Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig.

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Dyson, Rebecca M; Palliser, Hannah K; Lakkundi, Anil; de Waal, Koert; Latter, Joanna L; Clifton, Vicki L; Wright, Ian M R

2014-09-17

Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion-reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29-36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68-71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion-reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period. © 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

The brain microvascular endothelium supports T cell proliferation and has potential for alloantigen presentation.

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Julie Wheway

Full Text Available Endothelial cells (EC form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4(+ and CD8(+ T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases.

Brain microvascular pericytes are immunoactive in culture: cytokine, chemokine, nitric oxide, and LRP-1 expression in response to lipopolysaccharide

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Erickson Michelle A

2011-10-01

Full Text Available Abstract Background Brain microvascular pericytes are important constituents of the neurovascular unit. These cells are physically the closest cells to the microvascular endothelial cells in brain capillaries. They significantly contribute to the induction and maintenance of the barrier functions of the blood-brain barrier. However, very little is known about their immune activities or their roles in neuroinflammation. Here, we focused on the immunological profile of brain pericytes in culture in the quiescent and immune-challenged state by studying their production of immune mediators such as nitric oxide (NO, cytokines, and chemokines. We also examined the effects of immune challenge on pericyte expression of low density lipoprotein receptor-related protein-1 (LRP-1, a protein involved in the processing of amyloid precursor protein and the brain-to-blood efflux of amyloid-β peptide. Methods Supernatants were collected from primary cultures of mouse brain pericytes. Release of nitric oxide (NO was measured by the Griess reaction and the level of S-nitrosylation of pericyte proteins measured with a modified "biotin-switch" method. Specific mitogen-activated protein kinase (MAPK pathway inhibitors were used to determine involvement of these pathways on NO production. Cytokines and chemokines were analyzed by multianalyte technology. The expression of both subunits of LRP-1 was analyzed by western blot. Results Lipopolysaccharide (LPS induced release of NO by pericytes in a dose-dependent manner that was mediated through MAPK pathways. Nitrative stress resulted in S-nitrosylation of cellular proteins. Eighteen of twenty-three cytokines measured were released constitutively by pericytes or with stimulation by LPS, including interleukin (IL-12, IL-13, IL-9, IL-10, granulocyte-colony stimulating factor, granulocyte macrophage-colony stimulating factor, eotaxin, chemokine (C-C motif ligand (CCL-3, and CCL-4. Pericyte expressions of both subunits of

Transcriptome of E. coli K1 bound to human brain microvascular endothelial cells

OpenAIRE

Xie, Yi; Parthasarathy, Geetha; Di Cello, Francescopaolo; Teng, Ching-Hao; Paul-Satyaseela, Maneesh; Kim, Kwang Sik

2007-01-01

Escherichia coli K1 is the most common Gram-negative organism causing neonatal meningitis. Binding to human brain microvascdular endothelial cells (HBMEC) is an essential step for E. coli K1 traversal of the blood-brain barrier. In this study, we examined expression profiles of E. coli K1 strain RS218 during its binding to HBMEC. Comparison of HBMEC-bound E. coli K1 with collagen-bound E. coli revealed more than one hundred genes whose expression patterns were significantly changed in HBMEC-b...

Blood-based biomarkers of microvascular pathology in Alzheimer's disease.

LENUS (Irish Health Repository)

Ewers, Michael

2012-02-01

Sporadic Alzheimer\\'s disease (AD) is a genetically complex and chronically progressive neurodegenerative disorder with molecular mechanisms and neuropathologies centering around the amyloidogenic pathway, hyperphosphorylation and aggregation of tau protein, and neurofibrillary degeneration. While cerebrovascular changes have not been traditionally considered to be a central part of AD pathology, a growing body of evidence demonstrates that they may, in fact, be a characteristic feature of the AD brain as well. In particular, microvascular abnormalities within the brain have been associated with pathological AD hallmarks and may precede neurodegeneration. In vivo assessment of microvascular pathology provides a promising approach to develop useful biological markers for early detection and pathological characterization of AD. This review focuses on established blood-based biological marker candidates of microvascular pathology in AD. These candidates include plasma concentration of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) that are increased in AD. Measures of endothelial vasodilatory function including endothelin (ET-1), adrenomedullin (ADM), and atrial natriuretic peptide (ANP), as well as sphingolipids are significantly altered in mild AD or during the predementia stage of mild cognitive impairment (MCI), suggesting sensitivity of these biomarkers for early detection and diagnosis. In conclusion, the emerging clinical diagnostic evidence for the value of blood-based microvascular biomarkers in AD is promising, however, still requires validation in phase II and III diagnostic trials. Moreover, it is still unclear whether the described protein dysbalances are early or downstream pathological events and how the detected systemic microvascular alterations relate to cerebrovascular and neuronal pathologies in the AD brain.

Edaravone Protected Human Brain Microvascular Endothelial Cells from Methylglyoxal-Induced Injury by Inhibiting AGEs/RAGE/Oxidative Stress

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Li, Wenlu; Xu, Hongjiao; Hu, Yangmin; He, Ping; Ni, Zhenzhen; Xu, Huimin; Zhang, Zhongmiao; Dai, Haibin

2013-01-01

Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10–100 µmol/l. What’s more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress. PMID:24098758

Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress.

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Wenlu Li

Full Text Available Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC, protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT formation, cell account, lactate dehydrogenase (LDH release and Rhodamine 123 staining. Advanced glycation end-products (AGEs formation and receptor for advanced glycation end-products (RAGE expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10-100 µmol/l. What's more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.

2-Chlorohexadecanoic acid induces ER stress and mitochondrial dysfunction in brain microvascular endothelial cells

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Eva Bernhart

2018-05-01

Full Text Available Peripheral leukocytes induce blood-brain barrier (BBB dysfunction through the release of cytotoxic mediators. These include hypochlorous acid (HOCl that is formed via the myeloperoxidase-H2O2-chloride system of activated phagocytes. HOCl targets the endogenous pool of ether phospholipids (plasmalogens generating chlorinated inflammatory mediators like e.g. 2-chlorohexadecanal and its conversion product 2-chlorohexadecanoic acid (2-ClHA. In the cerebrovasculature these compounds inflict damage to brain microvascular endothelial cells (BMVEC that form the morphological basis of the BBB. To follow subcellular trafficking of 2-ClHA we synthesized a ‘clickable’ alkyne derivative (2-ClHyA that phenocopied the biological activity of the parent compound. Confocal and superresolution structured illumination microscopy revealed accumulation of 2-ClHyA in the endoplasmic reticulum (ER and mitochondria of human BMVEC (hCMEC/D3 cell line. 2-ClHA and its alkyne analogue interfered with protein palmitoylation, induced ER-stress markers, reduced the ER ATP content, and activated transcription and secretion of interleukin (IL−6 as well as IL-8. 2-ClHA disrupted the mitochondrial membrane potential and induced procaspase-3 and PARP cleavage. The protein kinase R-like ER kinase (PERK inhibitor GSK2606414 suppressed 2-ClHA-mediated activating transcription factor 4 synthesis and IL-6/8 secretion, but showed no effect on endothelial barrier dysfunction and cleavage of procaspase-3. Our data indicate that 2-ClHA induces potent lipotoxic responses in brain endothelial cells and could have implications in inflammation-induced BBB dysfunction.

Blood-brain barrier dysfunction and amyloid precursor protein accumulation in microvascular compartment following ischemia-reperfusion brain injury with 1-year survival.

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Pluta, R

2003-01-01

This study examined the late microvascular consequences of brain ischemia due to cardiac arrest in rats. In reacted vibratome sections scattered foci of extravasated horseradish peroxidase were noted throughout the brain and did not appear to be restricted to any specific area of brain. Ultrastructural investigation of leaky sites frequently presented platelets adhering to the endothelium of venules and capillaries. Endothelial cells demonstrated pathological changes with evidence of perivascular astrocytic swelling. At the same time, we noted C-terminal of amyloid precursor protein/beta-amyloid peptide (CAPP/betaA) deposits in cerebral blood vessels, with a halo of CAPP/betaA immunoreactivity in the surrounding parenchyma suggested diffusion of CAPP/betaA out of the vascular compartment. Changes predominated in the hippocampus, cerebral and entorhinal cortex, corpus callosum, thalamus, basal ganglia and around the lateral ventricles. These data implicate delayed abnormal endothelial function of vessels following ischemia-reperfusion brain injury as a primary event in the pathogenesis of the recurrent cerebral infarction.

Ghrelin stimulates angiogenesis in human microvascular endothelial cells: Implications beyond GH release

International Nuclear Information System (INIS)

Li Aihua; Cheng Guangli; Zhu Genghui; Tarnawski, Andrzej S.

2007-01-01

Ghrelin, a peptide hormone isolated from the stomach, releases growth hormone and stimulates appetite. Ghrelin is also expressed in pancreas, kidneys, cardiovascular system and in endothelial cells. The precise role of ghrelin in endothelial cell functions remains unknown. We examined the expression of ghrelin and its receptor (GHSR1) mRNAs and proteins in human microvascular endothelial cells (HMVEC) and determined whether ghrelin affects in these cells proliferation, migration and in vitro angiogenesis; and whether MAPK/ERK2 signaling is important for the latter action. We found that ghrelin and GHSR1 are constitutively expressed in HMVEC. Treatment of HMVEC with exogenous ghrelin significantly increased in these cells proliferation, migration, in vitro angiogenesis and ERK2 phosphorylation. MEK/ERK2 inhibitor, PD 98059 abolished ghrelin-induced in vitro angiogenesis. This is First demonstration that ghrelin and its receptor are expressed in human microvascular endothelial cells and that ghrelin stimulates HMVEC proliferation, migration, and angiogenesis through activation of ERK2 signaling

Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

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Musolino, Patricia L; Gong, Yi; Snyder, Juliet M T; Jimenez, Sandra; Lok, Josephine; Lo, Eng H; Moser, Ann B; Grabowski, Eric F; Frosch, Matthew P; Eichler, Florian S

2015-11-01

See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage

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Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf

2015-01-01

, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. METHODS: In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface...

Microvascular Recruitment in Insulin Resistance

DEFF Research Database (Denmark)

Sjøberg, Kim Anker

the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...... hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...

Glial cell ceruloplasmin and hepcidin differentially regulate iron efflux from brain microvascular endothelial cells.

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McCarthy, Ryan C; Kosman, Daniel J

2014-01-01

We have used an in vitro model system to probe the iron transport pathway across the brain microvascular endothelial cells (BMVEC) of the blood-brain barrier (BBB). This model consists of human BMVEC (hBMVEC) and C6 glioma cells (as an astrocytic cell line) grown in a transwell, a cell culture system commonly used to quantify metabolite flux across a cell-derived barrier. We found that iron efflux from hBMVEC through the ferrous iron permease ferroportin (Fpn) was stimulated by secretion of the soluble form of the multi-copper ferroxidase, ceruloplasmin (sCp) from the co-cultured C6 cells. Reciprocally, expression of sCp mRNA in the C6 cells was increased by neighboring hBMVEC. In addition, data indicate that C6 cell-secreted hepcidin stimulates internalization of hBMVEC Fpn but only when the end-feet projections characteristic of this glia-derived cell line are proximal to the endothelial cells. This hepcidin-dependent loss of Fpn correlated with knock-down of iron efflux from the hBMVEC; this result was consistent with the mechanism by which hepcidin regulates iron efflux in mammalian cells. In summary, the data support a model of iron trafficking across the BBB in which the capillary endothelium induce the underlying astrocytes to produce the ferroxidase activity needed to support Fpn-mediated iron efflux. Reciprocally, astrocyte proximity modulates the effective concentration of hepcidin at the endothelial cell membrane and thus the surface expression of hBMVEC Fpn. These results are independent of the source of hBMVEC iron (transferrin or non-transferrin bound) indicating that the model developed here is broadly applicable to brain iron homeostasis.

In vitro analysis of human periodontal microvascular endothelial cells.

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Tsubokawa, Mizuki; Sato, Soh

2014-08-01

Endothelial cells (ECs) participate in key aspects of vascular biology, such as maintenance of capillary permeability, initiation of coagulation, and regulation of inflammation. According to previous reports, ECs have revealed highly specific characteristics depending on the organs and tissues. However, some reports have described the characteristics of the capillaries formed by human periodontal ECs. Therefore, the aim of the present study is to examine the functional characteristics of the periodontal microvascular ECs in vitro. Human periodontal ligament-endothelial cells (HPDL-ECs) and human gingiva-endothelial cells (HG-ECs) were isolated by immunoprecipitation with magnetic beads conjugated to a monoclonal anti-CD31 antibody. The isolated HPDL-ECs and HG-ECs were characterized to definitively demonstrate that these cell cultures represented pure ECs. Human umbilical-vein ECs and human dermal microvascular ECs were used for comparison. These cells were compared according to the proliferation potential, the formation of capillary-like tubes, the transendothelial electric resistance (TEER), and the expression of tight junction proteins. HPDL-ECs and HG-ECs with characteristic cobblestone monolayer morphology were obtained, as determined by light microscopy at confluence. Furthermore, the HPDL-ECs and HG-ECs expressed the EC markers platelet endothelial cell adhesion molecule-1 (also known as CD31), von Willebrand factor, and Ulex europaeus agglutinin 1, and the cells stained strongly positive for CD31 and CD309. In addition, the HPDL-ECs and HG-ECs were observed to form capillary-like tubes, and they demonstrated uptake of acetylated low-density lipoprotein. Functional analyses of the HPDL-ECs and HG-ECs showed that, compared to the control cells, tube formation persisted for only a brief period of time, and TEER was substantially reduced at confluence. Furthermore, the cells exhibited delocalization of zonula occludens-1 and occludin at cell-cell contact sites

High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature.

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Li, Wei; Maloney, Ronald E; Aw, Tak Yee

2015-08-01

We previously demonstrated that in normal glucose (5mM), methylglyoxal (MG, a model of carbonyl stress) induced brain microvascular endothelial cell (IHEC) dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC). Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER) was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia); moreover, barrier function remained disrupted 6h after cell transfer to normal glucose media (acute glycemic fluctuation). Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH) synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal) levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG-occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG-occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

High glucose, glucose fluctuation and carbonyl stress enhance brain microvascular endothelial barrier dysfunction: Implications for diabetic cerebral microvasculature

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Wei Li

2015-08-01

Full Text Available We previously demonstrated that in normal glucose (5 mM, methylglyoxal (MG, a model of carbonyl stress induced brain microvascular endothelial cell (IHEC dysfunction that was associated with occludin glycation and prevented by N-acetylcysteine (NAC. Herein, we investigated the impact of high glucose and low GSH, conditions that mimicked the diabetic state, on MG-induced IHEC dysfunction. MG-induced loss of transendothelial electrical resistance (TEER was potentiated in IHECs cultured for 7 or 12 days in 25 mM glucose (hyperglycemia; moreover, barrier function remained disrupted 6 h after cell transfer to normal glucose media (acute glycemic fluctuation. Notably, basal occludin glycation was elevated under these glycemic states. TEER loss was exaggerated by inhibition of glutathione (GSH synthesis and abrogated by NAC, which corresponded to GSH decreases and increases, respectively. Significantly, glyoxalase II activity was attenuated in hyperglycemic cells. Moreover, hyperglycemia and GSH inhibition increased MG accumulation, consistent with a compromised capacity for MG elimination. α-Oxoaldehydes (MG plus glyoxal levels were elevated in streptozotocin-induced diabetic rat plasma. Immunohistochemistry revealed a prevalence of MG-positive, but fewer occludin-positive microvessels in the diabetic brain in vivo, and Western analysis confirmed an increase in MG–occludin adducts. These results provide the first evidence that hyperglycemia and acute glucose fluctuation promote MG–occludin formation and exacerbate brain microvascular endothelial dysfunction. Low occludin expression and high glycated-occludin contents in diabetic brain in vivo are factors that would contribute to the dysfunction of the cerebral microvasculature during diabetes.

Adhesive properties of Enterobacter sakazakii to human epithelial and brain microvascular endothelial cells

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Pospischil Andreas

2006-06-01

Full Text Available Abstract Background Enterobacter sakazakii is an opportunistic pathogen that has been associated with sporadic cases and outbreaks causing meningitis, necrotizing enterocolitis and sepsis especially in neonates. However, up to now little is known about the mechanisms of pathogenicity in E. sakazakii. A necessary state in the successful colonization, establishment and ultimately production of disease by microbial pathogens is the ability to adhere to host surfaces such as mucous membranes, gastric and intestinal epithelial or endothelial tissue. This study examined for the first time the adherence ability of 50 E. sakazakii strains to the two epithelial cell lines HEp-2 and Caco-2, as well as the brain microvascular endothelial cell line HBMEC. Furthermore, the effects of bacterial culture conditions on the adherence behaviour were investigated. An attempt was made to characterize the factors involved in adherence. Results Two distinctive adherence patterns, a diffuse adhesion and the formation of localized clusters of bacteria on the cell surface could be distinguished on all three cell lines. In some strains, a mixture of both patterns was observed. Adherence was maximal during late exponential phase, and increased with higher MOI. The adhesion capacity of E. sakazakii to HBMEC cells was affected by the addition of blood to the bacteria growth medium. Mannose, hemagglutination, trypsin digestion experiments and transmission electron microscopy suggested that the adhesion of E. sakazakii to the epithelial and endothelial cells is mainly non-fimbrial based. Conclusion Adherence experiments show heterogeneity within different E. sakazakii strains. In agreement with studies on E. cloacae, we found no relationship between the adhesive capacities in E. sakazakii and the eventual production of specific fimbriae. Further studies will have to be carried out in order to determine the adhesin(s involved in the interaction of E. sakazakii with cells and to

GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

DEFF Research Database (Denmark)

Sjøberg, Kim Anker; Holst, Jens Juul; Rattigan, Stephen

2014-01-01

The insulinotropic gut hormone, glucagon-like-peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery...... in overnight fasted healthy young men. Microvascular recruitment was measured with real time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by co-infusion of octreotide. As a positive control, MVR and leg...

Comparative study of expression and activity of glucose transporters between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells.

Science.gov (United States)

Al-Ahmad, Abraham J

2017-10-01

Glucose constitutes a major source of energy of mammalian brains. Glucose uptake at the blood-brain barrier (BBB) occurs through a facilitated glucose transport, through glucose transporter 1 (GLUT1), although other isoforms have been described at the BBB. Mutations in GLUT1 are associated with the GLUT1 deficiency syndrome, yet none of the current in vitro models of the human BBB maybe suited for modeling such a disorder. In this study, we investigated the expression of glucose transporters and glucose diffusion across brain microvascular endothelial cells (BMECs) derived from healthy patient-derived induced pluripotent stem cells (iPSCs). We investigated the expression of different glucose transporters at the BBB using immunocytochemistry and flow cytometry and measured glucose uptake and diffusion across BMEC monolayers obtained from two iPSC lines and from hCMEC/D3 cells. BMEC monolayers showed expression of several glucose transporters, in particular GLUT1, GLUT3, and GLUT4. Diffusion of glucose across the monolayers was mediated via a saturable transcellular mechanism and partially inhibited by pharmacological inhibitors. Taken together, our study suggests the presence of several glucose transporters isoforms at the human BBB and demonstrates the feasibility of modeling glucose across the BBB using patient-derived stem cells. Copyright © 2017 the American Physiological Society.

Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study.

Science.gov (United States)

Kim, Dae Hyun; Grodstein, Francine; Newman, Anne B; Chaves, Paulo H M; Odden, Michelle C; Klein, Ronald; Sarnak, Mark J; Lipsitz, Lewis A

2015-09-01

To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function Cross-sectional analysis of the Cardiovascular Health Study (1998-1999). Community. Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5). Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand) Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function. Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication. © 2015, Copyright the Authors Journal compilation © 2015

Exposure to lipopolysaccharide and/or unconjugated bilirubin impair the integrity and function of brain microvascular endothelial cells.

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Filipa L Cardoso

Full Text Available BACKGROUND: Sepsis and jaundice are common conditions in newborns that can lead to brain damage. Though lipopolysaccharide (LPS is known to alter the integrity of the blood-brain barrier (BBB, little is known on the effects of unconjugated bilirubin (UCB and even less on the joint effects of UCB and LPS on brain microvascular endothelial cells (BMEC. METHODOLOGY/PRINCIPAL FINDINGS: Monolayers of primary rat BMEC were treated with 1 µg/ml LPS and/or 50 µM UCB, in the presence of 100 µM human serum albumin, for 4 or 24 h. Co-cultures of BMEC with astroglial cells, a more complex BBB model, were used in selected experiments. LPS led to apoptosis and UCB induced both apoptotic and necrotic-like cell death. LPS and UCB led to inhibition of P-glycoprotein and activation of matrix metalloproteinases-2 and -9 in mono-cultures. Transmission electron microscopy evidenced apoptotic bodies, as well as damaged mitochondria and rough endoplasmic reticulum in BMEC by either insult. Shorter cell contacts and increased caveolae-like invaginations were noticeable in LPS-treated cells and loss of intercellular junctions was observed upon treatment with UCB. Both compounds triggered impairment of endothelial permeability and transendothelial electrical resistance both in mono- and co-cultures. The functional changes were confirmed by alterations in immunostaining for junctional proteins β-catenin, ZO-1 and claudin-5. Enlargement of intercellular spaces, and redistribution of junctional proteins were found in BMEC after exposure to LPS and UCB. CONCLUSIONS: LPS and/or UCB exert direct toxic effects on BMEC, with distinct temporal profiles and mechanisms of action. Therefore, the impairment of brain endothelial integrity upon exposure to these neurotoxins may favor their access to the brain, thus increasing the risk of injury and requiring adequate clinical management of sepsis and jaundice in the neonatal period.

Reduced cortical microvascular oxygenation in multiple sclerosis: a blinded, case-controlled study using a novel quantitative near-infrared spectroscopy method

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Yang, Runze; Dunn, Jeff F.

2015-11-01

Hypoxia (low oxygen) is associated with many brain disorders as well as inflammation, but the lack of widely available technology has limited our ability to study hypoxia in human brain. Multiple sclerosis (MS) is a poorly understood neurological disease with a significant inflammatory component which may cause hypoxia. We hypothesized that if hypoxia were to occur, there should be reduced microvascular hemoglobin saturation (StO2). In this study, we aimed to determine if reduced StO2 can be detected in MS using frequency domain near-infrared spectroscopy (fdNIRS). We measured fdNIRS data in cortex and assessed disability of 3 clinical isolated syndrome (CIS), 72 MS patients and 12 controls. Control StO2 was 63.5 ± 3% (mean ± SD). In MS patients, 42% of StO2 values were more than 2 × SD lower than the control mean. There was a significant relationship between StO2 and clinical disability. A reduced microvascular StO2 is supportive (although not conclusive) that there may be hypoxic regions in MS brain. This is the first study showing how quantitative NIRS can be used to detect reduced StO2 in patients with MS, opening the door to understanding how microvascular oxygenation impacts neurological conditions.

Modeling of Cerebral Oxygen Transport Based on In vivo Microscopic Imaging of Microvascular Network Structure, Blood Flow, and Oxygenation.

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Gagnon, Louis; Smith, Amy F; Boas, David A; Devor, Anna; Secomb, Timothy W; Sakadžić, Sava

2016-01-01

Oxygen is delivered to brain tissue by a dense network of microvessels, which actively control cerebral blood flow (CBF) through vasodilation and contraction in response to changing levels of neural activity. Understanding these network-level processes is immediately relevant for (1) interpretation of functional Magnetic Resonance Imaging (fMRI) signals, and (2) investigation of neurological diseases in which a deterioration of neurovascular and neuro-metabolic physiology contributes to motor and cognitive decline. Experimental data on the structure, flow and oxygen levels of microvascular networks are needed, together with theoretical methods to integrate this information and predict physiologically relevant properties that are not directly measurable. Recent progress in optical imaging technologies for high-resolution in vivo measurement of the cerebral microvascular architecture, blood flow, and oxygenation enables construction of detailed computational models of cerebral hemodynamics and oxygen transport based on realistic three-dimensional microvascular networks. In this article, we review state-of-the-art optical microscopy technologies for quantitative in vivo imaging of cerebral microvascular structure, blood flow and oxygenation, and theoretical methods that utilize such data to generate spatially resolved models for blood flow and oxygen transport. These "bottom-up" models are essential for the understanding of the processes governing brain oxygenation in normal and disease states and for eventual translation of the lessons learned from animal studies to humans.

Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

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Alcendor Donald J

2012-05-01

Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

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Prisby, Rhonda D

2014-07-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (pnecrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone Marrow Blood Vessel Ossification and “Microvascular Dead Space” in Rat and Human Long Bone

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Prisby, Rhonda D.

2014-01-01

Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4–6 mon; n=8) and old (22–24 mon; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner’s Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via µCT to quantify microvascular ossification. Bone marrow blood vessels from rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and “normal” vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p necrosis. The progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the difficulties treating bone disease in the elderly. PMID:24680721

Renal microvascular disease in an aging population: a reversible process?

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Futrakul, Narisa; Futrakul, Prasit

2008-01-01

Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process.

MicroRNA Signature of Human Microvascular Endothelium Infected with Rickettsia rickettsii

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Abha Sahni

2017-07-01

Full Text Available MicroRNAs (miRNAs mediate gene silencing by destabilization and/or translational repression of target mRNA. Infection of human microvascular endothelial cells as primary targets of Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever, triggers host responses appertaining to alterations in cellular gene expression. Microarray-based profiling of endothelial cells infected with R. rickettsii for 3 or 24 h revealed differential expression of 33 miRNAs, of which miRNAs129-5p, 200a-3p, 297, 200b-3p, and 595 were identified as the top five up-regulated miRNAs (5 to 20-fold, p ≤ 0.01 and miRNAs 301b-3p, 548a-3p, and 377-3p were down-regulated (2 to 3-fold, p ≤ 0.01. Changes in the expression of selected miRNAs were confirmed by q-RT-PCR in both in vitro and in vivo models of infection. As potential targets, expression of genes encoding NOTCH1, SMAD2, SMAD3, RIN2, SOD1, and SOD2 was either positively or negatively regulated. Using a miRNA-specific mimic or inhibitor, NOTCH1 was determined to be a target of miRNA 200a-3p in R. rickettsii-infected human dermal microvascular endothelial cells (HMECs. Predictive interactome mapping suggested the potential for miRNA-mediated modulation of regulatory gene networks underlying important host cell signaling pathways. This first demonstration of altered endothelial miRNA expression provides new insights into regulatory elements governing mechanisms of host responses and pathogenesis during human rickettsial infections.

Microvascular Cranial Nerve Palsy

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... Español Eye Health / Eye Health A-Z Microvascular Cranial Nerve Palsy Sections What Is Microvascular Cranial Nerve Palsy? ... Microvascular Cranial Nerve Palsy Treatment What Is Microvascular Cranial Nerve Palsy? Leer en Español: ¿Qué es una parálisis ...

Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models.

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Eduard Urich

Full Text Available Brain microvascular endothelial cells (BEC constitute the blood-brain barrier (BBB which forms a dynamic interface between the blood and the central nervous system (CNS. This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local

Wide-area mapping of resting state hemodynamic correlations at microvascular resolution with multi-contrast optical imaging (Conference Presentation)

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Senarathna, Janaka; Hadjiabadi, Darian; Gil, Stacy; Thakor, Nitish V.; Pathak, Arvind P.

2017-02-01

Different brain regions exhibit complex information processing even at rest. Therefore, assessing temporal correlations between regions permits task-free visualization of their `resting state connectivity'. Although functional MRI (fMRI) is widely used for mapping resting state connectivity in the human brain, it is not well suited for `microvascular scale' imaging in rodents because of its limited spatial resolution. Moreover, co-registered cerebral blood flow (CBF) and total hemoglobin (HbT) data are often unavailable in conventional fMRI experiments. Therefore, we built a customized system that combines laser speckle contrast imaging (LSCI), intrinsic optical signal (IOS) imaging and fluorescence imaging (FI) to generate multi-contrast functional connectivity maps at a spatial resolution of 10 μm. This system comprised of three illumination sources: a 632 nm HeNe laser (for LSCI), a 570 nm ± 5 nm filtered white light source (for IOS), and a 473 nm blue laser (for FI), as well as a sensitive CCD camera operating at 10 frames per second for image acquisition. The acquired data enabled visualization of changes in resting state neurophysiology at microvascular spatial scales. Moreover, concurrent mapping of CBF and HbT-based temporal correlations enabled in vivo mapping of how resting brain regions were linked in terms of their hemodynamics. Additionally, we complemented this approach by exploiting the transit times of a fluorescent tracer (Dextran-FITC) to distinguish arterial from venous perfusion. Overall, we demonstrated the feasibility of wide area mapping of resting state connectivity at microvascular resolution and created a new toolbox for interrogating neurovascular function.

Microvascular Anastomosis Training in Neurosurgery: A Review

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Vadim A. Byvaltsev

2018-01-01

Full Text Available Cerebrovascular diseases are among the most widespread diseases in the world, which largely determine the structure of morbidity and mortality rates. Microvascular anastomosis techniques are important for revascularization surgeries on brachiocephalic and carotid arteries and complex cerebral aneurysms and even during resection of brain tumors that obstruct major cerebral arteries. Training in microvascular surgery became even more difficult with less case exposure and growth of the use of endovascular techniques. In this text we will briefly discuss the history of microvascular surgery, review current literature on simulation models with the emphasis on their merits and shortcomings, and describe the views and opinions on the future of the microvascular training in neurosurgery. In “dry” microsurgical training, various models created from artificial materials that simulate biological tissues are used. The next stage in training more experienced surgeons is to work with nonliving tissue models. Microvascular training using live models is considered to be the most relevant due to presence of the blood flow. Training on laboratory animals has high indicators of face and constructive validity. One of the future directions in the development of microsurgical techniques is the use of robotic systems. Robotic systems may play a role in teaching future generations of microsurgeons. Modern technologies allow access to highly accurate learning environments that are extremely similar to real environment. Additionally, assessment of microsurgical skills should become a fundamental part of the current evaluation of competence within a microneurosurgical training program. Such an assessment tool could be utilized to ensure a constant level of surgical competence within the recertification process. It is important that this evaluation be based on validated models.

Molecular anatomy of interendothelial junctions in human blood-brain barrier microvessels.

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Andrzej W Vorbrodt

2004-07-01

Full Text Available Immunogold cytochemical procedure was used to study the localization at the ultrastructural level of interendothelial junction-associated protein molecules in the human brain blood microvessels, representing the anatomic site of the blood-brain barrier (BBB. Ultrathin sections of Lowicryl K4M-embedded biopsy specimens of human cerebral cortex obtained during surgical procedures were exposed to specific antibodies, followed by colloidal gold-labeled secondary antibodies. All tight junction-specific integral membrane (transmembrane proteins--occludin, junctional adhesion molecule (JAM-1, and claudin-5--as well as peripheral zonula occludens protein (ZO-1 were highly expressed. Immunoreactivity of the adherens junction-specific transmembrane protein VE-cadherin was of almost similar intensity. Immunolabeling of the adherens junction-associated peripheral proteins--alpha-catenin, beta-catenin, and p120 catenin--although positive, was evidently less intense. The expression of gamma-catenin (plakoglobin was considered questionable because solitary immunosignals (gold particles appeared in only a few microvascular profiles. Double labeling of some sections made possible to observe strict colocalization of the junctional molecules, such as occludin and ZO-1 or JAM-1 and VE-cadherin, in the interendothelial junctions. We found that in human brain microvessels, the interendothelial junctional complexes contain molecular components specific for both tight and adherens junctions. It is assumed that the data obtained can help us find the immunodetectable junctional molecules that can serve as sensitive markers of normal or abnormal function of the BBB.

Early invasion of brain parenchyma by African trypanosomes.

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Ute Frevert

Full Text Available Human African trypanosomiasis or sleeping sickness is a vector-borne parasitic disease that has a major impact on human health and welfare in sub-Saharan countries. Based mostly on data from animal models, it is currently thought that trypanosome entry into the brain occurs by initial infection of the choroid plexus and the circumventricular organs followed days to weeks later by entry into the brain parenchyma. However, Trypanosoma brucei bloodstream forms rapidly cross human brain microvascular endothelial cells in vitro and appear to be able to enter the murine brain without inflicting cerebral injury. Using a murine model and intravital brain imaging, we show that bloodstream forms of T. b. brucei and T. b. rhodesiense enter the brain parenchyma within hours, before a significant level of microvascular inflammation is detectable. Extravascular bloodstream forms were viable as indicated by motility and cell division, and remained detectable for at least 3 days post infection suggesting the potential for parasite survival in the brain parenchyma. Vascular inflammation, as reflected by leukocyte recruitment and emigration from cortical microvessels, became apparent only with increasing parasitemia at later stages of the infection, but was not associated with neurological signs. Extravascular trypanosomes were predominantly associated with postcapillary venules suggesting that early brain infection occurs by parasite passage across the neuroimmunological blood brain barrier. Thus, trypanosomes can invade the murine brain parenchyma during the early stages of the disease before meningoencephalitis is fully established. Whether individual trypanosomes can act alone or require the interaction from a quorum of parasites remains to be shown. The significance of these findings for disease development is now testable.

Microvascular Endothelial Dysfunction in Sedentary, Obese Humans is mediated by NADPH Oxidase; Influence of Exercise Training

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La Favor, Justin D.; Dubis, Gabriel S.; Yan, Huimin; White, Joseph D.; Nelson, Margaret A.M.; Anderson, Ethan J.; Hickner, Robert C.

2016-01-01

Objective The objectives of this study were to determine the impact of in vivo reactive oxygen species (ROS) on microvascular endothelial function in obese human subjects and to determine the efficacy of an aerobic exercise intervention on alleviating obesity-associated dysfunctionality. Approach and Results Young, sedentary men and women were divided into lean (BMI 18–25; n=14), intermediate (BMI 28–32.5; n=13), and obese (BMI 33–40; n=15) groups. A novel microdialysis technique was utilized to detect elevated interstitial hydrogen peroxide (H2O2) and superoxide levels in the vastus lateralis of obese compared to both lean and intermediate subjects. Nutritive blood flow was monitored in the vastus lateralis via the microdialysis-ethanol technique. A decrement in acetylcholine-stimulated blood flow revealed impaired microvascular endothelial function in the obese subjects. Perfusion of apocynin, an NADPH oxidase (Nox) inhibitor, lowered (normalized) H2O2 and superoxide levels and reversed microvascular endothelial dysfunction in obese subjects. Following 8-weeks of exercise, H2O2 levels were decreased in the obese subjects and microvascular endothelial function in these subjects was restored to levels similar to lean subjects. Skeletal muscle protein expression of the Nox subunits p22phox, p47phox, and p67phox were increased in obese relative to lean subjects, where p22phox and p67phox expression was attenuated by exercise training in obese subjects. Conclusions This study implicates Nox as a source of excessive ROS production in skeletal muscle of obese individuals, and links excessive Nox derived ROS to microvascular endothelial dysfunction in obesity. Furthermore, aerobic exercise training proved to be an effective strategy for alleviating these maladies. PMID:27765769

Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium.

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Jackson, C J; Garbett, P K; Nissen, B; Schrieber, L

1990-06-01

A major problem encountered when isolating human microvascular endothelium is the presence of contaminating cells such as fibroblasts that rapidly over-grow the endothelial cells. We describe here a simple, rapid technique for purifying endothelial cells derived from the microvasculature of neonatal foreskin and osteoarthritic and rheumatoid arthritic synovium. This technique is based on the selective binding of the lectin Ulex europaeus I (UEA I) to the endothelial cell surface via fucose residues. Initially UEA I was covalently bound to tosyl-activated super-paramagnetic polystyrene beads (Dynabeads) by incubation for 24 h at room temperature. Cells were isolated by extracting microvascular segments from enzyme-treated (trypsin and Pronase) cubes of tissue. The mixed population of cells obtained were purified by incubating them at 4 degrees C for 10 min with the UEA I-coated Dynabeads. Endothelium bound to the beads whilst contaminating cells were removed by five washes with HBSS using a magnetic particle concentrator. The endothelial cells thus obtained grew to confluence as a cobblestone-like monolayer and expressed von Willebrand factor antigen. The cells were released from the Dynabeads by the competitive binding of fucose (10 min at 4 degrees C). This new method is simple and reproducible and allows pure human microvascular endothelial cells to be cultured within 2 h of obtaining a specimen.

ZO-1 expression is suppressed by GM-CSF via miR-96/ERG in brain microvascular endothelial cells.

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Zhang, Hu; Zhang, Shuhong; Zhang, Jilin; Liu, Dongxin; Wei, Jiayi; Fang, Wengang; Zhao, Weidong; Chen, Yuhua; Shang, Deshu

2018-05-01

The level of granulocyte-macrophage colony-stimulating factor (GM-CSF) increases in some disorders such as vascular dementia, Alzheimer's disease, and multiple sclerosis. We previously reported that in Alzheimer's disease patients, a high level of GM-CSF in the brain parenchyma downregulated expression of ZO-1, a blood-brain barrier tight junction protein, and facilitated the infiltration of peripheral monocytes across the blood-brain barrier. However, the molecular mechanism underlying regulation of ZO-1 expression by GM-CSF is unclear. Herein, we found that the erythroblast transformation-specific (ETS) transcription factor ERG cooperated with the proto-oncogene protein c-MYC in regulation of ZO-1 transcription in brain microvascular endothelial cells (BMECs). The ERG expression was suppressed by miR-96 which was increased by GM-CSF through the phosphoinositide-3 kinase (PI3K)/Akt pathway. Inhibition of miR-96 prevented ZO-1 down-regulation induced by GM-CSF both in vitro and in vivo. Our results revealed the mechanism of ZO-1 expression reduced by GM-CSF, and provided a potential target, miR-96, which could block ZO-1 down-regulation caused by GM-CSF in BMECs.

Agrin in Alzheimer's Disease: Altered Solubility and Abnormal Distribution within Microvasculature and Brain Parenchyma

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Donahue, John E.; Berzin, Tyler M.; Rafii, Michael S.; Glass, David J.; Yancopoulos, George D.; Fallon, Justin R.; Stopa, Edward G.

1999-05-01

Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with β -amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to β -amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.

Endothelial network formed with human dermal microvascular endothelial cells in autologous multicellular skin substitutes.

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Ponec, Maria; El Ghalbzouri, Abdoelwaheb; Dijkman, Remco; Kempenaar, Johanna; van der Pluijm, Gabri; Koolwijk, Pieter

2004-01-01

A human skin equivalent from a single skin biopsy harboring keratinocytes and melanocytes in the epidermal compartment, and fibroblasts and microvascular dermal endothelial cells in the dermal compartment was developed. The results of the study revealed that the nature of the extracellular matrix of the dermal compartments plays an important role in establishment of endothelial network in vitro. With rat-tail type I collagen matrices only lateral but not vertical expansion of endothelial networks was observed. In contrast, the presence of extracellular matrix of entirely human origin facilitated proper spatial organization of the endothelial network. Namely, when human dermal fibroblasts and microvascular endothelial cells were seeded on the bottom of an inert filter and subsequently epidermal cells were seeded on top of it, fibroblasts produced extracellular matrix throughout which numerous branched tubes were spreading three-dimensionally. Fibroblasts also facilitated the formation of basement membrane at the epidermal/matrix interface. Under all culture conditions, fully differentiated epidermis was formed with numerous melanocytes present in the basal epidermal cell layer. The results of the competitive RT-PCR revealed that both keratinocytes and fibroblasts expressed VEGF-A, -B, -C, aFGF and bFGF mRNA, whereas fibroblasts also expressed VEGF-D mRNA. At protein level, keratinocytes produced 10 times higher amounts of VEGF-A than fibroblasts did. The generation of multicellular skin equivalent from a single human skin biopsy will stimulate further developments for its application in the treatment of full-thickness skin defects. The potential development of biodegradable, biocompatible material suitable for these purposes is a great challenge for future research.

Characterization of TEM1/endosialin in human and murine brain tumors

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Carson-Walter, Eleanor B; Walter, Kevin A; Winans, Bethany N; Whiteman, Melissa C; Liu, Yang; Jarvela, Sally; Haapasalo, Hannu; Tyler, Betty M; Huso, David L; Johnson, Mahlon D

2009-01-01

TEM1/endosialin is an emerging microvascular marker of tumor angiogenesis. We characterized the expression pattern of TEM1/endosialin in astrocytic and metastatic brain tumors and investigated its role as a therapeutic target in human endothelial cells and mouse xenograft models. In situ hybridization (ISH), immunohistochemistry (IH) and immunofluorescence (IF) were used to localize TEM1/endosialin expression in grade II-IV astrocytomas and metastatic brain tumors on tissue microarrays. Changes in TEM1/endosialin expression in response to pro-angiogenic conditions were assessed in human endothelial cells grown in vitro. Intracranial U87MG glioblastoma (GBM) xenografts were analyzed in nude TEM1/endosialin knockout (KO) and wildtype (WT) mice. TEM1/endosialin was upregulated in primary and metastatic human brain tumors, where it localized primarily to the tumor vasculature and a subset of tumor stromal cells. Analysis of 275 arrayed grade II-IV astrocytomas demonstrated TEM1/endosialin expression in 79% of tumors. Robust TEM1/endosialin expression occurred in 31% of glioblastomas (grade IV astroctyomas). TEM1/endosialin expression was inversely correlated with patient age. TEM1/endosialin showed limited co-localization with CD31, αSMA and fibronectin in clinical specimens. In vitro, TEM1/endosialin was upregulated in human endothelial cells cultured in matrigel. Vascular Tem1/endosialin was induced in intracranial U87MG GBM xenografts grown in mice. Tem1/endosialin KO vs WT mice demonstrated equivalent survival and tumor growth when implanted with intracranial GBM xenografts, although Tem1/endosialin KO tumors were significantly more vascular than the WT counterparts. TEM1/endosialin was induced in the vasculature of high-grade brain tumors where its expression was inversely correlated with patient age. Although lack of TEM1/endosialin did not suppress growth of intracranial GBM xenografts, it did increase tumor vascularity. The cellular localization of TEM1

The anti-apoptotic effect of fluid mechanics preconditioning by cells membrane and mitochondria in rats brain microvascular endothelial cells.

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Tian, Shan; Zhu, Fengping; Hu, Ruiping; Tian, Song; Chen, Xingxing; Lou, Dan; Cao, Bing; Chen, Qiulei; Li, Bai; Li, Fang; Bai, Yulong; Wu, Yi; Zhu, Yulian

2018-01-01

Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface. Copyright © 2017 Elsevier B.V. All rights reserved.

Functional Response of Tumor Vasculature to PaCO2: Determination of Total and Microvascular Blood Volume by MRI

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Scott D. Packard

2003-07-01

Full Text Available In order to identify differences in functional activity, we compared the reactivity of glioma vasculature and the native cerebral vasculature to both dilate and constrict in response to altered PaCO2. Gliomas were generated by unilateral implantation of U87MGdEGFR human glioma tumor cells into the striatum of adult female athymic rats. Relative changes in total and microvascular cerebral blood volume were determined by steady state contrast agent-enhanced magnetic resonance imaging for transitions from normocarbia to hypercarbia and hypocarbia. Although hypercarbia induced a significant increase in both total and microvascular blood volume in normal brain and glioma, reactivity of glioma vasculature was significantly blunted in comparison to normal striatum; glioma total CBV increased by 0.6±0.1%/mm Hg CO2 whereas normal striatum increased by 1.5±0.2%/mm Hg CO2, (P < .0001, group t-test. Reactivity of microvascular blood volume was also significantly blunted. In contrast, hypocarbia decreased both total and microvascular blood volumes more in glioma than in normal striatum. These results indicate that cerebral blood vessels derived by tumor-directed angiogenesis do retain reactivity to CO2. Furthermore, reduced reactivity of tumor vessels to a single physiological perturbation, such as hypercarbia, should not be construed as a generalized reduction of functional activity of the tumor vascular bed.

Influenza H5N1 virus infection of polarized human alveolar epithelial cells and lung microvascular endothelial cells

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Yuen Kit M

2009-10-01

Full Text Available Abstract Background Highly pathogenic avian influenza (HPAI H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease. Aim To study influenza A (H5N1 virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease. Methods We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces. Results We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our

A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells

DEFF Research Database (Denmark)

Claessens, Antoine; Adams, Yvonne; Ghumra, Ashfaq

2012-01-01

Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterized by the accumulation of infected erythrocytes (IEs) in the microvasculature of the brain caused by parasite adhesins on the surface of IEs binding to human...... receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole transcriptome of isogenic pairs of selected.......029) but not by antibodies from controls with uncomplicated malaria (Mann-Whitney test, P = 0.58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria....

Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

Directory of Open Access Journals (Sweden)

Brandi D Freeman

2016-03-01

Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

Ebola virus glycoprotein-mediated anoikis of primary human cardiac microvascular endothelial cells

International Nuclear Information System (INIS)

Ray, Ratna B.; Basu, Arnab; Steele, Robert; Beyene, Aster; McHowat, Jane; Meyer, Keith; Ghosh, Asish K.; Ray, Ranjit

2004-01-01

Ebola virus glycoprotein (EGP) has been implicated for the induction of cytotoxicity and injury in vascular cells. On the other hand, EGP has also been suggested to induce massive cell rounding and detachment from the plastic surface by downregulating cell adhesion molecules without causing cytotoxicity. In this study, we have examined the cytotoxic role of EGP in primary endothelial cells by transduction with a replication-deficient recombinant adenovirus expressing EGP (Ad-EGP). Primary human cardiac microvascular endothelial cells (HCMECs) transduced with Ad-EGP displayed loss of cell adhesion from the plastic surface followed by cell death. Transfer of conditioned medium from EGP-transduced HCMEC into naive cells did not induce loss of adhesion or cell death, suggesting that EGP needs to be expressed intracellularly to exert its cytotoxic effect. Subsequent studies suggested that HCMEC death occurred through apoptosis. Results from this study shed light on the EGP-induced anoikis in primary human cardiac endothelial cells, which may have significant pathological consequences

Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans

Science.gov (United States)

Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Hargens, Alan R.

1993-01-01

The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous microcirculation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, O deg, -6 deg (HDT), -12 deg, -6 deg, O deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P less than 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.

Invasive assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy: the index of microvascular resistance

International Nuclear Information System (INIS)

Gutiérrez-Barrios, Alejandro; Camacho-Jurado, Francisco; Díaz-Retamino, Enrique; Gamaza-Chulián, Sergio; Agarrado-Luna, Antonio; Oneto-Otero, Jesús; Del Rio-Lechuga, Ana; Benezet-Mazuecos, Javier

2015-01-01

Summary: We present a review of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and an interesting case of a symptomatic familial HCM patient with inducible ischemia by single photon emission computed tomography. Coronary angiography revealed normal epicardial arteries. Pressure wire measurements of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microvascular resistance (IMR) demonstrated a significant microcirculatory dysfunction. This is the first such case that documents this abnormality invasively using the IMR. The measurement of IMR, a novel marker of microcirculatory dysfunction, provides novel insights into the pathophysiology of this condition. - Highlights: • Microvascular dysfunction is a common feature in hypertrophic cardiomyopathy (HCM) and represents a strong predictor of unfavorable outcome and cardiovascular mortality. • The index of microvascular resistance (IMR) is a new method for invasively assessing the state of the coronary microcirculation using a single pressure-temperature sensor-tipped coronary wire. • However assessment of IMR in HCM has not been previously reported. We report a case in which microvascular dysfunction is assessed by IMR. This index may be useful in future researches of HCM.

