Immunohistochemical Localization of Erythropoietin and Its Receptor in the Developing Human Brain

1999 ◽  
Vol 2 (2) ◽  
pp. 148-158 ◽  
Author(s):  
Sandra E. Juul ◽  
Anthony T. Yachnis ◽  
Amyn M. Rojiani ◽  
Robert D. Christensen
Keyword(s):  
Human Brain ◽  
Ventricular Zone ◽  
Immunohistochemical Localization ◽  
Surgical Removal ◽  
Term Infants ◽  
Neuron Populations ◽  
Specific Distribution ◽  
Germinal Zone ◽  
Subventricular Zones ◽  
Human Brains

We have previously shown erythropoietin (Epo) and its receptor (Epo-R) to be present in the fetal human central nervous system (CNS), and Epo to be present in the spinal fluid of normal preterm and term infants. To investigate the cellular specificities and developmental patterns of expression of these polypeptides in the human brain—areas that have not been well researched—we designed the following study. Human brains ranging in maturity from 5 weeks post-conception to adult were preserved at the time of elective abortion, surgical removal (tubal pregnancy, or removal for temporal lobe epilepsy), or autopsy. Immunohistochemistry was used to localize Epo and Epo-R reactivity in brains of different stages of development. Astrocytes, neurons, and microglia were identified in sequential tissue sections by specific antibodies. At 5 to 6 weeks post-conception, both Epo and Epo-R localized to cells in the periventricular germinal zone. At 10 weeks post-conception, Epo immunoreactivity was present throughout the cortical wall, with the most intense immunoreactivity present in the ventricular and subventricular zones. Epo-R, in contrast, was localized primarily to the subventricular zone, with little staining evident in the ventricular zone. In late fetal brains, Epo-R reactivity was most prominent in astrocytic cells, although modest reactivity was observed in certain neuron populations. In contrast, Epo staining localized primarily to neurons in fetal brains, although a subpopulation of astrocytes was also immunoreactive. In postnatal brains, both astrocyte and neuron populations were immunoreactive with antibodies to Epo-R and Epo. From these results it is clear that Epo and its receptor are present in the developing human brain as early as 5 weeks post-conception, and each protein shows a specific distribution that changes with development. We speculate that Epo is important in neurodevelopment, and that it also plays a role in brain homeostasis later in life, functioning in an autocrine or paracrine manner.

scholarly journals Cellular resolution anatomical and molecular atlases for prenatal human brains

2021 ◽  
Author(s):  
Song-Lin Ding ◽  
Joshua J. Royall ◽  
Phil Lesnar ◽  
Benjamin A.C. Facer ◽  
Kimberly A. Smith ◽  
...  
Keyword(s):  
Human Brain ◽  
Hippocampal Formation ◽  
Marker Gene ◽  
Brain Structures ◽  
Marker Genes ◽  
Subcortical Structures ◽  
Cellular Resolution ◽  
Reliable Marker ◽  
Human Brains ◽  
Developmental Features

Increasing interest in studies of prenatal human brain development, particularly using new single-cell genomics and anatomical technologies to create cell atlases, creates a strong need for accurate and detailed anatomical reference atlases. In this study, we present two cellular-resolution digital anatomical atlases for prenatal human brain at post-conceptional weeks (PCW) 15 and 21. Both atlases were annotated on sequential Nissl-stained sections covering brain-wide structures on the basis of combined analysis of cytoarchitecture, acetylcholinesterase staining and an extensive marker gene expression dataset. This high information content dataset allowed reliable and accurate demarcation of developing cortical and subcortical structures and their subdivisions. Furthermore, using the anatomical atlases as a guide, spatial expression of 37 and 5 genes from the brains respectively at PCW 15 and 21 was annotated, illustrating reliable marker genes for many developing brain structures. Finally, the present study uncovered several novel developmental features, such as the lack of an outer subventricular zone in the hippocampal formation and entorhinal cortex, and the apparent extension of both cortical (excitatory) and subcortical (inhibitory) progenitors into the prenatal olfactory bulb. These comprehensive atlases provide useful tools for visualization, targeting, imaging and interpretation of brain structures of prenatal human brain, and for guiding and interpreting the next generation of cell census and connectome studies.

