaging resolution while generally considered safer, more portable, versatile, and convenient than current imaging technologies. In this review, we summarize the current state of knowledge regarding photoacoustic and thermoacoustic imaging and their potential impact on the field of neurosurgery

Intracerebral Delivery of Brain-Derived Neurotrophic Factor Using HyStem^®-C Hydrogel Implants Improves Functional Recovery and Reduces Neuroinflammation in a Rat Model of Ischemic Stroke

Ischemic stroke is a leading cause of death and disability worldwide. Potential therapeutics aimed at neural repair and functional recovery are limited in their blood-brain barrier permeability and may exert systemic or off-target effects. We examined the effects of brain-derived neurotrophic factor (BDNF), delivered via an extended release HyStem®-C hydrogel implant or vehicle, on sensorimotor function, infarct volume, and neuroinflammation, following permanent distal middle cerebral artery occlusion (dMCAo) in rats. Eight days following dMCAo or sham surgery, treatments were implanted directly into the infarction site. Rats received either vehicle, BDNF-only (0.167 µg/µL), hydrogel-only, hydrogel impregnated with 0.057 µg/µL of BDNF (hydrogel + BDNFLOW), or hydrogel impregnated with 0.167 µg/µL of BDNF (hydrogel + BDNFHIGH). The adhesive removal test (ART) and 28-point Neuroscore (28-PN) were used to evaluate sensorimotor function up to two months post-ischemia. The hydrogel + BDNFHIGH group showed significant improvements on the ART six to eight weeks following treatment and their behavioral performance was consistently greater on the 28-PN. Infarct volume was reduced in rats treated with hydrogel + BDNFHIGH as were levels of microglial, phagocyte, and astrocyte marker immunoexpression in the corpus striatum. These data suggest that targeted intracerebral delivery of BDNF using hydrogels may mitigate ischemic brain injury and restore functional deficits by reducing neuroinflammation

Quantitative comparison of the IHC results between the gray and the white matter.

<p>(A) Distribution of HHV-6 positive glial cells in the encephalopathy group. (B) Distribution of S100 positive glial cells in the encephalopathy group. (C) Distribution of CD68 positive activated microglial cells/macrophages in the encephalopathy group and both control groups.</p

Quantitative comparison of the IHC results between PCR⁺ and PCR^- cases.

<p>(A) Distribution of HHV-6 positive astrocytes and oligodendrocytes in the white matter of the encephalopathy group. (B) Distribution of HHV-6 positive oligodendrocytes in the white matter of the encephalopathy group compared to controls.</p

Cellular localization of S100 antigen in the olfactory pathways.

<p>Cellular localization of S100 antigen in the olfactory pathways.</p

Prevalence of the CD68 positive activated microglial cells/macrophages.

<p>Prevalence of the CD68 positive activated microglial cells/macrophages.</p

IHC.

<p>(A) Immunoreactivity observed in the olfactory tract of HHV-6 positive subjects: HHV-6 immunopositivity in the astrocytes (white arrow) and oligodendrocytes (black arrow), × 250. Confocal microscopy, representative image of HHV-6, insert, × 1000. (B) S100 immunopositivity in the cells of the olfactory bulb: positive neurons (white arrows), negative neurons (arrowheads), astrocytes (black arrows), × 200. (C) S100 and GFAP immunopositivity in the astrocytes (white arrows) and S100 positive oligodendrocytes (black arrows) of the olfactory tract, × 250; insert, × 200. (D) CD68 immunopositivity in the activated microglial cells/macrophages close to the neurons (black arrows) and oligodendrocytes (white arrow) of the olfactory bulb, × 200. (E) CD68 immunopositivity in the activated microglial cells/macrophages (black arrows) and MBP expression (white arrows) of the olfactory tract, × 250; insert, × 100.</p