Invasive assessment of coronary microvascular dysfunction in hypertrophic cardiomyopathy: the index of microvascular resistance

Energy Technology Data Exchange (ETDEWEB)

Gutiérrez-Barrios, Alejandro, E-mail: aleklos@hotmail.com [Cardiology Department, Jerez Hospital, Jerez (Spain); Camacho-Jurado, Francisco [Cardiology Department, Punta Europa Hospital, Algeciras (Spain); Díaz-Retamino, Enrique; Gamaza-Chulián, Sergio; Agarrado-Luna, Antonio; Oneto-Otero, Jesús; Del Rio-Lechuga, Ana; Benezet-Mazuecos, Javier [Cardiology Department, Jerez Hospital, Jerez (Spain)

2015-10-15

Summary: We present a review of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and an interesting case of a symptomatic familial HCM patient with inducible ischemia by single photon emission computed tomography. Coronary angiography revealed normal epicardial arteries. Pressure wire measurements of fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microvascular resistance (IMR) demonstrated a significant microcirculatory dysfunction. This is the first such case that documents this abnormality invasively using the IMR. The measurement of IMR, a novel marker of microcirculatory dysfunction, provides novel insights into the pathophysiology of this condition. - Highlights: • Microvascular dysfunction is a common feature in hypertrophic cardiomyopathy (HCM) and represents a strong predictor of unfavorable outcome and cardiovascular mortality. • The index of microvascular resistance (IMR) is a new method for invasively assessing the state of the coronary microcirculation using a single pressure-temperature sensor-tipped coronary wire. • However assessment of IMR in HCM has not been previously reported. We report a case in which microvascular dysfunction is assessed by IMR. This index may be useful in future researches of HCM.

Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke

Science.gov (United States)

Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Carrera, David; Martí-Fàbregas, Joan; Durduran, Turgut

2014-01-01

The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.

ABCD1 dysfunction alters white matter microvascular perfusion

DEFF Research Database (Denmark)

Lauer, Arne; Da, Xiao; Hansen, Mikkel Bo

2017-01-01

Cerebral X-linked adrenoleukodystrophy is a devastating neurodegenerative disorder caused by mutations in the ABCD1 gene, which lead to a rapidly progressive cerebral inflammatory demyelination in up to 60% of affected males. Selective brain endothelial dysfunction and increased permeability...... of the blood–brain barrier suggest that white matter microvascular dysfunction contributes to the conversion to cerebral disease. Applying a vascular model to conventional dynamic susceptibility contrast magnetic reson- ance perfusion imaging, we demonstrate that lack of ABCD1 function causes increased...... capillary flow heterogeneity in asymptom- atic hemizygotes predominantly in the white matter regions and developmental stages with the highest probability for conversion to cerebral disease. In subjects with ongoing inflammatory demyelination we observed a sequence of increased capillary flow hetero...

Educating the Human Brain. Human Brain Development Series

Science.gov (United States)

Posner, Michael I.; Rothbart, Mary K.

2006-01-01

"Educating the Human Brain" is the product of a quarter century of research. This book provides an empirical account of the early development of attention and self regulation in infants and young children. It examines the brain areas involved in regulatory networks, their connectivity, and how their development is influenced by genes and…

Urokinase receptor expression on human microvascular endothelial cells is increased by hypoxia: Implications for capillary-like tube formation in a fibrin matrix

NARCIS (Netherlands)

Kroon, M.E.; Koolwijk, P.; Vecht, B. van der; Hinsbergh, V.W.M. van

2000-01-01

Hypoxia stimulates angiogenesis, the formation of new blood vessels. This study evaluates the direct effect of hypoxia (1% oxygen) on the angiogenic response of human microvascular endothelial cells (hMVECs) seeded on top of a 3-dimensional fibrin matrix, hMVECs stimulated with fibroblast growth

Experimental validation of the predicted binding site of Escherichia coli K1 outer membrane protein A to human brain microvascular endothelial cells: identification of critical mutations that prevent E. coli meningitis.

Science.gov (United States)

Pascal, Tod A; Abrol, Ravinder; Mittal, Rahul; Wang, Ying; Prasadarao, Nemani V; Goddard, William A

2010-11-26

Escherichia coli K1, the most common cause of meningitis in neonates, has been shown to interact with GlcNAc1-4GlcNAc epitopes of Ecgp96 on human brain microvascular endothelial cells (HBMECs) via OmpA (outer membrane protein A). However, the precise domains of extracellular loops of OmpA interacting with the chitobiose epitopes have not been elucidated. We report the loop-barrel model of these OmpA interactions with the carbohydrate moieties of Ecgp96 predicted from molecular modeling. To test this model experimentally, we generated E. coli K1 strains expressing OmpA with mutations of residues predicted to be critical for interaction with the HBMEC and tested E. coli invasion efficiency. For these same mutations, we predicted the interaction free energies (including explicit calculation of the entropy) from molecular dynamics (MD), finding excellent correlation (R(2) = 90%) with experimental invasion efficiency. Particularly important is that mutating specific residues in loops 1, 2, and 4 to alanines resulted in significant inhibition of E. coli K1 invasion in HBMECs, which is consistent with the complete lack of binding found in the MD simulations for these two cases. These studies suggest that inhibition of the interactions of these residues of Loop 1, 2, and 4 with Ecgp96 could provide a therapeutic strategy to prevent neonatal meningitis due to E. coli K1.

Human brain imaging

International Nuclear Information System (INIS)

Kuhar, M.J.

1987-01-01

Just as there have been dramatic advances in the molecular biology of the human brain in recent years, there also have been remarkable advances in brain imaging. This paper reports on the development and broad application of microscopic imaging techniques which include the autoradiographic localization of receptors and the measurement of glucose utilization by autoradiography. These approaches provide great sensitivity and excellent anatomical resolution in exploring brain organization and function. The first noninvasive external imaging of receptor distributions in the living human brain was achieved by positron emission tomography (PET) scanning. Developments, techniques and applications continue to progress. Magnetic resonance imaging (MRI) is also becoming important. Its initial clinical applications were in examining the structure and anatomy of the brain. However, more recent uses, such as MRI spectroscopy, indicate the feasibility of exploring biochemical pathways in the brain, the metabolism of drugs in the brain, and also of examining some of these procedures at an anatomical resolution which is substantially greater than that obtainable by PET scanning. The issues will be discussed in greater detail

Acute limb heating improves macro- and microvascular dilator function in the leg of aged humans.

Science.gov (United States)

Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Cramer, Matthew N; Kouda, Ken; Crandall, Craig G

2017-01-01

Local heating of an extremity increases blood flow and vascular shear stress throughout the arterial tree. Local heating acutely improves macrovascular dilator function in the upper limbs of young healthy adults through a shear stress-dependent mechanism but has no such effect in the lower limbs of this age group. The effect of acute limb heating on dilator function within the atherosclerotic prone vasculature of the lower limbs of aged adults is unknown. Therefore, the purpose of this study was to test the hypothesis that acute lower limb heating improves macro- and microvascular dilator function within the leg vasculature of aged adults. Nine young and nine aged adults immersed their lower limbs at a depth of ~33 cm into a heated (~42°C) circulated water bath for 45 min. Before and 30 min after heating, macro (flow-mediated dilation)- and microvascular (reactive hyperemia) dilator functions were assessed in the lower limb, following 5 min of arterial occlusion, via Doppler ultrasound. Compared with preheat, macrovascular dilator function was unchanged following heating in young adults (P = 0.6) but was improved in aged adults (P = 0.04). Similarly, microvascular dilator function, as assessed by peak reactive hyperemia, was unchanged following heating in young adults (P = 0.1) but was improved in aged adults (P lower limb heating improves both macro- and microvascular dilator function in an age dependent manner. We demonstrate that lower limb heating acutely improves macro- and microvascular dilator function within the atherosclerotic prone vasculature of the leg in aged adults. These findings provide evidence for a potential therapeutic use of chronic lower limb heating to improve vascular health in primary aging and various disease conditions. Copyright © 2017 the American Physiological Society.

Brain Evolution and Human Neuropsychology: The Inferential Brain Hypothesis

Science.gov (United States)

Koscik, Timothy R.; Tranel, Daniel

2013-01-01

Collaboration between human neuropsychology and comparative neuroscience has generated invaluable contributions to our understanding of human brain evolution and function. Further cross-talk between these disciplines has the potential to continue to revolutionize these fields. Modern neuroimaging methods could be applied in a comparative context, yielding exciting new data with the potential of providing insight into brain evolution. Conversely, incorporating an evolutionary base into the theoretical perspectives from which we approach human neuropsychology could lead to novel hypotheses and testable predictions. In the spirit of these objectives, we present here a new theoretical proposal, the Inferential Brain Hypothesis, whereby the human brain is thought to be characterized by a shift from perceptual processing to inferential computation, particularly within the social realm. This shift is believed to be a driving force for the evolution of the large human cortex. PMID:22459075

Neocortical Transplants in the Mammalian Brain Lack a Blood-Brain Barrier to Macromolecules

Science.gov (United States)

Rosenstein, Jeffrey M.

1987-02-01

In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.

Brain anatomical networks in early human brain development.

Science.gov (United States)

Fan, Yong; Shi, Feng; Smith, Jeffrey Keith; Lin, Weili; Gilmore, John H; Shen, Dinggang

2011-02-01

Recent neuroimaging studies have demonstrated that human brain networks have economic small-world topology and modular organization, enabling efficient information transfer among brain regions. However, it remains largely unknown how the small-world topology and modular organization of human brain networks emerge and develop. Using longitudinal MRI data of 28 healthy pediatric subjects, collected at their ages of 1 month, 1 year, and 2 years, we analyzed development patterns of brain anatomical networks derived from morphological correlations of brain regional volumes. The results show that the brain network of 1-month-olds has the characteristically economic small-world topology and nonrandom modular organization. The network's cost efficiency increases with the brain development to 1 year and 2 years, so does the modularity, providing supportive evidence for the hypothesis that the small-world topology and the modular organization of brain networks are established during early brain development to support rapid synchronization and information transfer with minimal rewiring cost, as well as to balance between local processing and global integration of information. Copyright © 2010. Published by Elsevier Inc.

Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells.

Science.gov (United States)

Uchida, Yasuo; Ito, Katsuaki; Ohtsuki, Sumio; Kubo, Yoshiyuki; Suzuki, Takashi; Terasaki, Tetsuya

2015-07-01

The purpose of this study was to clarify the expression of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) and its contribution to the supply of biotin and pantothenic acid to the human brain via the blood-brain barrier. DNA microarray and immunohistochemical analyses confirmed that SLC5A6 is expressed in microvessels of human brain. The absolute expression levels of SLC5A6 protein in isolated human and monkey brain microvessels were 1.19 and 0.597 fmol/μg protein, respectively, as determined by a quantitative targeted absolute proteomics technique. Using an antibody-free method established by Kubo et al. (2015), we found that SLC5A6 was preferentially localized at the luminal membrane of brain capillary endothelium. Knock-down analysis using SLC5A6 siRNA showed that SLC5A6 accounts for 88.7% and 98.6% of total [(3) H]biotin and [(3) H]pantothenic acid uptakes, respectively, by human cerebral microvascular endothelial cell line hCMEC/D3. SLC5A6-mediated transport in hCMEC/D3 was markedly inhibited not only by biotin and pantothenic acid, but also by prostaglandin E2, lipoic acid, docosahexaenoic acid, indomethacin, ketoprofen, diclofenac, ibuprofen, phenylbutazone, and flurbiprofen. This study is the first to confirm expression of SLC5A6 in human brain microvessels and to provide evidence that SLC5A6 is a major contributor to luminal uptake of biotin and pantothenic acid at the human blood-brain barrier. In humans, it was unclear (not concluded) about what transport system at the blood-brain barrier (BBB) is responsible for the brain uptakes of two vitamins, biotin and pantothenic acid, which are necessary for brain proper function. This study clarified for the first time that the solute carrier 5A6/Na(+) -dependent multivitamin transporter SLC5A6/SMVT is responsible for the supplies of biotin and pantothenic acid into brain across the BBB in humans. DHA, docosahexaenoic acid; NSAID, non-steroidal anti-inflammatory drug; PGE2, prostaglandin E2. © 2015

Tick-borne encephalitis virus infects human brain microvascular endothelial cells without compromising blood-brain barrier integrity

Czech Academy of Sciences Publication Activity Database

Palus, Martin; Vancová, Marie; Širmarová, J.; Elsterová, Jana; Perner, Jan; Růžek, Daniel

2017-01-01

Roč. 507, JUL (2017), s. 110-122 ISSN 0042-6822 R&D Projects: GA MZd(CZ) NV16-34238A; GA MŠk(CZ) LM2015062; GA TA ČR(CZ) TE01020118 Institutional support: RVO:60077344 Keywords : tick-borne encephalitis * tick-borne encephalitis virus * blood- brain barrier * neuroinfection Subject RIV: EE - Microbiology, Virology OBOR OECD: Virology Impact factor: 3.353, year: 2016

Cultivation of Human Microvascular Endothelial Cells on Topographical Substrates to Mimic the Human Corneal Endothelium

Directory of Open Access Journals (Sweden)

Jie Shi Chua

2013-03-01

Full Text Available Human corneal endothelial cells have a limited ability to replicate in vivo and in vitro. Allograft transplantation becomes necessary when an accident or trauma results in excessive cell loss. The reconstruction of the cornea endothelium using autologous cell sources is a promising alternative option for therapeutic or in vitro drug testing applications. The native corneal endothelium rests on the Descemet’s membrane, which has nanotopographies of fibers and pores. The use of synthetic topographies mimics the native environment, and it is hypothesized that this can direct the behavior and growth of human microvascular endothelial cells (HMVECs to resemble the corneal endothelium. In this study, HMVECs are cultivated on substrates with micron and nano-scaled pillar and well topographies. Closely packed HMVEC monolayers with polygonal cells and well-developed tight junctions were formed on the topographical substrates. Sodium/potassium (Na+/K+ adenine triphosphatase (ATPase expression was enhanced on the microwells substrate, which also promotes microvilli formation, while more hexagonal-like cells are found on the micropillars samples. The data obtained suggests that the use of optimized surface patterning, in particular, the microtopographies, can induce HMVECs to adopt a more corneal endothelium-like morphology with similar barrier and pump functions. The mechanism involved in cell contact guidance by the specific topographical features will be of interest for future studies.

Brain Activity and Human Unilateral Chewing

Science.gov (United States)

Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

2012-01-01

Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

Why did humans develop a large brain?

OpenAIRE

Muscat Baron, Yves

2012-01-01

"Of all animals, man has the largest brain in proportion to his size"- Aristotle. Dr Yves Muscat Baron shares his theory on how humans evolved large brains. The theory outlines how gravity could have helped humans develop a large brain- the author has named the theory 'The Gravitational Vascular Theory'. http://www.um.edu.mt/think/why-did-humans-develop-a-large-brain/

Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development

Directory of Open Access Journals (Sweden)

Samuel Sances

2018-04-01

Full Text Available Summary: Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition. : Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development. Keywords: organ-on-chip, spinal cord, iPSC, disease modeling, amyotrophic lateral sclerosis, microphysiological system, brain microvascular endothelial cells, spinal motor neurons, vasculature, microfluidic device

Micro-engineering a platform to reconstruct physiology and functionality of the human brain microvasculature in vitro

Science.gov (United States)

Daghighi, Yasaman; Heidari, Hossein; Taylor, Hayden

2018-02-01

A predominant unsolved challenge in tissue engineering is the need of a robust technique for producing vascular networks, particularly when modeling human brain tissue. The availability of reliable in vitro human brain microvasculature models would advance our understanding of its function and would provide a platform for highthroughput drug screening. Current strategies for modeling vascularized brain tissue suffer from limitations such as (1) culturing non-human cell lines, (2) limited multi-cell co-culture, and (3) the effects of neighboring physiologically unrealistic rigid polymeric surfaces, such as solid membranes. We demonstrate a new micro-engineered platform that can address these shortcomings. Specifically, we have designed and prototyped a molding system to enable the precise casting of 100μm-diameter coaxial hydrogel structures laden with the requisite cells to mimic a vascular lumen. Here we demonstrate that a fine wire with diameter 130 μm or a needle with outer diameter 300 μm can be used as a temporary mold insert, and agarose-collagen composite matrix can be cast around these inserts and thermally gelled. When the wire or needle is retracted under the precise positional control afforded by our system, a microchannel is formed which is then seeded with human microvascular endothelial cells. After seven days of culture these cells produce an apparently confluent monolayer on the channel walls. In principle, this platform could be used to create multilayered cellular structures. By arranging a fine wire and a hollow needle coaxially, three distinct zones could be defined in the model: first, the bulk gel surrounding the needle; then, after needle retraction, a cylindrical shell of matrix; and finally, after retraction of the wire, a lumen. Each zone could be independently cell-seeded. To this end, we have also successfully 3D cultured human astrocytes and SY5Y glial cells in our agarose-collagen matrix. Our approach ultimately promises scalable

α-Klotho expression determines nitric oxide synthesis in response to FGF-23 in human aortic endothelial cells.

Directory of Open Access Journals (Sweden)

Chih-Ping Chung

Full Text Available Endothelial cells (ECs express fibroblast growth factor (FGF receptors and are metabolically active after treatment with FGF-23. It is not known if this effect is α-Klotho independent or mediated by humoral or endogenous endothelial α-Klotho. In the present study, we aimed to characterize EC α-Klotho expression within the human vascular tree and to investigate the potential role of α-Klotho in determining FGF-23 mediated EC regulation. Human tissue and ECs from various organs were used for immunohistochemistry and Western blot. Primary cultures of human aortic endothelial cells (HAECs and human brain microvascular endothelial cells (HBMECs were used to generate in vitro cell models. We found endogenous α-Klotho expression in ECs from various organs except in microvascular ECs from human brain. Furthermore, FGF-23 stimulated endothelial nitric oxide synthase (eNOS expression, nitric oxide (NO production, and cell proliferation in HAECs. Interestingly, these effects were not observed in our HBMEC model in vitro. High phosphate treatment and endothelial α-Klotho knockdown mitigated FGF-23 mediated eNOS induction, NO production, and cell proliferation in HAECs. Rescue treatment with soluble α-Klotho did not reverse endothelial FGF-23 resistance caused by reduced or absent α-Klotho expression in HAECs. These novel observations provide evidence for differential α-Klotho functional expression in the human endothelium and its presence may play a role in determining the response to FGF-23 in the vascular tree. α-Klotho was not detected in cerebral microvascular ECs and its absence may render these cells nonresponsive to FGF-23.

Differentiation state determines neural effects on microvascular endothelial cells

International Nuclear Information System (INIS)

Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

2012-01-01

Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. ► Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. ► Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. ► Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell production of nitric oxide. ► Neural progenitor cells and dorsal root

Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

Institute of Scientific and Technical Information of China (English)

HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

2005-01-01

Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

Protein phosphorylation systems in postmortem human brain

International Nuclear Information System (INIS)

Walaas, S.I.; Perdahl-Wallace, E.; Winblad, B.; Greengard, P.

1989-01-01

Protein phosphorylation systems regulated by cyclic adenosine 3',5'-monophosphate (cyclic AMP), or calcium in conjunction with calmodulin or phospholipid/diacylglycerol, have been studied by phosphorylation in vitro of particulate and soluble fractions from human postmortem brain samples. One-dimensional or two-dimensional gel electrophoretic protein separations were used for analysis. Protein phosphorylation catalyzed by cyclic AMP-dependent protein kinase was found to be highly active in both particulate and soluble preparations throughout the human CNS, with groups of both widely distributed and region-specific substrates being observed in different brain nuclei. Dopamine-innervated parts of the basal ganglia and cerebral cortex contained the phosphoproteins previously observed in rodent basal ganglia. In contrast, calcium/phospholipid-dependent and calcium/calmodulin-dependent protein phosphorylation systems were less prominent in human postmortem brain than in rodent brain, and only a few widely distributed substrates for these protein kinases were found. Protein staining indicated that postmortem proteolysis, particularly of high-molecular-mass proteins, was prominent in deeply located, subcortical regions in the human brain. Our results indicate that it is feasible to use human postmortem brain samples, when obtained under carefully controlled conditions, for qualitative studies on brain protein phosphorylation. Such studies should be of value in studies on human neurological and/or psychiatric disorders

Male microchimerism in the human female brain.

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William F N Chan

Full Text Available In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus. Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n=26, or women who had Alzheimer's disease (n=33. We report that 63% of the females (37 of 59 tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p=0.03 and concentration (p=0.06 of male microchimerism in the brains of women with Alzheimer's disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.

Rat Pial Microvascular Changes During Cerebral Blood Flow Decrease and Recovery: Effects of Cyanidin Administration

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Teresa Mastantuono

2018-05-01

Full Text Available The reactive oxygen species (ROS are known to play a major role in many pathophysiological conditions, such as ischemia and reperfusion injury. The present study was aimed to evaluate the in vivo cyanidin (anthocyanin effects on damages induced by rat pial microvascular hypoperfusion-reperfusion injury by cerebral blood flow decrease (CBFD and subsequent cerebral blood flow recovery (CBFR. In particular, the main purpose was to detect changes in ROS production after cyanidin administration. Rat pial microvasculature was investigated using fluorescence microscopy through a cranial window (closed; Strahler's method was utilized to define the geometric features of pial vessels. ROS production was investigated in vivo by 2′-7′-dichlorofluorescein-diacetate assay and neuronal damage was measured on isolated brain sections by 2,3,5-triphenyltetrazolium chloride staining. After 30 min of CBFD, induced by bilateral common carotid artery occlusion, and 60 min of CBFR, rats showed decrease of arteriolar diameter and capillary perfusion; furthermore, increase in microvascular leakage and leukocyte adhesion was observed. Conversely, cyanidin administration induced dose-related arteriolar dilation, reduction in microvascular permeability as well as leukocyte adhesion when compared to animals subjected to restriction of cerebral blood flow; moreover, capillary perfusion was protected. ROS generation increase and marked neuronal damage were detected in animals subjected to CBFD and CBFR. On the other hand, cyanidin was able to reduce ROS generation and neuronal damage. In conclusion, cyanidin treatment showed dose-related protective effects on rat pial microcirculation during CBFD and subsequent CBFR, inducing arteriolar dilation by nitric oxide release and inhibiting ROS formation, consequently preserving the blood brain barrier integrity.

Tumor necrosis factor-alpha increases myocardial microvascular transport in vivo

DEFF Research Database (Denmark)

Hansen, P R; Svendsen, Jesper Hastrup; Høyer, S

1994-01-01

Tumor necrosis factor-alpha (TNF-alpha) is a primary mediator in the pathogenesis of tissue injury, and high circulating levels of TNF-alpha are found in a variety of pathological conditions. In open-chest anesthetized dogs, the effects of intracoronary recombinant human TNF-alpha (rTNF-alpha; 100...... in cardiac output and was associated with the appearance of areas with myocardial necrosis in the regional left ventricular wall. The myocardial plasma flow rate and maximum plasma flow rate in response to a 30-s coronary occlusion were not influenced by rTNF-alpha, although a decrease in the myocardial...... ng/kg for 60 min) on myocardial microvascular transport of a small hydrophilic indicator was examined by the single-injection, residue-detection method. Intracoronary infusion of rTNF-alpha increased myocardial microvascular transport after 120 min. This increase was preceded by a sustained decline...

Tetramethylpyrazine Protects Against Oxygen-Glucose Deprivation-Induced Brain Microvascular Endothelial Cells Injury via Rho/Rho-kinase Signaling Pathway.