A singularity of PDGF alpha-receptor expression in the dorsoventral axis of the neural tube may define the origin of the oligodendrocyte lineage

Development ◽  
1993 ◽  
Vol 117 (2) ◽  
pp. 525-533 ◽  
Author(s):  
N.P. Pringle ◽  
W.D. Richardson
Keyword(s):  
Spinal Cord ◽  
Cell Fate ◽  
Neural Tube ◽  
Ventricular Zone ◽  
Central Canal ◽  
Receptor Expression ◽  
Foramen Of Monro ◽  
Dorsoventral Axis ◽  
Germinal Zone ◽  
Restricted Region

During rat embryogenesis, PDGF alpha receptor (PDGF-alpha R) mRNA is expressed in the ventral half of the spinal cord in two longitudinal columns, one each side of the central canal. Initially, these columns are only two cells wide but the cells subsequently appear to proliferate and disseminate throughout the spinal cord. Our previous studies of PDGF-alpha R expression in the developing CNS suggested that PDGF-alpha R may be a useful marker of the oligodendrocyte lineage in situ. The data presented here complement those studies and lead us to propose that the earliest oligodendrocyte precursors in the spinal cord originate in a very restricted region of the ventricular zone during a brief window of time around embryonic day 14 (E14). In the embryonic brain, migrating PDGF-alpha R+ cells appear to originate in a localized germinal zone in the ventral diencephalon (beneath the foramen of Monro). Our data demonstrate that gene expression and cell fate can be regulated with exquisite spatial resolution along the dorsoventral axis of the mammalian neural tube.

A human brain test bed for research in large vessel occlusion stroke

2021 ◽  
pp. 1-9
Author(s):  
Daniel Gebrezgiabhier ◽  
Yang Liu ◽  
Adithya S. Reddy ◽  
Evan Davis ◽  
Yihao Zheng ◽  
...  
Keyword(s):  
Human Brain ◽  
Mechanical Thrombectomy ◽  
Posterior Circulation ◽  
Large Vessel ◽  
Suction Catheter ◽  
Large Vessel Occlusion ◽  
Test Bed ◽  
Anterior Circulation ◽  
Vessel Occlusion ◽  
Human Brains

OBJECTIVEEndovascular removal of emboli causing large vessel occlusion (LVO)–related stroke utilizing suction catheter and/or stent retriever technologies or thrombectomy is a new standard of care. Despite high recanalization rates, 40% of stroke patients still experience poor neurological outcomes as many cases cannot be fully reopened after the first attempt. The development of new endovascular technologies and techniques for mechanical thrombectomy requires more sophisticated testing platforms that overcome the limitations of phantom-based simulators. The authors investigated the use of a hybrid platform for LVO stroke constructed with cadaveric human brains.METHODSA test bed for embolic occlusion of cerebrovascular arteries and mechanical thrombectomy was developed with cadaveric human brains, a customized hydraulic system to generate physiological flow rate and pressure, and three types of embolus analogs (elastic, stiff, and fragment-prone) engineered to match mechanically and phenotypically the emboli causing LVO strokes. LVO cases were replicated in the anterior and posterior circulation, and thrombectomy was attempted using suction catheters and/or stent retrievers.RESULTSThe test bed allowed radiation-free visualization of thrombectomy for LVO stroke in real cerebrovascular anatomy and flow conditions by transmural visualization of the intraluminal elements and procedures. The authors were able to successfully replicate 105 LVO cases with 184 passes in 12 brains (51 LVO cases and 82 passes in the anterior circulation, and 54 LVO cases and 102 passes in the posterior circulation). Observed recanalization rates in this model were graded using a Recanalization in LVO (RELVO) scale analogous to other measures of recanalization outcomes in clinical use.CONCLUSIONSThe human brain platform introduced and validated here enables the analysis of artery-embolus-device interaction under physiological hemodynamic conditions within the unmodified complexity of the cerebral vasculature inside the human brain.

Neo-Symbiosis

2011 ◽  
pp. 2773-2777
Author(s):  
Douglas Griffith ◽  
Frank L. Greitzer
Keyword(s):  
Human Factors ◽  
Human Brain ◽  
Computer Science ◽  
Information Science ◽  
Science And Technology ◽  
Historical Context ◽  
Process Data ◽  
Half Century ◽  
Human Brains ◽  
Computing Machines

The purpose of this article is to re-address the vision of human- computer symbiosis expressed by J. C. R. Licklider nearly a half century ago, when he wrote: “The hope is that in not too many years, human brains and computing machines will be coupled together very tightly, and that the resulting partnership will think as no human brain has ever thought and process data in a way not approached by the information- handling machines we know today” (Licklider, 1960). Unfortunately, little progress was made toward this vision over 4 decades following Licklider’s challenge, despite significant advancements in the fields of human factors and computer science. Licklider’s vision was largely forgotten. However, recent advances in information science and technology, psychology, and neuroscience have rekindled the potential of making the Licklider’s vision a reality. This article provides a historical context for and updates the vision, and it argues that such a vision is needed as a unifying framework for advancing IS&T.