Science.gov (United States)

Yang, Guang; Qian, Chen; Wang, Ning; Lin, Chenyu; Wang, Yan; Wang, Guangyun; Piao, Xinxin

2017-05-01

Tetramethylpyrazine (TMP, also known as Ligustrazine), which is isolated from Chinese Herb Medicine Ligustium wollichii Franchat (Chuan Xiong), has been widely used in China for the treatment of ischemic stroke by Chinese herbalists. Brain microvascular endothelial cells (BMECs) are the integral parts of the blood-brain barrier (BBB), protecting BMECs against oxygen-glucose deprivation (OGD) which is important for the treatment of ischemic stroke. Here, we investigated the protective mechanisms of TMP, focusing on OGD-injured BMECs and the Rho/Rho-kinase (Rho-associated kinases, ROCK) signaling pathway. The model of OGD-injured BMECs was established in this study. BMECs were identified by von Willebrand factor III staining and exposed to fasudil, or TMP at different concentrations (14.3, 28.6, 57.3 µM) for 2 h before 24 h of OGD injury. The effect of each treatment was examined by cell viability assays, measurement of intracellular reactive oxygen species (ROS), and transendothelial electric resistance and western blot analysis (caspase-3, endothelial nitric oxide synthase (eNOS), RhoA, Rac1). Our results show that TMP significantly attenuated apoptosis and the permeability of BMECs induced by OGD. In addition, TMP could notably down-regulate the characteristic proteins in Rho/ROCK signaling pathway such as RhoA and Rac1, which triggered abnormal changes of eNOS and ROS, respectively. Altogether, our results show that TMP has a strong protective effect against OGD-induced BMECs injury and suggest that the mechanism might be related to the inhibition of the Rho/ROCK signaling pathway.

BrainNet Viewer: a network visualization tool for human brain connectomics.

Science.gov (United States)

Xia, Mingrui; Wang, Jinhui; He, Yong

2013-01-01

The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/).

BrainNet Viewer: a network visualization tool for human brain connectomics.

Directory of Open Access Journals (Sweden)

Mingrui Xia

Full Text Available The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI, we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/.

Conscious brain-to-brain communication in humans using non-invasive technologies.

Science.gov (United States)

Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L; Pascual-Leone, Alvaro; Ruffini, Giulio

2014-01-01

Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

Conscious brain-to-brain communication in humans using non-invasive technologies.

Directory of Open Access Journals (Sweden)

Carles Grau

Full Text Available Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI. These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B communication between subjects (hyperinteraction. Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG changes with a CBI inducing the conscious perception of phosphenes (light flashes through neuronavigated, robotized transcranial magnetic stimulation (TMS, with special care taken to block sensory (tactile, visual or auditory cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

Platelets alter gene expression profile in human brain endothelial cells in an in vitro model of cerebral malaria.

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Mathieu Barbier

Full Text Available Platelet adhesion to the brain microvasculature has been associated with cerebral malaria (CM in humans, suggesting that platelets play a role in the pathogenesis of this syndrome. In vitro co-cultures have shown that platelets can act as a bridge between Plasmodium falciparum-infected red blood cells (pRBC and human brain microvascular endothelial cells (HBEC and potentiate HBEC apoptosis. Using cDNA microarray technology, we analyzed transcriptional changes of HBEC in response to platelets in the presence or the absence of tumor necrosis factor (TNF and pRBC, which have been reported to alter gene expression in endothelial cells. Using a rigorous statistical approach with multiple test corrections, we showed a significant effect of platelets on gene expression in HBEC. We also detected a strong effect of TNF, whereas there was no transcriptional change induced specifically by pRBC. Nevertheless, a global ANOVA and a two-way ANOVA suggested that pRBC acted in interaction with platelets and TNF to alter gene expression in HBEC. The expression of selected genes was validated by RT-qPCR. The analysis of gene functional annotation indicated that platelets induce the expression of genes involved in inflammation and apoptosis, such as genes involved in chemokine-, TREM1-, cytokine-, IL10-, TGFβ-, death-receptor-, and apoptosis-signaling. Overall, our results support the hypothesis that platelets play a pathogenic role in CM.

Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction

International Nuclear Information System (INIS)

Nakao, Atsunori; Kaczorowski, David J.; Zuckerbraun, Brian S.; Lei Jing; Faleo, Gaetano; Deguchi, Kentaro; McCurry, Kenneth R.; Billiar, Timothy R.; Kanno, Shinichi

2008-01-01

Galantamine, a reversible inhibitor of acetylcholine esterase (AChE), is a novel drug treatment for mild to moderate Alzheimer's disease and vascular dementia. Interestingly, it has been suggested that galantamine treatment is associated with more clinical benefit in patients with mild-to-moderate Alzheimer disease compared to other AChE inhibitors. We hypothesized that the protective effects of galantamine would involve induction of the protective gene, heme oxygenase-1 (HO-1), in addition to enhancement of the cholinergic system. Brain microvascular endothelial cells (mvECs) were isolated from spontaneous hypertensive rats. Galantamine significantly reduced H 2 O 2 -induced cell death of mvECs in association with HO-1 induction. These protective effects were completely reversed by nuclear factor-κB (NF-κB) inhibition or HO inhibition. Furthermore, galantamine failed to induce HO-1 in mvECs which lack inducible nitric oxide synthase (iNOS), supplementation of a nitric oxide (NO) donor or iNOS gene transfection on iNOS-deficient mvECs resulted in HO-1 induction with galantamine. These data suggest that the protective effects of galantamine require NF-κB activation and iNOS expression, in addition to HO-1. Likewise, carbon monoxide (CO), one of the byproducts of HO, up-regulated HO-1 and protected mvECs from oxidative stress in a similar manner. Our data demonstrate that galantamine mediates cytoprotective effects on mvECs through induction HO-1. This pharmacological action of galantamine may, at least in part, account for the superior clinical efficacy of galantamine in vascular dementia and Alzheimer disease

Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability.

Science.gov (United States)

Qian, Yong; Ducatman, Alan; Ward, Rebecca; Leonard, Steve; Bukowski, Valerie; Lan Guo, Nancy; Shi, Xianglin; Vallyathan, Val; Castranova, Vincent

2010-01-01

Perfluorooctane sulfonate (PFOS) is a member of the perfluoroalkyl acids (PFAA) containing an eight-carbon backbone. PFOS is a man-made chemical with carbon-fluorine bonds that are among the strongest in organic chemistry, and PFOS is widely used in industry. Human occupational and environmental exposure to PFOS occurs globally. PFOS is non-biodegradable and is persistent in the human body and environment. In this study, data demonstrated that exposure of human microvascular endothelial cells (HMVEC) to PFOS induced the production of reactive oxygen species (ROS) at both high and low concentrations. Morphologically, it was found that exposure to PFOS induced actin filament remodeling and endothelial permeability changes in HMVEC. Furthermore, data demonstrated that the production of ROS plays a regulatory role in PFOS-induced actin filament remodeling and the increase in endothelial permeability. Our results indicate that the generation of ROS may play a role in PFOS-induced aberrations of the endothelial permeability barrier. The results generated from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans at the cellular level.

Computational Intelligence in a Human Brain Model

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Viorel Gaftea

2016-06-01

Full Text Available This paper focuses on the current trends in brain research domain and the current stage of development of research for software and hardware solutions, communication capabilities between: human beings and machines, new technologies, nano-science and Internet of Things (IoT devices. The proposed model for Human Brain assumes main similitude between human intelligence and the chess game thinking process. Tactical & strategic reasoning and the need to follow the rules of the chess game, all are very similar with the activities of the human brain. The main objective for a living being and the chess game player are the same: securing a position, surviving and eliminating the adversaries. The brain resolves these goals, and more, the being movement, actions and speech are sustained by the vital five senses and equilibrium. The chess game strategy helps us understand the human brain better and easier replicate in the proposed ‘Software and Hardware’ SAH Model.

Optical clearing and fluorescence deep-tissue imaging for 3D quantitative analysis of the brain tumor microenvironment

NARCIS (Netherlands)

Lagerweij, Tonny; Dusoswa, Sophie A.; Negrean, Adrian; Hendrikx, Esther M.L.; de Vries, Helga E.; Kole, Jeroen; Garcia-Vallejo, Juan J.; Mansvelder, Huibert D; Vandertop, W. Peter; Noske, David P.; Tannous, Bakhos A.; Musters, René J P; van Kooyk, Yvette; Wesseling, Pieter; Zhao, Xi Wen; Wurdinger, Thomas

2017-01-01

Background: Three-dimensional visualization of the brain vasculature and its interactions with surrounding cells may shed light on diseases where aberrant microvascular organization is involved, including glioblastoma (GBM). Intravital confocal imaging allows 3D visualization of microvascular

Phosphatidylserine and the human brain.

Science.gov (United States)

Glade, Michael J; Smith, Kyl

2015-06-01

The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function. A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review. A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability. Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes. Copyright © 2015 Elsevier Inc. All rights reserved.

Microvascular responses to (hyper-)gravitational stress by short-arm human centrifuge: arteriolar vasoconstriction and venous pooling.

Science.gov (United States)

Habazettl, H; Stahn, Alexander; Nitsche, Andrea; Nordine, Michael; Pries, A R; Gunga, H-C; Opatz, O

2016-01-01

We hypothesized that lower body microvessels are particularly challenged during exposure to gravity and hypergravity leading to failure of resistance vessels to withstand excessive transmural pressure during hypergravitation and gravitation-dependent microvascular blood pooling. Using a short-arm human centrifuge (SAHC), 12 subjects were exposed to +1Gz, +2Gz and +1Gz, all at foot level, for 4 min each. Laser Doppler imaging and near-infrared spectroscopy were used to measure skin perfusion and tissue haemoglobin concentrations, respectively. Pretibial skin perfusion decreased by 19% during +1Gz and remained at this level during +2Gz. In the dilated area, skin perfusion increased by 24 and 35% during +1Gz and +2Gz, respectively. In the upper arm, oxygenated haemoglobin (Hb) decreased, while deoxy Hb increased with little change in total Hb. In the calf muscle, O2Hb and deoxy Hb increased, resulting in total Hb increase by 7.5 ± 1.4 and 26.6 ± 2.6 µmol/L at +1Gz and +2Gz, respectively. The dynamics of Hb increase suggests a fast and a slow component. Despite transmural pressures well beyond the upper myogenic control limit, intact lower body resistance vessels withstand these pressures up to +2Gz, suggesting that myogenic control may contribute only little to increased vascular resistance. The fast component of increasing total Hb indicates microvascular blood pooling contributing to soft tissue capacitance. Future research will have to address possible alterations of these acute adaptations to gravity after deconditioning by exposure to micro-g.

Optical clearing and fluorescence deep-tissue imaging for 3D quantitative analysis of the brain tumor microenvironment

NARCIS (Netherlands)

Lagerweij, Tonny; Dusoswa, Sophie A.; Negrean, Adrian; Hendrikx, Esther M. L.; de Vries, Helga E.; Kole, Jeroen; Garcia-Vallejo, Juan J.; Mansvelder, Huibert D.; Vandertop, W. Peter; Noske, David P.; Tannous, Bakhos A.; Musters, René J. P.; van Kooyk, Yvette; Wesseling, Pieter; Zhao, Xi Wen; Wurdinger, Thomas

2017-01-01

Three-dimensional visualization of the brain vasculature and its interactions with surrounding cells may shed light on diseases where aberrant microvascular organization is involved, including glioblastoma (GBM). Intravital confocal imaging allows 3D visualization of microvascular structures and

Experimental diode laser-assisted microvascular anastomosis.

Science.gov (United States)

Reali, U M; Gelli, R; Giannotti, V; Gori, F; Pratesi, R; Pini, R

1993-05-01

An experimental study to evaluate a diode-laser approach to microvascular end-to-end anastomoses is reported. Studies were carried out on the femoral arteries and veins of Wistar rats, and effective welding of vessel tissue was obtained at low laser power, by enhancing laser absorption with indocyanine green (Cardio-green) solution. The histologic and surgical effects of this laser technique were examined and compared with those of conventional microvascular sutured anastomoses.

Cerebral Vascular Injury in Traumatic Brain Injury.

Science.gov (United States)

Kenney, Kimbra; Amyot, Franck; Haber, Margalit; Pronger, Angela; Bogoslovsky, Tanya; Moore, Carol; Diaz-Arrastia, Ramon

2016-01-01

Traumatic cerebral vascular injury (TCVI) is a very frequent, if not universal, feature after traumatic brain injury (TBI). It is likely responsible, at least in part, for functional deficits and TBI-related chronic disability. Because there are multiple pharmacologic and non-pharmacologic therapies that promote vascular health, TCVI is an attractive target for therapeutic intervention after TBI. The cerebral microvasculature is a component of the neurovascular unit (NVU) coupling neuronal metabolism with local cerebral blood flow. The NVU participates in the pathogenesis of TBI, either directly from physical trauma or as part of the cascade of secondary injury that occurs after TBI. Pathologically, there is extensive cerebral microvascular injury in humans and experimental animal, identified with either conventional light microscopy or ultrastructural examination. It is seen in acute and chronic TBI, and even described in chronic traumatic encephalopathy (CTE). Non-invasive, physiologic measures of cerebral microvascular function show dysfunction after TBI in humans and experimental animal models of TBI. These include imaging sequences (MRI-ASL), Transcranial Doppler (TCD), and Near InfraRed Spectroscopy (NIRS). Understanding the pathophysiology of TCVI, a relatively under-studied component of TBI, has promise for the development of novel therapies for TBI. Published by Elsevier Inc.

Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

Science.gov (United States)

Li, Guangye; Zhang, Dingguo

2016-01-01

An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

Distribution of melatonin receptor in human fetal brain

Institute of Scientific and Technical Information of China (English)

WANG Guo-quan; SHAO Fu-yuan; ZHAO Ying; LIU Zhi-min

2001-01-01

Objective: To study the distribution of 2 kinds of melatonin receptor subtypes (mtl and MT2) in human fetal brain. Methods: The fetal brain tissues were sliced and the distribution ofmelatonin receptors in human fetal brain were detected using immunohistochemistry and in situ hybridization. Results: Melatonin receptor mtl existed in the cerebellun and hypothalamus, melatonin receptor MT2 exists in hypothalamus, occipital and medulla. Conclusion: Two kinds of melatonin receptors, mtl and MT2 exist in the membrane and cytosol of brain cells, indicating that human fetal brain is a target organ of melatonin.

(−-Epigallocatechin gallate inhibits endotoxin-induced expression of inflammatory cytokines in human cerebral microvascular endothelial cells

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Li Jieliang

2012-07-01

Full Text Available Abstract Background (−-Epigallocatechin gallate (EGCG is a major polyphenol component of green tea that has antioxidant activities. Lipopolysaccharide (LPS induces inflammatory cytokine production and impairs blood–brain barrier (BBB integrity. We examined the effect of EGCG on LPS-induced expression of the inflammatory cytokines in human cerebral microvascular endothelial cells (hCMECs and BBB permeability. Methods The expression of TNF-α, IL-1β and monocyte chemotactic protein-1 (MCP-1/CCL2 was determined by quantitative real time PCR (qRT-PCR and ELISA. Intercellular adhesion molecule 1 (ICAM-1 and vascular cell adhesion molecule (VCAM in hCMECs were examined by qRT-PCR and Western blotting. Monocytes that adhered to LPS-stimulated endothelial cells were measured by monocyte adhesion assay. Tight junctional factors were detected by qRT-PCR (Claudin 5 and Occludin and immunofluorescence staining (Claudin 5 and ZO-1. The permeability of the hCMEC monolayer was determined by fluorescence spectrophotometry of transmembrane fluorescin and transendothelial electrical resistance (TEER. NF-kB activation was measured by luciferase assay. Results EGCG significantly suppressed the LPS-induced expression of IL-1β and TNF-α in hCMECs. EGCG also inhibited the expression of MCP-1/CCL2, VCAM-1 and ICAM-1. Functional analysis showed that EGCG induced the expression of tight junction proteins (Occludin and Claudin-5 in hCMECs. Investigation of the mechanism showed that EGCG had the ability to inhibit LPS-mediated NF-κB activation. In addition, 67-kD laminin receptor was involved in the anti-inflammatory effect of EGCG. Conclusions Our results demonstrated that LPS induced inflammatory cytokine production in hCMECs, which could be attenuated by EGCG. These data indicate that EGCG has a therapeutic potential for endotoxin-mediated endothelial inflammation.

Adipose tissue-derived microvascular fragments from aged donors exhibit an impaired vascularisation capacity

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MW Laschke

2014-10-01

Full Text Available Adipose tissue-derived microvascular fragments are promising vascularisation units for applications in the field of tissue engineering. Elderly patients are the major future target population of such applications due to an increasing human life expectancy. Therefore, we herein investigated the effect of aging on the fragments’ vascularisation capacity. Microvascular fragments were isolated from epididymal fat pads of adult (8 months and aged (16 months C57BL/6 donor mice. These fragments were seeded onto porous polyurethane scaffolds, which were implanted into dorsal skinfold chambers to study their vascularisation using intravital fluorescence microscopy, histology and immunohistochemistry. Scaffolds seeded with fragments from aged donors exhibited a significantly lower functional microvessel density and intravascular blood flow velocity. This was associated with an impaired vessel maturation, as indicated by vessel wall irregularities, constantly elevated diameters and a lower fraction of CD31/α-smooth muscle actin double positive microvessels in the implants’ border and centre zones. Additional in vitro analyses revealed that microvascular fragments from adult and aged donors do not differ in their stem cell content as well as in their release of angiogenic growth factors, survival and proliferative activity under hypoxic conditions. However, fragments from aged donors exhibit a significantly lower number of matrix metalloproteinase -9-positive perivascular cells. Taken together, these findings demonstrate that aging is a crucial determinant for the vascularisation capacity of isolated microvascular fragments.

Withaferin A promotes proliferation and migration of brain ...

African Journals Online (AJOL)

from the literature, we designed an experiment to study the effect of withaferin A on suppression of brain tumor growth in a nude mice model with an attempt to develop potent therapeutic agent. EXPERIMENTAL. Cell line and culture. The mouse brain microvascular endothelial cell line, BALB-5023 was purchased from the.

Positive selection on gene expression in the human brain

DEFF Research Database (Denmark)

Khaitovich, Philipp; Tang, Kun; Franz, Henriette

2006-01-01

Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

Endothelial progenitor cells physiology and metabolic plasticity in brain angiogenesis and blood-brain barrier modeling

Directory of Open Access Journals (Sweden)

Natalia Malinovskaya

2016-12-01

Full Text Available Currently, there is a considerable interest to the assessment of blood-brain barrier (BBB development as a part of cerebral angiogenesis developmental program. Embryonic and adult angiogenesis in the brain is governed by the coordinated activity of endothelial progenitor cells, brain microvascular endothelial cells, and non-endothelial cells contributing to the establishment of the BBB (pericytes, astrocytes, neurons. Metabolic and functional plasticity of endothelial progenitor cells controls their timely recruitment, precise homing to the brain microvessels, and efficient support of brain angiogenesis. Deciphering endothelial progenitor cells physiology would provide novel engineering approaches to establish adequate microfluidically-supported BBB models and brain microphysiological systems for translational studies.

Use of 125I-labeled human serum albumin for quantitation of microvascular permeability in rat skin: reevaluation of an old method for studies on substances with an enhancing effect on microvascular permeability

International Nuclear Information System (INIS)

Gerdin, B.

1981-01-01

A method of determining the leakage of 125I-labeled human serum albumin in the plasma into a standardized area of rat skin to study the effects of intracutaneous application of vasoactive substances on microvascular permeability, was reevaluated. The effect is expressed as a quotient (Q) between the amount of labeled albumin in the test area and that in an area injected with buffer. This calculation is simple and as reliable as more complicated expressions of activity. Within a limited dose range, linear/log dose-response curves can be obtained after application of histamine or bradykinin. Locally injected 125I-labeled human serum albumin is eliminated very slowly from rat skin and determination of the amount of radiolabeled albumin in skin after an intravenous injection therefore represents leakage from the vascular compartments. The potentialities and advantages of this method in pharmacological studies are stressed

Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet.

Science.gov (United States)

Suwannasual, Usa; Lucero, JoAnn; McDonald, Jacob D; Lund, Amie K

2018-01-01

Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy 3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were exacerbated by a high-fat (HF) vs. low-fat (LF) diet. Mice on each diet were randomly assigned to be exposed to either filtered air (FA) or MVE [100PM/m 3 vehicle emissions mixture: 30µg PM/m 3 gasoline engine + 70µg PM/m 3 diesel engine emissions; median size ~ 60nm; particle mass size distribution median of ~ 1µm (range: diet, results in altered BBB integrity and increased ox-LDL signaling in the cerebral vasculature in a wildtype animal model. Copyright © 2017 Elsevier Inc. All rights reserved.

Defense at the border : the blood-brain barrier versus bacterial foreigners

NARCIS (Netherlands)

van Sorge, Nina M.; Doran, Kelly S.

Bacterial meningitis is among the top ten causes of infectious disease-related deaths worldwide, with up to half of the survivors left with permanent neurological sequelae. The blood-brain barrier (BBB), composed mainly of specialized brain microvascular endothelial cells, maintains biochemical

Glucose transporter of the human brain and blood-brain barrier

International Nuclear Information System (INIS)

Kalaria, R.N.; Gravina, S.A.; Schmidley, J.W.; Perry, G.; Harik, S.I.

1988-01-01

We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species

Activation of melatonin receptor (MT1/2) promotes P-gp transporter in methamphetamine-induced toxicity on primary rat brain microvascular endothelial cells.

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Jumnongprakhon, Pichaya; Sivasinprasasn, Sivanan; Govitrapong, Piyarat; Tocharus, Chainarong; Tocharus, Jiraporn

2017-06-01

Melatonin has been known as a neuroprotective agent for the central nervous system (CNS) and the blood-brain barrier (BBB), which is the primary structure that comes into contact with several neurotoxins including methamphetamine (METH). Previous studies have reported that the activation of melatonin receptors (MT1/2) by melatonin could protect against METH-induced toxicity in brain endothelial cells via several mechanisms. However, its effects on the P-glycoprotein (P-gp) transporter, the active efflux pump involved in cell homeostasis, are still unclear. Thus, this study investigated the role of melatonin and its receptors on the METH-impaired P-gp transporter in primary rat brain microvascular endothelial cells (BMVECs). The results showed that METH impaired the function of the P-gp transporter, significantly decreasing the efflux of Rho123 and P-gp expression, which caused a significant increase in the intracellular accumulation of Rho123, and these responses were reversed by the interaction of melatonin with its receptors. Blockade of the P-gp transporter by verapamil caused oxidative stress, apoptosis, and cell integrity impairment after METH treatment, and these effects could be reversed by melatonin. Our results, together with previous findings, suggest that the interaction of melatonin with its receptors protects against the effects of the METH-impaired P-gp transporter and that the protective role in METH-induced toxicity was at least partially mediated by the regulation of the P-gp transporter. Thus, melatonin and its receptors (MT1/2) are essential for protecting against BBB impairment caused by METH. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlates of time to microvascular complications among diabetes ...

African Journals Online (AJOL)

Socio-demographic and clinical factors have been known to affect the time to microvascular complications and survival probabilities of diabetes mellitus patients. The objective of this study was to identify risk factors and estimate average survival times for the time to the development of microvascular complications of ...

Microvascular pericytes in healthy and diseased kidneys

Science.gov (United States)

Pan, Szu-Yu; Chang, Yu-Ting; Lin, Shuei-Liong

2014-01-01

Pericytes are interstitial mesenchymal cells found in many major organs. In the kidney, microvascular pericytes are defined anatomically as extensively branched, collagen-producing cells in close contact with endothelial cells. Although many molecular markers have been proposed, none of them can identify the pericytes with satisfactory specificity or sensitivity. The roles of microvascular pericytes in kidneys were poorly understood in the past. Recently, by using genetic lineage tracing to label collagen-producing cells or mesenchymal cells, the elusive characteristics of the pericytes have been illuminated. The purpose of this article is to review recent advances in the understanding of microvascular pericytes in the kidneys. In healthy kidney, the pericytes are found to take part in the maintenance of microvascular stability. Detachment of the pericytes from the microvasculature and loss of the close contact with endothelial cells have been observed during renal insult. Renal microvascular pericytes have been shown to be the major source of scar-forming myofibroblasts in fibrogenic kidney disease. Targeting the crosstalk between pericytes and neighboring endothelial cells or tubular epithelial cells may inhibit the pericyte–myofibroblast transition, prevent peritubular capillary rarefaction, and attenuate renal fibrosis. In addition, renal pericytes deserve attention for their potential to produce erythropoietin in healthy kidneys as pericytes stand in the front line, sensing the change of oxygenation and hemoglobin concentration. Further delineation of the mechanisms underlying the reduced erythropoietin production occurring during pericyte–myofibroblast transition may be promising for the development of new treatment strategies for anemia in chronic kidney disease. PMID:24465134

Interleukin 6-Mediated Endothelial Barrier Disturbances Can Be Attenuated by Blockade of the IL6 Receptor Expressed in Brain Microvascular Endothelial Cells.

Science.gov (United States)

Blecharz-Lang, Kinga G; Wagner, Josephin; Fries, Alexa; Nieminen-Kelhä, Melina; Rösner, Jörg; Schneider, Ulf C; Vajkoczy, Peter

2018-02-10

Compromised blood-brain barrier (BBB) by dysregulation of cellular junctions is a hallmark of many cerebrovascular disorders due to the pro-inflammatory cytokines action. Interleukin 6 (IL6) is implicated in inflammatory processes and in secondary brain injury after subarachnoid hemorrhage (SAH) but its role in the maintenance of cerebral endothelium still requires a precise elucidation. Although IL6 has been shown to exert pro-inflammatory action on brain microvascular endothelial cells (ECs), the expression of one of the IL6 receptors, the IL6R is controversially discussed. In attempt to reach more clarity in this issue, we present here an evident baseline expression of the IL6R in BBB endothelium in vivo and in an in vitro model of the BBB, the cEND cell line. A significantly increased expression of IL6R and its ligand was observed in BBB capillaries 2 days after experimental SAH in mice. In vitro, we saw IL6 administration resulting in an intracellular and extracellular elevation of IL6 protein, which was accompanied by a reduced expression of tight and adherens junctions, claudin-5, occludin, and vascular-endothelial (VE-) cadherin. By functional assays, we could demonstrate IL6-incubated brain ECs to lose their endothelial integrity that can be attenuated by inhibiting the IL6R. Blockade of the IL6R by a neutralizing antibody has reconstituted the intercellular junction expression to the control level and caused a restoration of the transendothelial electrical resistance of the cEND cell monolayer. Our findings add depth to the current understanding of the involvement of the endothelial IL6R in the loss of EC integrity implicating potential therapy options.

[Evolution of human brain and intelligence].

Science.gov (United States)

Lakatos, László; Janka, Zoltán

2008-07-30

The biological evolution, including human evolution is mainly driven by environmental changes. Accidental genetic modifications and their innovative results make the successful adaptation possible. As we know the human evolution started 7-8 million years ago in the African savannah, where upright position and bipedalism were significantly advantageous. The main drive of improving manual actions and tool making could be to obtain more food. Our ancestor got more meat due to more successful hunting, resulting in more caloric intake, more protein and essential fatty acid in the meal. The nervous system uses disproportionally high level of energy, so better quality of food was a basic condition for the evolution of huge human brain. The size of human brain was tripled during 3.5 million years, it increased from the average of 450 cm3 of Australopithecinae to the average of 1350 cm3 of Homo sapiens. A genetic change in the system controlling gene expression could happen about 200 000 years ago, which influenced the development of nervous system, the sensorimotor function and learning ability for motor processes. The appearance and stabilisation of FOXP2 gene structure as feature of modern man coincided with the first presence and quick spread of Homo sapiens on the whole Earth. This genetic modification made opportunity for human language, as the basis of abrupt evolution of human intelligence. The brain region being responsible for human language is the left planum temporale, which is much larger in left hemisphere. This shows the most typical human brain asymmetry. In this case the anatomical asymmetry means a clearly defined functional asymmetry as well, where the brain hemispheres act differently. The preference in using hands, the lateralised using of tools resulted in the brain asymmetry, which is the precondition of human language and intelligence. However, it cannot be held anymore, that only humans make tools, because our closest relatives, the chimpanzees are

Graft microvascular disease in solid organ transplantation.

Science.gov (United States)

Jiang, Xinguo; Sung, Yon K; Tian, Wen; Qian, Jin; Semenza, Gregg L; Nicolls, Mark R

2014-08-01

Alloimmune inflammation damages the microvasculature of solid organ transplants during acute rejection. Although immunosuppressive drugs diminish the inflammatory response, they do not directly promote vascular repair. Repetitive microvascular injury with insufficient regeneration results in prolonged tissue hypoxia and fibrotic remodeling. While clinical studies show that a loss of the microvascular circulation precedes and may act as an initiating factor for the development of chronic rejection, preclinical studies demonstrate that improved microvascular perfusion during acute rejection delays and attenuates tissue fibrosis. Therefore, preservation of a functional microvasculature may represent an effective therapeutic strategy for preventing chronic rejection. Here, we review recent advances in our understanding of the role of the microvasculature in the long-term survival of transplanted solid organs. We also highlight microvessel-centered therapeutic strategies for prolonging the survival of solid organ transplants.

Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells

Energy Technology Data Exchange (ETDEWEB)

Zhan, J. [Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei (China); Xiao, F. [Department of Osteology, Pu Ai Hospital, Huazhong University of Science and Technology, Wuhan, Hubei (China); Zhang, Z.Z.; Wang, Y.P.; Chen, K.; Wang, Y.L. [Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei (China)

2013-12-02

β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M{sub 3} receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury.

Effect of penehyclidine hydrochloride on β-arrestin-1 expression in lipopolysaccharide-induced human pulmonary microvascular endothelial cells

International Nuclear Information System (INIS)

Zhan, J.; Xiao, F.; Zhang, Z.Z.; Wang, Y.P.; Chen, K.; Wang, Y.L.

2013-01-01

β-arrestins are expressed proteins that were first described, and are well-known, as negative regulators of G protein-coupled receptor signaling. Penehyclidine hydrochloride (PHC) is a new anti-cholinergic drug that can inhibit biomembrane lipid peroxidation, and decrease cytokines and oxyradicals. However, to date, no reports on the effects of PHC on β-arrestin-1 in cells have been published. The aim of this study was to investigate the effect of PHC on β-arrestin-1 expression in lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMEC). Cultured HPMEC were pretreated with PHC, followed by LPS treatment. Muscarinic receptor mRNAs were assayed by real-time quantitative PCR. Cell viability was assayed by the methyl thiazolyl tetrazolium (MTT) conversion test. The dose and time effects of PHC on β-arrestin-1 expression in LPS-induced HPMEC were determined by Western blot analysis. Cell malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured. It was found that the M 3 receptor was the one most highly expressed, and was activated 5 min after LPS challenge. Furthermore, 2 μg/mL PHC significantly upregulated expression of β-arrestin-1 within 10 to 15 min. Compared with the control group, MDA levels in cells were remarkably increased and SOD activities were significantly decreased in LPS pretreated cells, while PHC markedly decreased MDA levels and increased SOD activities. We conclude that PHC attenuated ROS injury by upregulating β-arrestin-1 expression, thereby implicating a mechanism by which PHC may exert its protective effects against LPS-induced pulmonary microvascular endothelial cell injury

The evolution of modern human brain shape

Science.gov (United States)

Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp

2018-01-01

Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils (N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity. PMID:29376123

The evolution of modern human brain shape.

Science.gov (United States)

Neubauer, Simon; Hublin, Jean-Jacques; Gunz, Philipp

2018-01-01

Modern humans have large and globular brains that distinguish them from their extinct Homo relatives. The characteristic globularity develops during a prenatal and early postnatal period of rapid brain growth critical for neural wiring and cognitive development. However, it remains unknown when and how brain globularity evolved and how it relates to evolutionary brain size increase. On the basis of computed tomographic scans and geometric morphometric analyses, we analyzed endocranial casts of Homo sapiens fossils ( N = 20) from different time periods. Our data show that, 300,000 years ago, brain size in early H. sapiens already fell within the range of present-day humans. Brain shape, however, evolved gradually within the H. sapiens lineage, reaching present-day human variation between about 100,000 and 35,000 years ago. This process started only after other key features of craniofacial morphology appeared modern and paralleled the emergence of behavioral modernity as seen from the archeological record. Our findings are consistent with important genetic changes affecting early brain development within the H. sapiens lineage since the origin of the species and before the transition to the Later Stone Age and the Upper Paleolithic that mark full behavioral modernity.

Reduction in cardiolipin decreases mitochondrial spare respiratory capacity and increases glucose transport into and across human brain cerebral microvascular endothelial cells.

Science.gov (United States)

Nguyen, Hieu M; Mejia, Edgard M; Chang, Wenguang; Wang, Ying; Watson, Emily; On, Ngoc; Miller, Donald W; Hatch, Grant M

2016-10-01

Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. Cardiolipin is a mitochondrial phospholipid required for function of the electron transport chain and ATP generation. We examined the role of cardiolipin in maintaining mitochondrial function necessary to support barrier properties of brain microvessel endothelial cells. Knockdown of the terminal enzyme of cardiolipin synthesis, cardiolipin synthase, in hCMEC/D3 cells resulted in decreased cellular cardiolipin levels compared to controls. The reduction in cardiolipin resulted in decreased mitochondrial spare respiratory capacity, increased pyruvate kinase activity, and increased 2-deoxy-[(3) H]glucose uptake and glucose transporter-1 expression and localization to membranes in hCMEC/D3 cells compared to controls. The mechanism for the increase in glucose uptake was an increase in adenosine-5'-monophosphate kinase and protein kinase B activity and decreased glycogen synthase kinase 3 beta activity. Knockdown of cardiolipin synthase did not affect permeability of fluorescent dextran across confluent hCMEC/D3 monolayers grown on Transwell(®) inserts. In contrast, knockdown of cardiolipin synthase resulted in an increase in 2-deoxy-[(3) H]glucose transport across these monolayers compared to controls. The data indicate that in hCMEC/D3 cells, spare respiratory capacity is dependent on cardiolipin. In addition, reduction in cardiolipin in these cells alters their cellular energy status and this results in increased glucose transport into and across hCMEC/D3 monolayers. Microvessel endothelial cells form part of the blood-brain barrier, a restrictively permeable interface that allows transport of only specific compounds into the brain. In human adult brain endothelial cell hCMEC/D3 monolayers cultured on Transwell(®) plates, knockdown of cardiolipin synthase results in decrease in mitochondrial

Apolipoprotein B level and diabetic microvascular complications ( is there a correlation?

Directory of Open Access Journals (Sweden)

Mary N. Rizk

2013-01-01

Conclusion Apo B levels are strongly correlated to diabetic microvascular complications. The higher the degree of nephropathy, the higher the Apo B level. The presence of more than one microvascular complication correlates positively with high levels of Apo B. This suggests the possible use of Apo B as a sensitive biomarker of the presence of early diabetic microvascular complications.

Plasmalemmal Vesicle Associated Protein-1 (PV-1 is a marker of blood-brain barrier disruption in rodent models

Directory of Open Access Journals (Sweden)

Ali Zarina S

2008-02-01

Full Text Available Abstract Background Plasmalemmal vesicle associated protein-1 (PV-1 is selectively expressed in human brain microvascular endothelial cells derived from clinical specimens of primary and secondary malignant brain tumors, cerebral ischemia, and other central nervous system (CNS diseases associated with blood-brain barrier breakdown. In this study, we characterize the murine CNS expression pattern of PV-1 to determine whether localized PV-1 induction is conserved across species and disease state. Results We demonstrate that PV-1 is selectively upregulated in mouse blood vessels recruited by brain tumor xenografts at the RNA and protein levels, but is not detected in non-neoplastic brain. Additionally, PV-1 is induced in a mouse model of acute ischemia. Expression is confined to the cerebovasculature within the region of infarct and is temporally regulated. Conclusion Our results confirm that PV-1 is preferentially induced in the endothelium of mouse brain tumors and acute ischemic brain tissue and corresponds to blood-brain barrier disruption in a fashion analogous to human patients. Characterization of PV-1 expression in mouse brain is the first step towards development of rodent models for testing anti-edema and anti-angiogenesis therapeutic strategies based on this molecule.

A human-specific de novo protein-coding gene associated with human brain functions.

Directory of Open Access Journals (Sweden)

Chuan-Yun Li

2010-03-01

Full Text Available To understand whether any human-specific new genes may be associated with human brain functions, we computationally screened the genetic vulnerable factors identified through Genome-Wide Association Studies and linkage analyses of nicotine addiction and found one human-specific de novo protein-coding gene, FLJ33706 (alternative gene symbol C20orf203. Cross-species analysis revealed interesting evolutionary paths of how this gene had originated from noncoding DNA sequences: insertion of repeat elements especially Alu contributed to the formation of the first coding exon and six standard splice junctions on the branch leading to humans and chimpanzees, and two subsequent substitutions in the human lineage escaped two stop codons and created an open reading frame of 194 amino acids. We experimentally verified FLJ33706's mRNA and protein expression in the brain. Real-Time PCR in multiple tissues demonstrated that FLJ33706 was most abundantly expressed in brain. Human polymorphism data suggested that FLJ33706 encodes a protein under purifying selection. A specifically designed antibody detected its protein expression across human cortex, cerebellum and midbrain. Immunohistochemistry study in normal human brain cortex revealed the localization of FLJ33706 protein in neurons. Elevated expressions of FLJ33706 were detected in Alzheimer's brain samples, suggesting the role of this novel gene in human-specific pathogenesis of Alzheimer's disease. FLJ33706 provided the strongest evidence so far that human-specific de novo genes can have protein-coding potential and differential protein expression, and be involved in human brain functions.

Vascular endothelial growth factor is upregulated by l-dopa in the parkinsonian brain: implications for the development of dyskinesia

Science.gov (United States)

Francardo, Veronica; Lindgren, Hanna S.; Sillivan, Stephanie E.; O’Sullivan, Sean S.; Luksik, Andrew S.; Vassoler, Fair M.; Lees, Andrew J.; Konradi, Christine

2011-01-01

Angiogenesis and increased permeability of the blood–brain barrier have been reported to occur in animal models of Parkinson’s disease and l-dopa-induced dyskinesia, but the significance of these phenomena has remained unclear. Using a validated rat model of l-dopa-induced dyskinesia, this study demonstrates that chronic treatment with l-dopa dose dependently induces the expression of vascular endothelial growth factor in the basal ganglia nuclei. Vascular endothelial growth factor was abundantly expressed in astrocytes and astrocytic processes in the proximity of blood vessels. When co-administered with l-dopa, a small molecule inhibitor of vascular endothelial growth factor signalling significantly attenuated the development of dyskinesia and completely blocked the angiogenic response and associated increase in blood–brain barrier permeability induced by the treatment. The occurrence of angiogenesis and vascular endothelial growth factor upregulation was verified in post-mortem basal ganglia tissue from patients with Parkinson’s disease with a history of dyskinesia, who exhibited increased microvascular density, microvascular nestin expression and an upregulation of vascular endothelial growth factor messenger ribonucleic acid. These congruent findings in the rat model and human patients indicate that vascular endothelial growth factor is implicated in the pathophysiology of l-dopa-induced dyskinesia and emphasize an involvement of the microvascular compartment in the adverse effects of l-dopa pharmacotherapy in Parkinson’s disease. PMID:21771855

Macroscopic networks in the human brain: mapping connectivity in healthy and damaged brains

NARCIS (Netherlands)

Nijhuis, E.H.J.

2013-01-01

The human brain contains a network of interconnected neurons. Recent advances in functional and structural in-vivo magnetic resonance neuroimaging (MRI) techniques have provided opportunities to model the networks of the human brain on a macroscopic scale. This dissertation investigates the

Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications.

Science.gov (United States)

Fortunato, Tiago M; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A; Pula, Giordano

2016-05-04

Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs.

Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer.

Directory of Open Access Journals (Sweden)

Nina P Connolly

Full Text Available Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS virus / tumor virus receptor-A (tv-a transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor

Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage.

Science.gov (United States)

Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf; Edvinsson, Lars

2015-01-01

Migraine is a paroxysmal, disabling primary headache that affects 16 % of the adult population. In spite of decades of intense research, the origin and the pathophysiology mechanisms involved are still not fully known. Although triptans and gepants provide effective relief from acute migraine for many patients, their site of action remains unidentified. It has been suggested that during migraine attacks the leakiness of the blood-brain barrier (BBB) is altered, increasing the passage of anti-migraine drugs. This study aimed to investigate the effect of experimental inflammation, following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface. Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG is readily exposed to circulating molecules. The TG could provide a site of anti-migraine drug interaction with effect on the trigeminal system.

Functional organization of the transcriptome in human brain

Science.gov (United States)

Oldham, Michael C; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H

2009-01-01

The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain’s transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type–specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome. PMID:18849986

Lipidomics of human brain aging and Alzheimer's disease pathology.

Science.gov (United States)

Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

2015-01-01

Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

Lipid transport and human brain development.

Science.gov (United States)

Betsholtz, Christer

2015-07-01

How the human brain rapidly builds up its lipid content during brain growth and maintains its lipids in adulthood has remained elusive. Two new studies show that inactivating mutations in MFSD2A, known to be expressed specifically at the blood-brain barrier, lead to microcephaly, thereby offering a simple and surprising solution to an old enigma.

Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

Science.gov (United States)

Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

2009-07-01

We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo.

Neuroglobin and Cytoglobin expression in the human brain

DEFF Research Database (Denmark)

Hundahl, Christian Ansgar; Kelsen, Jesper; Hay-Schmidt, Anders

2013-01-01

Neuroglobin and Cytoglobin are new members of the heme-globin family. Both globins are primarily expressed in neurons of the brain and retina. Neuroglobin and Cytoglobin have been suggested as novel therapeutic targets in various neurodegenerative diseases based on their oxygen binding and cell...... protecting properties. However, findings in Neuroglobin-deficient mice question the endogenous neuroprotective properties. The expression pattern of Neuroglobin and Cytoglobin in the rodent brain is also in contradiction to a major role of neuronal protection. In a recent study, Neuroglobin was ubiquitously...... expressed and up-regulated following stroke in the human brain. The present study aimed at confirming our previous observations in rodents using two post-mortem human brains. The anatomical localization of Neuroglobin and Cytoglobin in the human brain is much like what has been described for the rodent...

Sleep Restriction Impairs Blood–Brain Barrier Function

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He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J.; Wang, Yuping

2014-01-01

The blood–brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. PMID:25355222

Sex beyond the genitalia: The human brain mosaic

Science.gov (United States)

Joel, Daphna; Berman, Zohar; Tavor, Ido; Wexler, Nadav; Gaber, Olga; Stein, Yaniv; Shefi, Nisan; Pool, Jared; Urchs, Sebastian; Margulies, Daniel S.; Liem, Franziskus; Hänggi, Jürgen; Jäncke, Lutz; Assaf, Yaniv

2015-01-01

Whereas a categorical difference in the genitals has always been acknowledged, the question of how far these categories extend into human biology is still not resolved. Documented sex/gender differences in the brain are often taken as support of a sexually dimorphic view of human brains (“female brain” or “male brain”). However, such a distinction would be possible only if sex/gender differences in brain features were highly dimorphic (i.e., little overlap between the forms of these features in males and females) and internally consistent (i.e., a brain has only “male” or only “female” features). Here, analysis of MRIs of more than 1,400 human brains from four datasets reveals extensive overlap between the distributions of females and males for all gray matter, white matter, and connections assessed. Moreover, analyses of internal consistency reveal that brains with features that are consistently at one end of the “maleness-femaleness” continuum are rare. Rather, most brains are comprised of unique “mosaics” of features, some more common in females compared with males, some more common in males compared with females, and some common in both females and males. Our findings are robust across sample, age, type of MRI, and method of analysis. These findings are corroborated by a similar analysis of personality traits, attitudes, interests, and behaviors of more than 5,500 individuals, which reveals that internal consistency is extremely rare. Our study demonstrates that, although there are sex/gender differences in the brain, human brains do not belong to one of two distinct categories: male brain/female brain. PMID:26621705

[Recent advances on pericytes in microvascular dysfunction and traditional Chinese medicine prevention].

Science.gov (United States)

Liu, Lei; Liu, Jian-Xun; Guo, Hao; Ren, Jian-Xun

2017-08-01

Pericytesis a kind of widespread vascular mural cells embedded within the vascular basement membrane of blood microvessels, constituting the barrier of capillaries and tissue spaces together with endothelial cells. Pericytes communicate with microvascular endothelial cells through cell connections or paracrine signals, playing an important role in important physiological processes such as blood flow, vascular permeability and vascular formation. Pericytes dysfunction may participate in some microvascular dysfunction, and also mediate pathological repair process, therefore pericytes attracted more and more attention. Traditional Chinese medicine suggests that microvascular dysfunction belongs to the collaterals disease; Qi stagnation and blood stasis in collaterals result in function imbalance of internal organs. Traditional Chinese medicine (TCM) has shown effects on pericytes in microvascular dysfunction, for example qi reinforcing blood-circulation activating medicines can reduce the damage of retinal pericytes in diabetic retinopathy. However, there are some limitations of research fields, inaccuracy of research techniques and methods, and lack of mechanism elaboration depth in the study of microvascular lesion pericytes. This paper reviewed the biological characteristics of pericytes and pericytes in microvascular dysfunction, as well as the intervention study of TCM on pericytes. The article aims to provide reference for the research of pericytes in microvascular dysfunction and the TCM study on pericytes. Copyright© by the Chinese Pharmaceutical Association.

An introduction to human brain anatomy

NARCIS (Netherlands)

Forstmann, B.U.; Keuken, M.C.; Alkemade, A.; Forstmann, B.U.; Wagenmakers, E.-J.

2015-01-01

This tutorial chapter provides an overview of the human brain anatomy. Knowledge of brain anatomy is fundamental to our understanding of cognitive processes in health and disease; moreover, anatomical constraints are vital for neurocomputational models and can be important for psychological

Analysis of a human brain transcriptome map

Directory of Open Access Journals (Sweden)

Greene Jonathan R

2002-04-01

Full Text Available Abstract Background Genome wide transcriptome maps can provide tools to identify candidate genes that are over-expressed or silenced in certain disease tissue and increase our understanding of the structure and organization of the genome. Expressed Sequence Tags (ESTs from the public dbEST and proprietary Incyte LifeSeq databases were used to derive a transcript map in conjunction with the working draft assembly of the human genome sequence. Results Examination of ESTs derived from brain tissues (excluding brain tumor tissues suggests that these genes are distributed on chromosomes in a non-random fashion. Some regions on the genome are dense with brain-enriched genes while some regions lack brain-enriched genes, suggesting a significant correlation between distribution of genes along the chromosome and tissue type. ESTs from brain tumor tissues have also been mapped to the human genome working draft. We reveal that some regions enriched in brain genes show a significant decrease in gene expression in brain tumors, and, conversely that some regions lacking in brain genes show an increased level of gene expression in brain tumors. Conclusions This report demonstrates a novel approach for tissue specific transcriptome mapping using EST-based quantitative assessment.

The application of microfocal radiography to neuroanatomy and neuropathology research, and its relation to cerebral magnification angiography and brain scan interpretation. Chapter 3

International Nuclear Information System (INIS)

Saunders, R.L. de C.H.

1980-01-01

Microfocal radiography is used to study post mortem, the microcirculatory and neuronal organization of the normal and diseased brain, as well as to interpret the images obtained clinically by the new techniques of cerebral magnification angiography and X-ray brain scanning. An outline of the basic technique underlying CT scanning and magnification radiography of the living human brain is given to facilitate the understanding of why microfocal radiography is central to magnification radiography and complementary to CT scanning. Microangiography, one of the microfocal radiographic techniques, is discussed at length in relation to the microvasculature of the human cerebral cortex, the vasculature of the subcortical or medullary white matter, the microvascular patterns of the central grey matter and internal capsule, the vascular patterns of the visual cortex and hippocampus; the application of microangiography to the spinal cord and nerve roots is also discussed. Another microfocal radiographic technique described is cerebral historadiography, i.e. X-ray studies of brain histology, with particular reference to the human hippocampal formation. Finally, the correlation of microfocal X-ray and brain CT scan images is discussed. (U.K.)

Small-world human brain networks: Perspectives and challenges.