Mental illness: The collision of meaning with mechanism

2020 ◽  
pp. 263-289
Author(s):  
Steven E. Hyman ◽  
Doug McConnell
Keyword(s):  
Mental Illness ◽  
Gene Regulation ◽  
Human Brain ◽  
Lived Experience ◽  
Clinical Encounter ◽  
Structure And Function ◽  
Human Beings ◽  
And Function ◽  
Human Brains ◽  
The Brain

‘Mental illness: the collision of meaning with mechanism’ is based on the views of psychiatry that Steven Hyman articulated in his Loebel Lectures—mental illness results from the disordered functioning of the human brain and effective treatment repairs or mitigates those malfunctions. This view is not intended as reductionist as causes of mental illness and contributions to their repair may come from any source that affects the structure and function of the brain. These might include social interactions and other sources of lived experience, ideas (such as those learned in cognitive therapy), gene sequences and gene regulation, metabolic factors, drugs, electrodes, and so on. This, however, is not the whole story for psychiatry on Hyman’s view; interpersonal interactions between clinicians and patients, intuitively understood in such folk psychological terms as selfhood, intention, and agency are also critical for successful practice. As human beings who are suffering, patients seek to make sense of their lives and benefit from the empathy, respect, and a sense of being understood not only as the objects of a clinical encounter, but also as subjects. Hyman’s argument, however, is that the mechanisms by which human brains function and malfunction to produce the symptoms and impairments of mental illness are opaque to introspection and that the mechanistic understandings necessary for diagnosis and treatment are incommensurate with intuitive (folk psychological) human self-understanding. Thus, psychiatry does best when skillful clinicians switch between an objectifying medical and neurobiological stance and the interpersonal stance in which the clinician engages the patients as a subject. Attempts to integrate these incommensurate views of patients and their predicaments have historically produced incoherent explanations of psychopathology and have often led treatment astray. For example, privileging of folk psychological testimony, even when filtered through sophisticated theories has historically led psychiatry into intellectually blind and clinically ineffective cul-de-sacs such as psychoanalysis.

scholarly journals Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography

2011 ◽  
Vol 31 (8) ◽  
pp. 1807-1816 ◽  
Author(s):  
Pablo M Rusjan ◽  
Alan A Wilson ◽  
Peter M Bloomfield ◽  
Irina Vitcu ◽  
Jeffrey H Meyer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Specific Binding ◽  
Compartment Model ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Specific Distribution ◽  
Positron Emission

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of VT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

Modeling the dose distribution in a human brain structure using CT images on the surface of Mars

2020 ◽  
Author(s):  
Salman Khaksarighiri ◽  
Jingnan Guo ◽  
Robert Wimmer-Schweingruber ◽  
Lennart Rostl
Keyword(s):  
Radiation Dose ◽  
Human Brain ◽  
Brain Structure ◽  
Dose Distribution ◽  
Cosmic Radiation ◽  
Cosmic Ray ◽  
Ct Images ◽  
Human Brains ◽  
The Impact ◽  
The Brain

&lt;p&gt;One of the most important steps in the near-future space age will be a manned mission to Mars. Unfortunately, such a mission will cause astronauts to be exposed to unavoidable cosmic radiation in deep space and on the surface of Mars. Thus a better understanding of the radiation environment for a Mars mission and the consequent biological impacts on humans, in particular the human brains, is critical. To investigate the impact of cosmic radiation on human brains and the potential influence on the brain functions, we model and study the cosmic particle-induced radiation dose in a realistic head structure. Specifically speaking, 134 slices of computed tomography (CT) images of an actual human head have been used as a 3D phantom in Geant4 (GEometry ANd Tracking) which is a Monte Carlo tool simulating energetic particles impinging into different parts of the brain and deliver radiation dose therein. As a first step, we compare the influence of different brain structures (e.g., with or without bones, with or without soft tissues) to the resulting dose therein to demonstrate the necessity of using a realistic brain structure for our investigation. Afterwards, we calculate energy-dependent functions of dose distribution for the most important (most abundant and most biologically-relevant) particle types encountered in space and on Mars such as protons, Helium ions and neutrons. These functions are then used to fold with Galactic Cosmic Ray (GCR) spectra on the surface of Mars for obtaining the dose rate distribution at different lobes of the human brain. Different GCR spectra during various solar cycle conditions have also been studied and compared.&lt;/p&gt;

Immunohistochemical Localization of a Dopamine Releasing Protein in Human Brain

1994 ◽  
Vol 7 (2) ◽  
pp. 171
Author(s):  
Ki Young Shin ◽  
Sang Do Bae ◽  
Jung Joong Kim ◽  
Seong Man Nau ◽  
Myeong Ok Kim ◽  
...  
Keyword(s):  
Human Brain ◽  
Immunohistochemical Localization
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