Science.gov (United States)

Liao, Xuhong; Vasilakos, Athanasios V; He, Yong

2017-06-01

Modelling the human brain as a complex network has provided a powerful mathematical framework to characterize the structural and functional architectures of the brain. In the past decade, the combination of non-invasive neuroimaging techniques and graph theoretical approaches enable us to map human structural and functional connectivity patterns (i.e., connectome) at the macroscopic level. One of the most influential findings is that human brain networks exhibit prominent small-world organization. Such a network architecture in the human brain facilitates efficient information segregation and integration at low wiring and energy costs, which presumably results from natural selection under the pressure of a cost-efficiency balance. Moreover, the small-world organization undergoes continuous changes during normal development and ageing and exhibits dramatic alterations in neurological and psychiatric disorders. In this review, we survey recent advances regarding the small-world architecture in human brain networks and highlight the potential implications and applications in multidisciplinary fields, including cognitive neuroscience, medicine and engineering. Finally, we highlight several challenging issues and areas for future research in this rapidly growing field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Zebrafish as a Model for the Study of Microvascular Complications of Diabetes and Their Mechanisms

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Karl Heckler

2017-09-01

Full Text Available Diabetes mellitus (DM is a crucial metabolic disease that leads to severe disorders. These include macrovascular complications such as myocardial infarction, stroke, and peripheral artery disease and microvascular complications including diabetic nephropathy, neuropathy, and retinopathy. Diabetes mellitus, along with its associated organ pathologies, is one of the key problems in today’s medicine. Zebrafish is an upcoming disease model organism in diabetes research. Its glucose metabolism and the pathways of reactive metabolite formation are very similar to those of humans. Moreover, several physiological and pathophysiological pathways that also exist in humans and other mammals have been identified in this species or are currently under intense investigation. Zebrafish offer sophisticated imaging techniques and allow simple and fast genetic and pharmacological approaches with a high throughput. In this review, we highlight achievements and mechanisms concerning microvascular complications discovered in zebrafish, and we discuss the advantages and disadvantages of zebrafish as a model for studying diabetic complications.

Peripheral Microvascular Responses to Whole-Body Tilting, G(z) Centrifugation, and Lower Body Negative Pressure Stresses in Humans

Science.gov (United States)

Breit, G. A.; Watenpaugh, D. E.; Buckley, T. M.; Ballard, R. E.; Murthy, G.; Hargens, A. R.

1994-01-01

The response of the cutaneous microcirculation to orthostatic stress varies along the length of the body due to the interaction of central controls with regional responses to local blood pressure. We hypothesize that artificial orthostatic stresses such as Gz centrifugation and LBNP differ from whole-body tilting in terms of the distribution of microvascular blood flow. Cutaneous microvascular flows were measured by laser Doppler flowmetry at the neck, thigh, and leg of 15 normal subjects. Volunteers underwent stepwise head-up tilt (HUT) and short- and long-arm centrifugation protocols from supine control (0 Gz) to 0.2, 0.4, 0.6, 0.8, 1.0, 0.8, 0.6, 0.4, 0.2, and 0 Gz at the feet, for 30-s periods with 10-s transitions between levels. The same subjects underwent a corresponding supine LBNP protocol, up to 100 mmHg (in 20 mmHg increments) and back to zero pressure, which produced transmural pressure across blood vessels in the foot approximately equal to the HUT protocol. In general, application of all orthostatic stresses produced significant flow reductions in the lower body (p less than 0.05) and inconsistent changes in the neck. At low levels of each stress (0.4 Gz, 40 mmHg), LBNP generated the greatest relative reduction in flow in the lower body (-66.9+/-5.7%, thigh; -60.6 +/-5.7%, leg, mean +/- SE). HUT caused a less severe flow reduction than LBNP at the thigh and leg (-39.9 +/- 8.1% and -55.9+/-4.8%), while the effects induced by both forms of centrifugation were the least profound. Higher levels of each stress generally resulted in similar responses. These responses exhibit a consistent relationship to hypothesized changes in local microvascular transmural pressure, suggesting that myogenic and veno-arteriolar reflexes play a significant role in determining microvascular perfusion during orthostatic stress.

Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

Institute of Scientific and Technical Information of China (English)

HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

2004-01-01

Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

Astrocyte calcium signal and gliotransmission in human brain tissue.

Science.gov (United States)

Navarrete, Marta; Perea, Gertrudis; Maglio, Laura; Pastor, Jesús; García de Sola, Rafael; Araque, Alfonso

2013-05-01

Brain function is recognized to rely on neuronal activity and signaling processes between neurons, whereas astrocytes are generally considered to play supportive roles for proper neuronal function. However, accumulating evidence indicates that astrocytes sense and control neuronal and synaptic activity, indicating that neuron and astrocytes reciprocally communicate. While this evidence has been obtained in experimental animal models, whether this bidirectional signaling between astrocytes and neurons occurs in human brain remains unknown. We have investigated the existence of astrocyte-neuron communication in human brain tissue, using electrophysiological and Ca(2+) imaging techniques in slices of the cortex and hippocampus obtained from biopsies from epileptic patients. Cortical and hippocampal human astrocytes displayed spontaneous Ca(2+) elevations that were independent of neuronal activity. Local application of transmitter receptor agonists or nerve electrical stimulation transiently elevated Ca(2+) in astrocytes, indicating that human astrocytes detect synaptic activity and respond to synaptically released neurotransmitters, suggesting the existence of neuron-to-astrocyte communication in human brain tissue. Electrophysiological recordings in neurons revealed the presence of slow inward currents (SICs) mediated by NMDA receptor activation. The frequency of SICs increased after local application of ATP that elevated astrocyte Ca(2+). Therefore, human astrocytes are able to release the gliotransmitter glutamate, which affect neuronal excitability through activation of NMDA receptors in neurons. These results reveal the existence of reciprocal signaling between neurons and astrocytes in human brain tissue, indicating that astrocytes are relevant in human neurophysiology and are involved in human brain function.

Tumor microvascular changes in antiangiogenic treatment : Assessment by magnetic resonance contrast media of different molecular weights

NARCIS (Netherlands)

Turetschek, K; Preda, A; Novikov, [No Value; Brasch, RC; Weinmann, HJ; Wunderbaldinger, P; Roberts, TPL

Purpose: To test magnetic resonance (MR) contrast media of different molecular weights (MWs) for their potential to characterize noninvasively microvascular changes in an experimental tumor treatment model. Materials and Methods: MD-MBA-435, a poorly differentiated human breast cancer cell line, was

Do glutathione levels decline in aging human brain?

Science.gov (United States)

Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

2016-04-01

For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

Multilayer modeling and analysis of human brain networks

Science.gov (United States)

2017-01-01

Abstract Understanding how the human brain is structured, and how its architecture is related to function, is of paramount importance for a variety of applications, including but not limited to new ways to prevent, deal with, and cure brain diseases, such as Alzheimer’s or Parkinson’s, and psychiatric disorders, such as schizophrenia. The recent advances in structural and functional neuroimaging, together with the increasing attitude toward interdisciplinary approaches involving computer science, mathematics, and physics, are fostering interesting results from computational neuroscience that are quite often based on the analysis of complex network representation of the human brain. In recent years, this representation experienced a theoretical and computational revolution that is breaching neuroscience, allowing us to cope with the increasing complexity of the human brain across multiple scales and in multiple dimensions and to model structural and functional connectivity from new perspectives, often combined with each other. In this work, we will review the main achievements obtained from interdisciplinary research based on magnetic resonance imaging and establish de facto, the birth of multilayer network analysis and modeling of the human brain. PMID:28327916

HIF-2α Expression Regulates Sprout Formation into 3D Fibrin Matrices in Prolonged Hypoxia in Human Microvascular Endothelial Cells.

Science.gov (United States)

Nauta, Tessa D; Duyndam, Monique C A; Weijers, Ester M; van Hinsbergh, Victor M W; Koolwijk, Pieter

2016-01-01

During short-term hypoxia, Hypoxia Inducible Factors (particular their subunits HIF-1α and HIF-2α) regulate the expression of many genes including the potent angiogenesis stimulator VEGF. However, in some pathological conditions chronic hypoxia occurs and is accompanied by reduced angiogenesis. We investigated the effect of prolonged hypoxia on the proliferation and sprouting ability of human microvascular endothelial cells and the involvement of the HIFs and Dll4/Notch signaling. Human microvascular endothelial cells (hMVECs), cultured at 20% oxygen for 14 days and seeded on top of 3D fibrin matrices, formed sprouts when stimulated with VEGF-A/TNFα. In contrast, hMVECs precultured at 1% oxygen for 14 days were viable and proliferative, but did not form sprouts into fibrin upon VEGF-A/TNFα stimulation at 1% oxygen. Silencing of HIF-2α with si-RNA partially restored the inhibition of endothelial sprouting, whereas HIF-1α or HIF-3α by si-RNA had no effect. No involvement of Dll4/Notch pathway in the inhibitory effect on endothelial sprouting by prolonged hypoxia was found. In addition, hypoxia decreased the production of urokinase-type plasminogen activator (uPA), needed for migration and invasion, without a significant effect on its inhibitor PAI-1. This was independent of HIF-2α, as si-HIF-2α did not counteract uPA reduction. Prolonged culturing of hMVECs at 1% oxygen inhibited endothelial sprouting into fibrin. Two independent mechanisms contribute. Silencing of HIF-2α with si-RNA partially restored the inhibition of endothelial sprouting pointing to a HIF-2α-dependent mechanism. In addition, reduction of uPA contributed to reduced endothelial tube formation in a fibrin matrix during prolonged hypoxia.

Revisiting Glycogen Content in the Human Brain.

Science.gov (United States)

Öz, Gülin; DiNuzzo, Mauro; Kumar, Anjali; Moheet, Amir; Seaquist, Elizabeth R

2015-12-01

Glycogen provides an important glucose reservoir in the brain since the concentration of glucosyl units stored in glycogen is several fold higher than free glucose available in brain tissue. We have previously reported 3-4 µmol/g brain glycogen content using in vivo (13)C magnetic resonance spectroscopy (MRS) in conjunction with [1-(13)C]glucose administration in healthy humans, while higher levels were reported in the rodent brain. Due to the slow turnover of bulk brain glycogen in humans, complete turnover of the glycogen pool, estimated to take 3-5 days, was not observed in these prior studies. In an attempt to reach complete turnover and thereby steady state (13)C labeling in glycogen, here we administered [1-(13)C]glucose to healthy volunteers for 80 h. To eliminate any net glycogen synthesis during this period and thereby achieve an accurate estimate of glycogen concentration, volunteers were maintained at euglycemic blood glucose levels during [1-(13)C]glucose administration and (13)C-glycogen levels in the occipital lobe were measured by (13)C MRS approximately every 12 h. Finally, we fitted the data with a biophysical model that was recently developed to take into account the tiered structure of the glycogen molecule and additionally incorporated blood glucose levels and isotopic enrichments as input function in the model. We obtained excellent fits of the model to the (13)C-glycogen data, and glycogen content in the healthy human brain tissue was found to be 7.8 ± 0.3 µmol/g, a value substantially higher than previous estimates of glycogen content in the human brain.

Hydrogen-Rich Saline Attenuates Brain Injury Induced by Cardiopulmonary Bypass and Inhibits Microvascular Endothelial Cell Apoptosis Via the PI3K/Akt/GSK3β Signaling Pathway in Rats

Directory of Open Access Journals (Sweden)

Keyan Chen

2017-10-01

Full Text Available Background/Aims: Cardiopulmonary bypass (CPB is prone to inducing brain injury during open heart surgery. A hydrogen-rich solution (HRS can prevent oxidation and apoptosis, and inhibit inflammation. This study investigated effects of HRS on brain injury induced by CPB and regulatory mechanisms of the PI3K/Akt/GSK3β signaling pathway. Methods: A rat CPB model and an in vitro cell hypoxia model were established. After HRS treatment, Rat behavior was measured using neurological deficit score; Evans blue (EB was used to assess permeability of the blood-brain barrier (BBB; HE staining was used to observe pathological changes; Inflammatory factors and brain injury markers were detected by ELISA; the PI3K/Akt/GSK3β pathway-related proteins and apoptosis were assessed by western blot, immunohistochemistry and qRT –PCR analyses of brain tissue and neurons. Results: After CPB, brain tissue anatomy was disordered, and cell structure was abnormal. Brain tissue EB content increased. There was an increase in the number of apoptotic cells, an increase in expression of Bax and caspase-3, a decrease in expression of Bcl2, and increases in levels of Akt, GSK3β, P-Akt, and P-GSK3β in brain tissue. HRS treatment attenuated the inflammatory reaction ,brain tissue EB content was significantly reduced and significantly decreased expression levels of Bax, caspase-3, Akt, GSK3β, P-Akt, and P-GSK3β in the brain. After adding the PI3K signaling pathway inhibitor, LY294002, to rat cerebral microvascular endothelial cells (CMECs, HRS could reduce activated Akt expression and downstream regulatory gene phosphorylation of GSK3β expression, and inhibit CMEC apoptosis. Conclusion: The PI3K/Akt/GSK3β signaling pathway plays an important role in the mechanism of CPB-induced brain injury. HRS can reduce CPB-induced brain injury and inhibit CMEC apoptosis through the PI3K/Akt/GSK3β signaling pathway.

Epigalloccatechin-3-gallate Inhibits Ocular Neovascularization and Vascular Permeability in Human Retinal Pigment Epithelial and Human Retinal Microvascular Endothelial Cells via Suppression of MMP-9 and VEGF Activation

Directory of Open Access Journals (Sweden)

Hak Sung Lee

2014-08-01

Full Text Available Epigalloccatechin-3-gallate (EGCG is the main polyphenol component of green tea (leaves of Camellia sinensis. EGCG is known for its antioxidant, anti-inflammatory, antiviral, and anti-carcinogenic properties. Here, we identify EGCG as a new inhibitor of ocular angiogenesis and its vascular permeability. Matrix metalloproteinases (MMPs and vascular endothelial growth factor (VEGF play a key role in the processes of extracellular matrix (ECM remodeling and microvascular permeability during angiogenesis. We investigated the inhibitory effects of EGCG on ocular neovascularization and vascular permeability using the retina oriented cells and animal models induced by VEGF and alkaline burn. EGCG treatment significantly decreased mRNA and protein expression levels of MMP-9 in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA and tumor necrosis factor alpha (TNF-α in human retinal pigment epithelial cells (HRPECs. EGCG also effectively protected ARPE-19 cells from cell death and attenuated mRNA expressions of key angiogenic factors (MMP-9, VEGF, VEGF Receptor-2 by inhibiting generation of reactive oxygen species (ROS. EGCG significantly inhibited proliferation, vascular permeability, and tube formation in VEGF-induced human retinal microvascular endothelial cells (HRMECs. Furthermore, EGCG significantly reduced vascular leakage and permeability by blood-retinal barrier breakdown in VEGF-induced animal models. In addition, EGCG effectively limited upregulation of MMP-9 and platelet endothelial cell adhesion molecule (PECAM/CD31 on corneal neovascularization (CNV induced by alkaline burn. Our data suggest that MMP-9 and VEGF are key therapeutic targets of EGCG for treatment and prevention of ocular angiogenic diseases such as age-related macular degeneration, diabetic retinopathy, and corneal neovascularization.

Brain shape in human microcephalics and Homo floresiensis.

Science.gov (United States)

Falk, Dean; Hildebolt, Charles; Smith, Kirk; Morwood, M J; Sutikna, Thomas; Jatmiko; Saptomo, E Wayhu; Imhof, Herwig; Seidler, Horst; Prior, Fred

2007-02-13

Because the cranial capacity of LB1 (Homo floresiensis) is only 417 cm(3), some workers propose that it represents a microcephalic Homo sapiens rather than a new species. This hypothesis is difficult to assess, however, without a clear understanding of how brain shape of microcephalics compares with that of normal humans. We compare three-dimensional computed tomographic reconstructions of the internal braincases (virtual endocasts that reproduce details of external brain morphology, including cranial capacities and shape) from a sample of 9 microcephalic humans and 10 normal humans. Discriminant and canonical analyses are used to identify two variables that classify normal and microcephalic humans with 100% success. The classification functions classify the virtual endocast from LB1 with normal humans rather than microcephalics. On the other hand, our classification functions classify a pathological H. sapiens specimen that, like LB1, represents an approximately 3-foot-tall adult female and an adult Basuto microcephalic woman that is alleged to have an endocast similar to LB1's with the microcephalic humans. Although microcephaly is genetically and clinically variable, virtual endocasts from our highly heterogeneous sample share similarities in protruding and proportionately large cerebella and relatively narrow, flattened orbital surfaces compared with normal humans. These findings have relevance for hypotheses regarding the genetic substrates of hominin brain evolution and may have medical diagnostic value. Despite LB1's having brain shape features that sort it with normal humans rather than microcephalics, other shape features and its small brain size are consistent with its assignment to a separate species.

Human brain networks function in connectome-specific harmonic waves.

Science.gov (United States)

Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

2016-01-21

A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call 'connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory-inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation-inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness.

Palmitate-induced inflammatory pathways in human adipose microvascular endothelial cells promote monocyte adhesion and impair insulin transcytosis.

Science.gov (United States)

Pillon, Nicolas J; Azizi, Paymon M; Li, Yujin E; Liu, Jun; Wang, Changsen; Chan, Kenny L; Hopperton, Kathryn E; Bazinet, Richard P; Heit, Bryan; Bilan, Philip J; Lee, Warren L; Klip, Amira

2015-07-01

Obesity is associated with inflammation and immune cell recruitment to adipose tissue, muscle and intima of atherosclerotic blood vessels. Obesity and hyperlipidemia are also associated with tissue insulin resistance and can compromise insulin delivery to muscle. The muscle/fat microvascular endothelium mediates insulin delivery and facilitates monocyte transmigration, yet its contribution to the consequences of hyperlipidemia is poorly understood. Using primary endothelial cells from human adipose tissue microvasculature (HAMEC), we investigated the effects of physiological levels of fatty acids on endothelial inflammation and function. Expression of cytokines and adhesion molecules was measured by RT-qPCR. Signaling pathways were evaluated by pharmacological manipulation and immunoblotting. Surface expression of adhesion molecules was determined by immunohistochemistry. THP1 monocyte interaction with HAMEC was measured by cell adhesion and migration across transwells. Insulin transcytosis was measured by total internal reflection fluorescence microscopy. Palmitate, but not palmitoleate, elevated the expression of IL-6, IL-8, TLR2 (Toll-like receptor 2), and intercellular adhesion molecule 1 (ICAM-1). HAMEC had markedly low fatty acid uptake and oxidation, and CD36 inhibition did not reverse the palmitate-induced expression of adhesion molecules, suggesting that inflammation did not arise from palmitate uptake/metabolism. Instead, inhibition of TLR4 to NF-κB signaling blunted palmitate-induced ICAM-1 expression. Importantly, palmitate-induced surface expression of ICAM-1 promoted monocyte binding and transmigration. Conversely, palmitate reduced insulin transcytosis, an effect reversed by TLR4 inhibition. In summary, palmitate activates inflammatory pathways in primary microvascular endothelial cells, impairing insulin transport and increasing monocyte transmigration. This behavior may contribute in vivo to reduced tissue insulin action and enhanced tissue

Time-Dependent Behavior of Microvascular Blood Flow and Oxygenation: A Predictor of Functional Outcomes.

Science.gov (United States)

Kuliga, Katarzyna Z; Gush, Rodney; Clough, Geraldine F; Chipperfield, Andrew John

2018-05-01

This study investigates the time-dependent behaviour and algorithmic complexity of low-frequency periodic oscillations in blood flux (BF) and oxygenation signals from the microvasculature. Microvascular BF and oxygenation (OXY: oxyHb, deoxyHb, totalHb, and SO 2 %) was recorded from 15 healthy young adult males using combined laser Doppler fluximetry and white light spectroscopy with local skin temperature clamped to 33  °C and during local thermal hyperaemia (LTH) at 43 °C. Power spectral density of the BF and OXY signals was evaluated within the frequency range (0.0095-1.6 Hz). Signal complexity was determined using the Lempel-Ziv (LZ) algorithm. Fold increase in BF during LTH was 15.6 (10.3, 22.8) and in OxyHb 4.8 (3.5, 5.9) (median, range). All BF and OXY signals exhibited multiple oscillatory components with clear differences in signal power distribution across frequency bands at 33 and 43 °C. Significant reduction in the intrinsic variability and complexity of the microvascular signals during LTH was found, with mean LZ complexity of BF and OxyHb falling by 25% and 49%, respectively ( ). These results provide corroboration that in human skin microvascular blood flow and oxygenation are influenced by multiple time-varying oscillators that adapt to local influences and become more predictable during increased haemodynamic flow. Recent evidence strongly suggests that the inability of microvascular networks to adapt to an imposed stressor is symptomatic of disease risk which might be assessed via BF and OXY via the combination signal analysis techniques described here.

Thrombin stimulates albumin transcytosis in lung microvascular endothelial cells via activation of acid sphingomyelinase.

Science.gov (United States)

Kuebler, Wolfgang M; Wittenberg, Claudia; Lee, Warren L; Reppien, Eike; Goldenberg, Neil M; Lindner, Karsten; Gao, Yizhuo; Winoto-Morbach, Supandi; Drab, Marek; Mühlfeld, Christian; Dombrowsky, Heike; Ochs, Matthias; Schütze, Stefan; Uhlig, Stefan

2016-04-15

Transcellular albumin transport occurs via caveolae that are abundant in lung microvascular endothelial cells. Stimulation of albumin transcytosis by proinflammatory mediators may contribute to alveolar protein leak in lung injury, yet the regulation of albumin transport and its underlying molecular mechanisms are so far incompletely understood. Here we tested the hypothesis that thrombin may stimulate transcellular albumin transport across lung microvascular endothelial cells in an acid-sphingomyelinase dependent manner. Thrombin increased the transport of fluorescently labeled albumin across confluent human lung microvascular endothelial cell (HMVEC-L) monolayers to an extent that markedly exceeds the rate of passive diffusion. Thrombin activated acid sphingomyelinase (ASM) and increased ceramide production in HMVEC-L, but not in bovine pulmonary artery cells, which showed little albumin transport in response to thrombin. Thrombin increased total caveolin-1 (cav-1) content in both whole cell lysates and lipid rafts from HMVEC-L, and this effect was blocked by inhibition of ASM or de novo protein biosynthesis. Thrombin-induced uptake of albumin into lung microvascular endothelial cells was confirmed in isolated-perfused lungs by real-time fluorescence imaging and electron microscopy of gold-labeled albumin. Inhibition of ASM attenuated thrombin-induced albumin transport both in confluent HMVEC-L and in intact lungs, whereas HMVEC-L treatment with exogenous ASM increased albumin transport and enriched lipid rafts in cav-1. Our findings indicate that thrombin stimulates transcellular albumin transport in an acid sphingomyelinase-dependent manner by inducing de novo synthesis of cav-1 and its recruitment to membrane lipid rafts. Copyright © 2016 the American Physiological Society.

Measurement of P-31 MR relaxation times and concentrations in human brain and brain tumors

International Nuclear Information System (INIS)

Roth, K.; Naruse, S.; Hubesch, B.; Gober, I.; Lawry, T.; Boska, M.; Matson, G.B.; Weiner, M.W.

1987-01-01

Measurements of high-energy phosphates and pH were made in human brain and brain tumors using P-31 MR imaging. Using a Philips Gyroscan 1.5-T MRMRS, MR images were used to select a cuboidal volume of interest and P-31 MR spectra were obtained from that volume using the ISIS technique. An external quantitation standard was used. T 1 s were measured by inversion recovery. Quantitative values for metabolites were calculated using B 1 field plot of the head coil. The results for normal brain phosphates are as follows; adenosine triphosphate, 2.2 mM; phosphocreatin, 5.3 mM; inorganic phosphate, 1.6 mM. Preliminary studies with human brain tumors show a decrease of all phosphate compounds. These experiments are the first to quantitate metabolites in human brain

"Messing with the Mind: Evolutionary Challenges to Human Brain Augmentation

Directory of Open Access Journals (Sweden)

ARTHUR eSANIOTIS

2014-09-01

Full Text Available The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understand some of the basic concepts of cognition. Therefore, this article proposes that brain-machine interfacing and nootropics are not going to produce augmented brains because we do not understand enough about how evolutionary pressures have informed the neural networks which support human cognitive faculties.

Loss of Brain Aerobic Glycolysis in Normal Human Aging.

Science.gov (United States)

Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

2017-08-01

The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling Group B Streptococcus and Blood-Brain Barrier Interaction by Using Induced Pluripotent Stem Cell-Derived Brain Endothelial Cells

OpenAIRE

Kim, Brandon J.; Bee, Olivia B.; McDonagh, Maura A.; Stebbins, Matthew J.; Palecek, Sean P.; Doran, Kelly S.; Shusta, Eric V.

2017-01-01

ABSTRACT Bacterial meningitis is a serious infection of the central nervous system (CNS) that occurs after bacteria interact with and penetrate the blood-brain barrier (BBB). The BBB is comprised of highly specialized brain microvascular endothelial cells (BMECs) that function to separate the circulation from the CNS and act as a formidable barrier for toxins and pathogens. Certain bacteria, such as Streptococcus agalactiae (group B Streptococcus [GBS]), possess the ability to interact with a...

Human-like brain hemispheric dominance in birdsong learning.

Science.gov (United States)

Moorman, Sanne; Gobes, Sharon M H; Kuijpers, Maaike; Kerkhofs, Amber; Zandbergen, Matthijs A; Bolhuis, Johan J

2012-07-31

Unlike nonhuman primates, songbirds learn to vocalize very much like human infants acquire spoken language. In humans, Broca's area in the frontal lobe and Wernicke's area in the temporal lobe are crucially involved in speech production and perception, respectively. Songbirds have analogous brain regions that show a similar neural dissociation between vocal production and auditory perception and memory. In both humans and songbirds, there is evidence for lateralization of neural responsiveness in these brain regions. Human infants already show left-sided dominance in their brain activation when exposed to speech. Moreover, a memory-specific left-sided dominance in Wernicke's area for speech perception has been demonstrated in 2.5-mo-old babies. It is possible that auditory-vocal learning is associated with hemispheric dominance and that this association arose in songbirds and humans through convergent evolution. Therefore, we investigated whether there is similar song memory-related lateralization in the songbird brain. We exposed male zebra finches to tutor or unfamiliar song. We found left-sided dominance of neuronal activation in a Broca-like brain region (HVC, a letter-based name) of juvenile and adult zebra finch males, independent of the song stimulus presented. In addition, juvenile males showed left-sided dominance for tutor song but not for unfamiliar song in a Wernicke-like brain region (the caudomedial nidopallium). Thus, left-sided dominance in the caudomedial nidopallium was specific for the song-learning phase and was memory-related. These findings demonstrate a remarkable neural parallel between birdsong and human spoken language, and they have important consequences for our understanding of the evolution of auditory-vocal learning and its neural mechanisms.

Active cooling of microvascular composites for battery packaging

Science.gov (United States)

Pety, Stephen J.; Chia, Patrick X. L.; Carrington, Stephen M.; White, Scott R.

2017-10-01

Batteries in electric vehicles (EVs) require a packaging system that provides both thermal regulation and crash protection. A novel packaging scheme is presented that uses active cooling of microvascular carbon fiber reinforced composites to accomplish this multifunctional objective. Microvascular carbon fiber/epoxy composite panels were fabricated and their cooling performance assessed over a range of thermal loads and experimental conditions. Tests were performed for different values of coolant flow rate, channel spacing, panel thermal conductivity, and applied heat flux. More efficient cooling occurs when the coolant flow rate is increased, channel spacing is reduced, and thermal conductivity of the host composite is increased. Computational fluid dynamics (CFD) simulations were also performed and correlate well with the experimental data. CFD simulations of a typical EV battery pack confirm that microvascular composite panels can adequately cool battery cells generating 500 W m-2 heat flux below 40 °C.

Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

Science.gov (United States)

Burke, Caitlin W; Price, Richard J

2010-12-15

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

Connectome imaging for mapping human brain pathways.

Science.gov (United States)

Shi, Y; Toga, A W

2017-09-01

With the fast advance of connectome imaging techniques, we have the opportunity of mapping the human brain pathways in vivo at unprecedented resolution. In this article we review the current developments of diffusion magnetic resonance imaging (MRI) for the reconstruction of anatomical pathways in connectome studies. We first introduce the background of diffusion MRI with an emphasis on the technical advances and challenges in state-of-the-art multi-shell acquisition schemes used in the Human Connectome Project. Characterization of the microstructural environment in the human brain is discussed from the tensor model to the general fiber orientation distribution (FOD) models that can resolve crossing fibers in each voxel of the image. Using FOD-based tractography, we describe novel methods for fiber bundle reconstruction and graph-based connectivity analysis. Building upon these novel developments, there have already been successful applications of connectome imaging techniques in reconstructing challenging brain pathways. Examples including retinofugal and brainstem pathways will be reviewed. Finally, we discuss future directions in connectome imaging and its interaction with other aspects of brain imaging research.

Microvascular dysfunction in the immediate aftermath of chronic total coronary occlusion recanalization.

Science.gov (United States)

Ladwiniec, Andrew; Cunnington, Michael S; Rossington, Jennifer; Thackray, Simon; Alamgir, Farquad; Hoye, Angela

2016-05-01

The aim of this study was to compare microvascular resistance under both baseline and hyperemic conditions immediately after percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) with an unobstructed reference vessel in the same patient Microvascular dysfunction has been reported to be prevalent immediately after CTO PCI. However, previous studies have not made comparison with a reference vessel. Patients with a CTO may have global microvascular and/or endothelial dysfunction, making comparison with established normal values misleading. After successful CTO PCI in 21 consecutive patients, coronary pressure and flow velocity were measured at baseline and hyperemia in distal segments of the CTO/target vessel and an unobstructed reference vessel. Hemodynamics including hyperemic microvascular resistance (HMR), basal microvascular resistance (BMR), and instantaneous minimal microvascular resistance at baseline and hyperemia were calculated and compared between reference and target/CTO vessels. After CTO PCI, BMR was reduced in the target/CTO vessel compared with the reference vessel: 3.58 mm Hg/cm/s vs 4.94 mm Hg/cm/s, difference -1.36 mm Hg/cm/s (-2.33 to -0.39, p = 0.008). We did not detect a difference in HMR: 1.82 mm Hg/cm/s vs 2.01 mm Hg/cm/s, difference -0.20 (-0.78 to 0.39, p = 0.49). Instantaneous minimal microvascular resistance correlated strongly with the length of stented segment at baseline (r = 0.63, p = 0.005) and hyperemia (r = 0.68, p = 0.002). BMR is reduced in a recanalized CTO in the immediate aftermath of PCI compared to an unobstructed reference vessel; however, HMR appears to be preserved. A longer stented segment is associated with increased microvascular resistance. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Imaging visual function of the human brain

International Nuclear Information System (INIS)

Marg, E.

1988-01-01

Imaging of human brain structure and activity with particular reference to visual function is reviewed along with methods of obtaining the data including computed tomographic (CT) scan, magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET). The literature is reviewed and the potential for a new understanding of brain visual function is discussed. PET is reviewed from basic physical principles to the most recent visual brain findings with oxygen-15. It is shown that there is a potential for submillimeter localization of visual functions with sequentially different visual stimuli designed for the temporal separation of the responses. Single photon emission computed tomography (SPECT), a less expensive substitute for PET, is also discussed. MRS is covered from basic physical principles to the current state of the art of in vivo biochemical analysis. Future possible clinical applications are discussed. Improved understanding of the functional neural organization of vision and brain will open a window to maps and circuits of human brain function.119 references

Microvascular imaging: techniques and opportunities for clinical physiological measurements

International Nuclear Information System (INIS)

Allen, John; Howell, Kevin

2014-01-01

The microvasculature presents a particular challenge in physiological measurement because the vessel structure is spatially inhomogeneous and perfusion can exhibit high variability over time. This review describes, with a clinical focus, the wide variety of methods now available for imaging of the microvasculature and their key applications. Laser Doppler perfusion imaging and laser speckle contrast imaging are established, commercially-available techniques for determining microvascular perfusion, with proven clinical utility for applications such as burn-depth assessment. Nailfold capillaroscopy is also commercially available, with significant published literature that supports its use for detecting microangiopathy secondary to specific connective tissue diseases in patients with Raynaud's phenomenon. Infrared thermography measures skin temperature and not perfusion directly, and it has only gained acceptance for some surgical and peripheral microvascular applications. Other emerging technologies including imaging photoplethysmography, optical coherence tomography, photoacoustic tomography, hyperspectral imaging, and tissue viability imaging are also described to show their potential as techniques that could become established tools for clinical microvascular assessment. Growing interest in the microcirculation has helped drive the rapid development in perfusion imaging of the microvessels, bringing exciting opportunities in microvascular research. (topical review)

Pilot study on microvascular anastomosis: performance and future educational prospects.

Science.gov (United States)

Berretti, G; Colletti, G; Parrinello, G; Iavarone, A; Vannucchi, P; Deganello, A

2017-11-30

The introduction of microvascular free flaps has revolutionised modern reconstructive surgery. Unfortunately, access to training opportunities at standardised training courses is limited and expensive. We designed a pilot study on microvascular anastomoses with the aim of verifying if a short course, easily reproducible, could transmit microvascular skills to participants; if the chosen pre-test was predictive of final performance; and if age could influence the outcome. A total of 30 participants (10 students, 10 residents and 10 surgeons) without any previous microvascular experience were instructed and tested during a single 3 to 5 hour course. The two microanastomoses evaluated were the first ever performed by each participant. More than the half of the cohort was able to produce both patent microanastomoses in less than 2 hours; two-thirds of the attempted microanastomoses were patent. The pretest predicted decent scores from poor performances with a sensitivity of 61.5%, specificity of 100%, positive predictive value of 100% and negative predictive value of 40%. Students and residents obtained significantly higher scores than surgeons. Since our course model is short, cost-effective and highly reproducible, it could be introduced and implemented anywhere as an educational prospect for preselecting young residents showing talent and natural predisposition and having ambitions towards microvascular reconstructive surgery. © Copyright by Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale.

Ionising radiation and the developing human brain

International Nuclear Information System (INIS)

Schull, W.J.

1991-01-01

This article reviews the effects of radiation exposure of the developing human brain. Much of the evidence has come from the prenatally exposed in Hiroshima and Nagasaki. The effects on development age, mental retardation, head size, neuromuscular performance, intelligence tests, school performance and the occurrence of convulsions are discussed. Other topics covered include the biological nature of the damage to the brain, risk estimates in human and problems in radiation protection. (UK)

Sleep restriction impairs blood-brain barrier function.

Science.gov (United States)

He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong

2014-10-29

The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice. Copyright © 2014 the authors 0270-6474/14/3414697-10$15.00/0.

Flavonoids targeting of IκB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells

Directory of Open Access Journals (Sweden)

Tahanian E

2011-05-01

Full Text Available Elizabeth Tahanian¹, Luis Arguello Sanchez¹, Tze Chieh Shiao², René Roy², Borhane Annabi¹¹Centre de Recherche BioMED, ²Centre de Recherche PharmaQAM, Département de chimie, Université du Québec à Montréal, QC, CanadaAbstract: Brain endothelial cells play an essential role as structural and functional components of the blood–brain barrier (BBB. Increased BBB breakdown and brain injury are associated with neuroinflammation and are thought to trigger mechanisms involving matrix metalloproteinase upregulation. Emerging evidence also indicates that cyclooxygenase (COX inhibition limits BBB disruption, but the mechanisms linking metalloproteinase to COX remain unknown. In this study, we sought to investigate the nuclear factor-kappa B (NF-κB signaling pathway, a common pathway in both the regulation of matrix metalloproteinase-9 (MMP-9 and COX-2 expression, and the inhibitory properties of several chemopreventive flavonoids. Human brain microvascular endothelial cells were treated with a combination of phorbol 12-myristate 13-acetate (PMA, a carcinogen documented to increase MMP-9 and COX-2 through NF-κB, and several naturally occurring flavonoids. Among the molecules tested, we found that fisetin, apigenin, and luteolin specifically and dose-dependently antagonized PMA-induced COX-2 and MMP-9 gene and protein expressions as assessed by qRT-PCR, immunoblotting, and zymography respectively. We further demonstrate that flavonoids impact on IκK-mediated phosphorylation activity as demonstrated by the inhibition of PMA-induced IκB phosphorylation levels. Our results suggest that BBB disruption during neuroinflammation could be pharmacologically reduced by a specific class of flavonoids acting as NF-κB signal transduction inhibitors.Keywords: blood–brain barrier, flavonoids, neuroinflammation, NF-κB signal transduction inhibitors

A Culture-Behavior-Brain Loop Model of Human Development.

Science.gov (United States)

Han, Shihui; Ma, Yina

2015-11-01

Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

Science.gov (United States)

Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu; Preuss, Todd M; Bruner, Emiliano

2017-01-01

The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage. © 2017 S. Karger AG, Basel.

Effects of Sex Steroids in the Human Brain.

Science.gov (United States)

Nguyen, Tuong-Vi; Ducharme, Simon; Karama, Sherif

2017-11-01

Sex steroids are thought to play a critical developmental role in shaping both cortical and subcortical structures in the human brain. Periods of profound changes in sex steroids invariably coincide with the onset of sex differences in mental health vulnerability, highlighting the importance of sex steroids in determining sexual differentiation of the brain. Yet, most of the evidence for the central effects of sex steroids relies on non-human studies, as several challenges have limited our understanding of these effects in humans: the lack of systematic assessment of the human sex steroid metabolome, the different developmental trajectories of specific sex steroids, the impact of genetic variation and epigenetic changes, and the plethora of interactions between sex steroids, sex chromosomes, neurotransmitters, and other hormonal systems. Here we review how multimodal strategies may be employed to bridge the gap between the basic and clinical understanding of sex steroid-related changes in the human brain.

Insulin-resistant glucose metabolism in patients with microvascular angina--syndrome X

DEFF Research Database (Denmark)

Vestergaard, H; Skøtt, P; Steffensen, R

1995-01-01

Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study was to exa......Studies in patients with microvascular angina (MA) or the cardiologic syndrome X have shown a hyperinsulinemic response to an oral glucose challenge, suggesting insulin resistance and a role for increased serum insulin in coronary microvascular dysfunction. The aim of the present study...... was to examine whether patients with MA are insulin-resistant. Nine patients with MA and seven control subjects were studied. All were sedentary and glucose-tolerant. Coronary arteriography was normal in all participants, and exercise-induced coronary ischemia was demonstrated in all MA patients. A euglycemic...... metabolism (8.4 +/- 0.9 v 12.5 +/- 1.3 mg.kg FFM-1.min-1, P

Radionuclide assessment of pulmonary microvascular permeability

Energy Technology Data Exchange (ETDEWEB)

Groeneveld, A.B.J. [Medical Intensive Care Unit, Department of Internal Medicine, Free University Hospital, De Boelelaan 1117, 1081 HV Amsterdam (Netherlands)

1997-04-01

The literature has been reviewed to evaluate the technique and clinical value of radionuclide measurements of microvascular permeability and oedema formation in the lungs. Methodology, modelling and interpretation vary widely among studies. Nevertheless, most studies agree on the fact that the measurement of permeability via pulmonary radioactivity measurements of intravenously injected radiolabelled proteins versus that in the blood pool, the so-called pulmonary protein transport rate (PTR), can assist the clinician in discriminating between permeability oedema of the lungs associated with the adult respiratory distress syndrome (ARDS) and oedema caused by an increased filtration pressure, for instance in the course of cardiac disease, i.e. pressure-induced pulmonary oedema. Some of the techniques used to measure PTR are also able to detect subclinical forms of lung microvascular injury not yet complicated by permeability oedema. This may occur after cardiopulmonary bypass and major vascular surgery, for instance. By paralleling the clinical severity and course of the ARDS, the PTR method may also serve as a tool to evaluate new therapies for the syndrome. Taken together, the currently available radionuclide methods, which are applicable at the bedside in the intensive care unit, may provide a gold standard for detecting minor and major forms of acute microvascular lung injury, and for evaluating the severity, course and response to treatment. (orig.). With 2 tabs.

Profile of Microvascular Disease in Type 2 Diabetes in a Tertiary ...

African Journals Online (AJOL)

Background: Diabetes mellitus (DM) is a metabolic disorder complicated by microvascular and macrovascular diseases. The clinical profile of these complications has not been adequately studied in many tertiary health care centers in India. Aim: The authors studied the clinical profile of microvascular diabetes ...

Plasmalemmal V-H+-ATPases regulate intracellular pH in human lung microvascular endothelial cells

International Nuclear Information System (INIS)

Rojas, Jose D.; Sennoune, Souad R.; Maiti, Debasish; Martinez, Gloria M.; Bakunts, Karina; Wesson, Donald E.; Martinez-Zaguilan, Raul

2004-01-01

The lung endothelium layer is exposed to continuous CO 2 transit which exposes the endothelium to a substantial acid load that could be detrimental to cell function. The Na + /H + exchanger and HCO 3 - -dependent H + -transporting mechanisms regulate intracellular pH (pH cyt ) in most cells. Cells that cope with high acid loads might require additional primary energy-dependent mechanisms. V-H + -ATPases localized at the plasma membranes (pmV-ATPases) have emerged as a novel pH regulatory system. We hypothesized that human lung microvascular endothelial (HLMVE) cells use pmV-ATPases, in addition to Na + /H + exchanger and HCO 3 - -based H + -transporting mechanisms, to maintain pH cyt homeostasis. Immunocytochemical studies revealed V-H + -ATPase at the plasma membrane, in addition to the predicted distribution in vacuolar compartments. Acid-loaded HLMVE cells exhibited proton fluxes in the absence of Na + and HCO 3 - that were similar to those observed in the presence of either Na + , or Na + and HCO 3 - . The Na + - and HCO 3 - -independent pH cyt recovery was inhibited by bafilomycin A 1 , a V-H + -ATPase inhibitor. These studies show a Na + - and HCO 3 - -independent pH cyt regulatory mechanism in HLMVE cells that is mediated by pmV-ATPases

Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay)

International Nuclear Information System (INIS)

Dorn, A.; Bernstein, H.G.; Rinne, A.; Hahn, H.J.; Ziegler, M.

1983-01-01

The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the 'brain insulin' is - at least in part - produced in the CNS. (author)

Endothelium-targeted overexpression of heat shock protein 27 ameliorates blood–brain barrier disruption after ischemic brain injury

Science.gov (United States)

Jiang, Xiaoyan; Zhang, Lili; Pu, Hongjian; Hu, Xiaoming; Zhang, Wenting; Cai, Wei; Gao, Yanqin; Leak, Rehana K.; Keep, Richard F.; Bennett, Michael V. L.; Chen, Jun

2017-01-01

The damage borne by the endothelial cells (ECs) forming the blood–brain barrier (BBB) during ischemic stroke and other neurological conditions disrupts the structure and function of the neurovascular unit and contributes to poor patient outcomes. We recently reported that structural aberrations in brain microvascular ECs—namely, uncontrolled actin polymerization and subsequent disassembly of junctional proteins, are a possible cause of the early onset BBB breach that arises within 30–60 min of reperfusion after transient focal ischemia. Here, we investigated the role of heat shock protein 27 (HSP27) as a direct inhibitor of actin polymerization and protectant against BBB disruption after ischemia/reperfusion (I/R). Using in vivo and in vitro models, we found that targeted overexpression of HSP27 specifically within ECs—but not within neurons—ameliorated BBB impairment 1–24 h after I/R. Mechanistically, HSP27 suppressed I/R-induced aberrant actin polymerization, stress fiber formation, and junctional protein translocation in brain microvascular ECs, independent of its protective actions against cell death. By preserving BBB integrity after I/R, EC-targeted HSP27 overexpression attenuated the infiltration of potentially destructive neutrophils and macrophages into brain parenchyma, thereby improving long-term stroke outcome. Notably, early poststroke administration of HSP27 attached to a cell-penetrating transduction domain (TAT-HSP27) rapidly elevated HSP27 levels in brain microvessels and ameliorated I/R-induced BBB disruption and subsequent neurological deficits. Thus, the present study demonstrates that HSP27 can function at the EC level to preserve BBB integrity after I/R brain injury. HSP27 may be a therapeutic agent for ischemic stroke and other neurological conditions involving BBB breakdown. PMID:28137866

Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling

Directory of Open Access Journals (Sweden)

Shi Xianglin

2009-01-01

Full Text Available Abstract Background Engineered iron nanoparticles are being explored for the development of biomedical applications and many other industry purposes. However, to date little is known concerning the precise mechanisms of translocation of iron nanoparticles into targeted tissues and organs from blood circulation, as well as the underlying implications of potential harmful health effects in human. Results The confocal microscopy imaging analysis demonstrates that exposure to engineered iron nanoparticles induces an increase in cell permeability in human microvascular endothelial cells. Our studies further reveal iron nanoparticles enhance the permeability through the production of reactive oxygen species (ROS and the stabilization of microtubules. We also showed Akt/GSK-3β signaling pathways are involved in iron nanoparticle-induced cell permeability. The inhibition of ROS demonstrate ROS play a major role in regulating Akt/GSK-3β – mediated cell permeability upon iron nanoparticle exposure. These results provide new insights into the bioreactivity of engineered iron nanoparticles which can inform potential applications in medical imaging or drug delivery. Conclusion Our results indicate that exposure to iron nanoparticles induces an increase in endothelial cell permeability through ROS oxidative stress-modulated microtubule remodeling. The findings from this study provide new understandings on the effects of nanoparticles on vascular transport of macromolecules and drugs.

Irradiation combined with SU5416: Microvascular changes and growth delay in a human xenograft glioblastoma tumor line

International Nuclear Information System (INIS)

Schuuring, Janneke; Bussink, Johan; Bernsen, Hans; Peeters, Wenny; Kogel, Albert J. van der

2005-01-01

Purpose: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. Methods and materials: A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. Results: SU5416, when combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. Conclusions: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone

Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules

OpenAIRE

Zhang, Wujie; Choi, Jung K.; He, Xiaoming

2017-01-01

Construction of vascularized tissues is one of the major challenges of tissue engineering. The goal of this study was to engineer 3D microvascular tissues by incorporating the HUVEC-CS cells with a collagen/alginate-chitosan (AC) microcapsule scaffold. In the presence of AC microcapsules, a 3D vascular-like network was clearly observable. The results indicated the importance of AC microcapsules in engineering microvascular tissues -- providing support and guiding alignment of HUVEC-CS cells. ...

The intrinsic geometry of the human brain connectome.

Science.gov (United States)

Ye, Allen Q; Ajilore, Olusola A; Conte, Giorgio; GadElkarim, Johnson; Thomas-Ramos, Galen; Zhan, Liang; Yang, Shaolin; Kumar, Anand; Magin, Richard L; G Forbes, Angus; Leow, Alex D

2015-12-01

This paper describes novel methods for constructing the intrinsic geometry of the human brain connectome using dimensionality-reduction techniques. We posit that the high-dimensional, complex geometry that represents this intrinsic topology can be mathematically embedded into lower dimensions using coupling patterns encoded in the corresponding brain connectivity graphs. We tested both linear and nonlinear dimensionality-reduction techniques using the diffusion-weighted structural connectome data acquired from a sample of healthy subjects. Results supported the nonlinearity of brain connectivity data, as linear reduction techniques such as the multidimensional scaling yielded inferior lower-dimensional embeddings. To further validate our results, we demonstrated that for tractography-derived structural connectome more influential regions such as rich-club members of the brain are more centrally mapped or embedded. Further, abnormal brain connectivity can be visually understood by inspecting the altered geometry of these three-dimensional (3D) embeddings that represent the topology of the human brain, as illustrated using simulated lesion studies of both targeted and random removal. Last, in order to visualize brain's intrinsic topology we have developed software that is compatible with virtual reality technologies, thus allowing researchers to collaboratively and interactively explore and manipulate brain connectome data.

Neurospin Seminar: From the Proton to the Human Brain

CERN Multimedia

CERN. Geneva

2016-01-01

From the Proton to the Human Brain Speaker: Prof Denis Le Bihan Abstract: The understanding of the human brain is one of the main scientific challenges of the 21st century. In the early 2000s the French Atomic Energy Commission (CEA) launched a program to conceive and build a “human brain explorer”, the first human MRI scanner operating at 11.7T. This scanner was envisioned to be part of the ambitious Iseult project, bridging together industrial and academic partners to push the limits of molecular neuroimaging, from mouse to man, using Ultra-High Field (UHF) MRI. In this seminar a summary of the main features of this magnet, and the neuroscience and medical targets of NeuroSpin where this outstanding instrument will be installed in 2017 will be surveyed. The unprecedented resolution and the new contrasts allowed by such UHF magnets, in combination with innovative concepts in physics and neurobiology, will allow to explore the human brain at a mesoscale at which everything remains to d...

Integration of Self-Assembled Microvascular Networks with Microfabricated PEG-Based Hydrogels.

Science.gov (United States)

Cuchiara, Michael P; Gould, Daniel J; McHale, Melissa K; Dickinson, Mary E; West, Jennifer L

2012-11-07

Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co-culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self-assembly and employs an anastomotic interface for integration of self-assembled micro-vascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra-vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo.

Neutrophilia, gelatinase release and microvascular leakage induced by human mast cell tryptase in a mouse model: Lack of a role of protease-activated receptor 2 (PAR2).

Science.gov (United States)

Khedr, M E M S; Abdelmotelb, A M; Pender, S L F; Zhou, X; Walls, A F

2018-05-01

Tryptase, the most abundant protease of the human mast cell, has been implicated as a key mediator of allergic inflammation that acts through activation of PAR2. To investigate the contribution of PAR2 in the pro-inflammatory actions mediated by tryptase in a mice model. We have injected recombinant human βII-tryptase into the peritoneum of PAR2-deficient and wild-type C57BL/6 mice. After 6, 12 and 24 hours, mice were killed, peritoneal lavage performed and inflammatory changes investigated. Tryptase stimulated an increase in neutrophil numbers in the peritoneum, but responses did not differ between PAR2-deficient and wild-type mice. Heat inactivation of tryptase or pre-incubation with a selective tryptase inhibitor reduced neutrophilia, but neutrophil accumulation was not elicited with a peptide agonist of PAR2 (SLIGRL-NH 2 ). Zymography indicated that tryptase stimulated the release of matrix metalloproteinases (MMP) 2 and 9 in the peritoneum of both mouse strains. Studies involving immunomagnetic isolation of neutrophils suggested that neutrophils represent the major cellular source of tryptase-induced MMP2 and MMP9. At 24 hours after tryptase injection, there was increased microvascular leakage as indicated by high levels of albumin in peritoneal lavage fluid, and this appeared to be partially abolished by heat-inactivating tryptase or addition of a protease inhibitor. There was no corresponding increase in levels of histamine or total protein. The extent of tryptase-induced microvascular leakage or gelatinase release into the peritoneum did not differ between PAR2-deficient and wild-type mice. Our findings indicate that tryptase is a potent stimulus for neutrophil accumulation, MMP release and microvascular leakage. Although these actions required an intact catalytic site, the primary mechanism of tryptase in vivo would appear to involve processes independent of PAR2. © 2018 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Therapeutic Effects of PPARα on Neuronal Death and Microvascular Impairment

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Elizabeth P. Moran

2015-01-01

Full Text Available Peroxisome-proliferator activated receptor-alpha (PPARα is a broadly expressed nuclear hormone receptor and is a transcription factor for diverse target genes possessing a PPAR response element (PPRE in the promoter region. The PPRE is highly conserved, and PPARs thus regulate transcription of an extensive array of target genes involved in energy metabolism, vascular function, oxidative stress, inflammation, and many other biological processes. PPARα has potent protective effects against neuronal cell death and microvascular impairment, which have been attributed in part to its antioxidant and anti-inflammatory properties. Here we discuss PPARα’s effects in neurodegenerative and microvascular diseases and also recent clinical findings that identified therapeutic effects of a PPARα agonist in diabetic microvascular complications.

Insights into Brain Glycogen Metabolism: THE STRUCTURE OF HUMAN BRAIN GLYCOGEN PHOSPHORYLASE.

Science.gov (United States)

Mathieu, Cécile; Li de la Sierra-Gallay, Ines; Duval, Romain; Xu, Ximing; Cocaign, Angélique; Léger, Thibaut; Woffendin, Gary; Camadro, Jean-Michel; Etchebest, Catherine; Haouz, Ahmed; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2016-08-26

Brain glycogen metabolism plays a critical role in major brain functions such as learning or memory consolidation. However, alteration of glycogen metabolism and glycogen accumulation in the brain contributes to neurodegeneration as observed in Lafora disease. Glycogen phosphorylase (GP), a key enzyme in glycogen metabolism, catalyzes the rate-limiting step of glycogen mobilization. Moreover, the allosteric regulation of the three GP isozymes (muscle, liver, and brain) by metabolites and phosphorylation, in response to hormonal signaling, fine-tunes glycogenolysis to fulfill energetic and metabolic requirements. Whereas the structures of muscle and liver GPs have been known for decades, the structure of brain GP (bGP) has remained elusive despite its critical role in brain glycogen metabolism. Here, we report the crystal structure of human bGP in complex with PEG 400 (2.5 Å) and in complex with its allosteric activator AMP (3.4 Å). These structures demonstrate that bGP has a closer structural relationship with muscle GP, which is also activated by AMP, contrary to liver GP, which is not. Importantly, despite the structural similarities between human bGP and the two other mammalian isozymes, the bGP structures reveal molecular features unique to the brain isozyme that provide a deeper understanding of the differences in the activation properties of these allosteric enzymes by the allosteric effector AMP. Overall, our study further supports that the distinct structural and regulatory properties of GP isozymes contribute to the different functions of muscle, liver, and brain glycogen. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Infrasounds and biorhythms of the human brain

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Panuszka, Ryszard; Damijan, Zbigniew; Kasprzak, Cezary; McGlothlin, James

2002-05-01

Low Frequency Noise (LFN) and infrasound has begun a new public health hazard. Evaluations of annoyance of (LFN) on human occupational health were based on standards where reactions of human auditory system and vibrations of parts of human body were small. Significant sensitivity has been observed on the central nervous system from infrasonic waves especially below 10 Hz. Observed follow-up effects in the brain gives incentive to study the relationship between parameters of waves and reactions obtained of biorhythms (EEG) and heart action (EKG). New results show the impact of LFN on the electrical potentials of the brain are dependent on the pressure waves on the human body. Electrical activity of circulatory system was also affected. Signals recorded in industrial workplaces were duplicated by loudspeakers and used to record data from a typical LFN spectra with 5 and 7 Hz in a laboratory chamber. External noise, electromagnetic fields, temperature, dust, and other elements were controlled. Results show not only a follow-up effect in the brain but also a result similar to arrhythmia in the heart. Relaxations effects were observed of people impacted by waves generated from natural sources such as streams and waterfalls.

Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

Science.gov (United States)

Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

2016-03-01

Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

Is the social brain theory applicable to human individual differences? Relationship between sociability personality dimension and brain size.

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Horváth, Klára; Martos, János; Mihalik, Béla; Bódizs, Róbert

2011-06-17

Our study intends to examine whether the social brain theory is applicable to human individual differences. According to the social brain theory primates have larger brains as it could be expected from their body sizes due to the adaptation to a more complex social life. Regarding humans there were few studies about the relationship between theory of mind and frontal and temporal brain lobes. We hypothesized that these brain lobes, as well as the whole cerebrum and neocortex are in connection with the Sociability personality dimension that is associated with individuals' social lives. Our findings support this hypothesis as Sociability correlated positively with the examined brain structures if we control the effects of body size differences and age. These results suggest that the social brain theory can be extended to human interindividual differences and they have some implications to personality psychology too.

Sigma and opioid receptors in human brain tumors

International Nuclear Information System (INIS)

Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J.

1990-01-01

Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using [ 3 H] 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: μ, [D-ala 2 , mePhe 4 , gly-ol 5 ] enkephalin (DAMGE); κ, ethylketocyclazocine (EKC) or U69,593; δ, [D-pen 2 , D-pen 5 ] enkephalin (DPDPE) or [D-ala 2 , D-leu 5 ] enkephalin (DADLE) with μ suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. κ opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed

Gene expression in the aging human brain: an overview.

Science.gov (United States)

Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

2016-03-01

The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

Variable ATP yields and uncoupling of oxygen consumption in human brain

DEFF Research Database (Denmark)

Gjedde, Albert; Aanerud, Joel; Peterson, Ericka

2011-01-01

normalized the metabolic rate to the population average of that region. Coefficients of variation ranged from 10 to 15% in the different regions of the human brain and the normalized regional metabolic rates ranged from 70% to 140% of the population average for each region, equal to a two-fold variation......The distribution of brain oxidative metabolism values among healthy humans is astoundingly wide for a measure that reflects normal brain function and is known to change very little with most changes of brain function. It is possible that the part of the oxygen consumption rate that is coupled...... to ATP turnover is the same in all healthy human brains, with different degrees of uncoupling explaining the variability of total oxygen consumption among people. To test the hypothesis that about 75% of the average total oxygen consumption of human brains is common to all individuals, we determined...

Sex differences in brain organization: implications for human communication.

Science.gov (United States)

Hanske-Petitpierre, V; Chen, A C

1985-12-01

This article reviews current knowledge in two major research domains: sex differences in neuropsychophysiology, and in human communication. An attempt was made to integrate knowledge from several areas of brain research with human communication and to clarify how such a cooperative effort may be beneficial to both fields of study. By combining findings from the area of brain research, a communication paradigm was developed which contends that brain-related sex differences may reside largely in the area of communication of emotion.

Contacting co-culture of human retinal microvascular endothelial cells alters barrier function of human embryonic stem cell derived retinal pigment epithelial cells.

Science.gov (United States)

Skottman, H; Muranen, J; Lähdekorpi, H; Pajula, E; Mäkelä, K; Koivusalo, L; Koistinen, A; Uusitalo, H; Kaarniranta, K; Juuti-Uusitalo, K

2017-10-01

Here we evaluated the effects of human retinal microvascular endothelial cells (hREC) on mature human embryonic stem cell (hESC) derived retinal pigment epithelial (RPE) cells. The hESC-RPE cells (Regea08/017, Regea08/023 or Regea11/013) and hREC (ACBRI 181) were co-cultured on opposite sides of transparent membranes for up to six weeks. Thereafter barrier function, small molecule permeability, localization of RPE and endothelial cell marker proteins, cellular fine structure, and growth factor secretion of were evaluated. After co-culture, the RPE specific CRALBP and endothelial cell specific von Willebrand factor were appropriately localized. In addition, the general morphology, pigmentation, and fine structure of hESC-RPE cells were unaffected. Co-culture increased the barrier function of hESC-RPE cells, detected both with TEER measurements and cumulative permeability of FD4 - although the differences varied among the cell lines. Co-culturing significantly altered VEGF and PEDF secretion, but again the differences were cell line specific. The results of this study showed that co-culture with hREC affects hESC-RPE functionality. In addition, co-culture revealed drastic cell line specific differences, most notably in growth factor secretion. This model has the potential to be used as an in vitro outer blood-retinal barrier model for drug permeability testing. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Optically measured microvascular blood flow contrast of malignant breast tumors.

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Regine Choe

Full Text Available Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS, a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63; tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66, and using normal tissue in the contralateral breast was 2.27 (1.90-2.70. Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography.

Gap filling of 3-D microvascular networks by tensor voting.

Science.gov (United States)

Risser, L; Plouraboue, F; Descombes, X

2008-05-01

We present a new algorithm which merges discontinuities in 3-D images of tubular structures presenting undesirable gaps. The application of the proposed method is mainly associated to large 3-D images of microvascular networks. In order to recover the real network topology, we need to fill the gaps between the closest discontinuous vessels. The algorithm presented in this paper aims at achieving this goal. This algorithm is based on the skeletonization of the segmented network followed by a tensor voting method. It permits to merge the most common kinds of discontinuities found in microvascular networks. It is robust, easy to use, and relatively fast. The microvascular network images were obtained using synchrotron tomography imaging at the European Synchrotron Radiation Facility. These images exhibit samples of intracortical networks. Representative results are illustrated.

Mapping human whole-brain structural networks with diffusion MRI.

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Patric Hagmann

Full Text Available Understanding the large-scale structural network formed by neurons is a major challenge in system neuroscience. A detailed connectivity map covering the entire brain would therefore be of great value. Based on diffusion MRI, we propose an efficient methodology to generate large, comprehensive and individual white matter connectional datasets of the living or dead, human or animal brain. This non-invasive tool enables us to study the basic and potentially complex network properties of the entire brain. For two human subjects we find that their individual brain networks have an exponential node degree distribution and that their global organization is in the form of a small world.

Cognitive genomics: Linking genes to behavior in the human brain

Directory of Open Access Journals (Sweden)

Genevieve Konopka

2017-02-01

Full Text Available Correlations of genetic variation in DNA with functional brain activity have already provided a starting point for delving into human cognitive mechanisms. However, these analyses do not provide the specific genes driving the associations, which are complicated by intergenic localization as well as tissue-specific epigenetics and expression. The use of brain-derived expression datasets could build upon the foundation of these initial genetic insights and yield genes and molecular pathways for testing new hypotheses regarding the molecular bases of human brain development, cognition, and disease. Thus, coupling these human brain gene expression data with measurements of brain activity may provide genes with critical roles in brain function. However, these brain gene expression datasets have their own set of caveats, most notably a reliance on postmortem tissue. In this perspective, I summarize and examine the progress that has been made in this realm to date, and discuss the various frontiers remaining, such as the inclusion of cell-type-specific information, additional physiological measurements, and genomic data from patient cohorts.

Transcranial magnetic stimulation and the human brain

Science.gov (United States)

Hallett, Mark

2000-07-01

Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

Using human brain activity to guide machine learning.

Science.gov (United States)

Fong, Ruth C; Scheirer, Walter J; Cox, David D

2018-03-29

Machine learning is a field of computer science that builds algorithms that learn. In many cases, machine learning algorithms are used to recreate a human ability like adding a caption to a photo, driving a car, or playing a game. While the human brain has long served as a source of inspiration for machine learning, little effort has been made to directly use data collected from working brains as a guide for machine learning algorithms. Here we demonstrate a new paradigm of "neurally-weighted" machine learning, which takes fMRI measurements of human brain activity from subjects viewing images, and infuses these data into the training process of an object recognition learning algorithm to make it more consistent with the human brain. After training, these neurally-weighted classifiers are able to classify images without requiring any additional neural data. We show that our neural-weighting approach can lead to large performance gains when used with traditional machine vision features, as well as to significant improvements with already high-performing convolutional neural network features. The effectiveness of this approach points to a path forward for a new class of hybrid machine learning algorithms which take both inspiration and direct constraints from neuronal data.

Microvascular endothelial function and cognitive performance: The ELSA-Brasil cohort study.

Science.gov (United States)

Brant, Luisa; Bos, Daniel; Araujo, Larissa Fortunato; Ikram, M Arfan; Ribeiro, Antonio Lp; Barreto, Sandhi M

2018-06-01

Impaired microvascular endothelial function may be implicated in the etiology of cognitive decline. Yet, current data on this association are inconsistent. Our objective is to investigate the relation of microvascular endothelial function to cognitive performance in the ELSA-Brasil cohort study. A total of 1521 participants from ELSA-Brasil free of dementia underwent peripheral arterial tonometry (PAT) to quantify microvascular endothelial function (PAT-ratio and mean baseline pulse amplitude (BPA)) and cognitive tests that covered the domains of memory, verbal fluency, and executive function at baseline. Cognitive tests in participants aged 55 years old and above were repeated during the second examination (mean follow-up: 3.5 (0.3) years). Linear regression and generalized linear models were used to evaluate the association between endothelial function, global cognitive performance, and performance on specific cognitive domains. In unadjusted cross-sectional analyses, we found that BPA and PAT-ratio were associated with worse global cognitive performance (mean difference for BPA: -0.07, 95% CI: -0.11; -0.03, p<0.01; mean difference for PAT-ratio: 0.11, 95% CI: 0.01; 0.20, p=0.02), worse performance on learning, recall, and word recognition tests (BPA: -0.87, 95% CI: -1.21; -0.52, p<0.01; PAT-ratio: 1.58, 95% CI: 0.80; 2.36, p<0.01), and only BPA was associated with worse performance in verbal fluency tests (-0.70, 95% CI: -1.19; -0.21, p<0.01). Adjustments for age, sex, and level of education rendered the associations statistically non-significant. Longitudinally, there was no association between microvascular endothelial and cognitive functions. The associations between microvascular endothelial function and cognition are explained by age, sex, and educational level. Measures of microvascular endothelial function may be of limited value with regard to preclinical cognitive deficits.

Short parietal lobe connections of the human and monkey brain

DEFF Research Database (Denmark)

Catani, Marco; Robertsson, Naianna; Beyh, Ahmad

2017-01-01

projections were reconstructed for both species and results compared to identify similarities or differences in tract anatomy (i.e., trajectories and cortical projections). In addition, post-mortem dissections were performed in a human brain. The largest tract identified in both human and monkey brains...... and angular gyri of the inferior parietal lobule in humans but only to the supramarginal gyrus in the monkey brain. The third tract connects the postcentral gyrus to the anterior region of the superior parietal lobule and is more prominent in monkeys compared to humans. Finally, short U-shaped fibres...... and monkeys with some differences for those areas that have cytoarchitectonically distinct features in humans. The overall pattern of intraparietal connectivity supports the special role of the inferior parietal lobule in cognitive functions characteristic of humans....

Expression of iron-related genes in human brain and brain tumors

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Britton Robert S

2009-04-01

Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

Studying frequency processing of the brain to enhance long-term memory and develop a human brain protocol.

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Friedrich, Wernher; Du, Shengzhi; Balt, Karlien

2015-01-01

The temporal lobe in conjunction with the hippocampus is responsible for memory processing. The gamma wave is involved with this process. To develop a human brain protocol, a better understanding of the relationship between gamma and long-term memory is vital. A more comprehensive understanding of the human brain and specific analogue waves it uses will support the development of a human brain protocol. Fifty-eight participants aged between 6 and 60 years participated in long-term memory experiments. It is envisaged that the brain could be stimulated through binaural beats (sound frequency) at 40 Hz (gamma) to enhance long-term memory capacity. EEG recordings have been transformed to sound and then to an information standard, namely ASCII. Statistical analysis showed a proportional relationship between long-term memory and gamma activity. Results from EEG recordings indicate a pattern. The pattern was obtained through the de-codification of an EEG recording to sound and then to ASCII. Stimulation of gamma should enhance long term memory capacity. More research is required to unlock the human brains' protocol key. This key will enable the processing of information directly to and from human memory via gamma, the hippocampus and the temporal lobe.

Fluid resuscitation following a burn injury: implications of a mathematical model of microvascular exchange.

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Bert, J; Gyenge, C; Bowen, B; Reed, R; Lund, T

1997-03-01

A validated mathematical model of microvascular exchange in thermally injured humans has been used to predict the consequences of different forms of resuscitation and potential modes of action of pharmaceuticals on the distribution and transport of fluid and macromolecules in the body. Specially, for 10 and/or 50 per cent burn surface area injuries, predictions are presented for no resuscitation, resuscitation with the Parkland formula (a high fluid and low protein formulation) and resuscitation with the Evans formula (a low fluid and high protein formulation). As expected, Parkland formula resuscitation leads to interstitial accumulation of excess fluid, while use of the Evans formula leads to interstitial accumulation of excessive amounts of proteins. The hypothetical effects of pharmaceuticals on the transport barrier properties of the microvascular barrier and on the highly negative tissue pressure generated postburn in the injured tissue were also investigated. Simulations predict a relatively greater amelioration of the acute postburn edema through modulation of the postburn tissue pressure effects.

Studies of pathological dynamics after microvascular injury using nonlinear optical methods

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Rosidi, Nathanael L.

Microvascular lesions are a common feature in the aging brain and clinical evidence has correlated microvascular pathology with the development of neurodegenerative diseases such as Alzheimer's disease and dementia. Traditional animal models that replicate hemorrhagic and ischemic lesions in the brain typically affect large regions in the cortex and do not reproduce the small-scale lesions linked to neurodegeneration that likely stem from injuries to single microvessels. Due in part to this lack of small-scale injury animal models, there remains an incomplete understanding of the cellular and pathophysiological dynamics following small-scale vascular lesions, making progress on therapeutic strategies difficult. We used tightly focused femtosecond laser pulses to injure single penetrating arterioles (PA) (i.e., arterioles that plunge into the brain) in the cortex of live anesthetized rodents and used two-photon excited fluorescence (2PEF) imaging to quantify blood flow changes and to determine the time course of pathological consequences in the brain after injury. We find that after ischemic occlusion of a PA, nearby pial and penetrating arterioles do not actively compensate for the reduction of blood flow observed near the occluded blood vessel. We find that capillaries connected downstream to the clotted vessel dilate but other capillaries in the vicinity do not, suggesting that any compensatory signal that results in a physiological response travels vascularly. We ruptured individual PAs to induce microhemorrhages that resulted in extravasation of blood into the parenchyma. We find that tissue compression due to the hematoma does not collapse capillaries and cause acute ischemia. 2PEF imaging of mice expressing yellow fluorescent protein (YFP) in a subset of cortical neurons revealed no dendrite degeneration out to seven days after microhemorrhage. However, we did observe an inflammatory response by microglia/macrophages as quickly as 1.5-hrs after

Validation of In Vitro Cell-Based Human Blood-Brain Barrier Model Using Clinical Positron Emission Tomography Radioligands To Predict In Vivo Human Brain Penetration

International Nuclear Information System (INIS)

Mabondzo, A.; Guyot, A.C.; Bottlaender, M.; Deverre, J.R.; Tsaouin, K.; Balimane, P.V.

2010-01-01

We have evaluated a novel in vitro cell-based human blood-brain barrier (BBB) model that could predict in vivo human brain penetration for compounds with different BBB permeabilities using the clinical positron emission tomography (PET) data. Comparison studies were also performed to demonstrate that the in vitro cell-based human BBB model resulted in better predictivity over the traditional permeability model in discovery organizations, Caco-2 cells. We evaluated the in vivo BBB permeability of [ 18 F] and [ 11 C]-compounds in humans by PET imaging. The in vivo plasma-brain exchange parameters used for comparison were determined in humans by PET using a kinetic analysis of the radiotracer binding. For each radiotracer, the parameters were determined by fitting the brain kinetics of the radiotracer using a two-tissue compartment model of the ligand-receptor interaction. Bidirectional transport studies with the same compounds as in in vivo studies were carried out using the in vitro cell-based human BBB model as well as Caco-2 cells. The in vitro cell-based human BBB model has important features of the BBB in vivo and is suitable for discriminating between CNS and non-CNS marketed drugs. A very good correlation (r 2 =0.90; P≤0.001) was demonstrated between in vitro BBB permeability and in vivo permeability coefficient. In contrast, a poor correlation (r 2 = 0.17) was obtained between Caco-2 data and in vivo human brain penetration. This study highlights the potential of this in vitro cell-based human BBB model in drug discovery and shows that it can be an extremely effective screening tool for CNS programs. (authors)

Impaired insulin action in the human brain: causes and metabolic consequences.

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Heni, Martin; Kullmann, Stephanie; Preissl, Hubert; Fritsche, Andreas; Häring, Hans-Ulrich

2015-12-01

Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism. However, brain imaging studies have revealed that not everybody responds equally to insulin and that a substantial number of people are brain insulin resistant. In this Review, we provide an overview of the effects of insulin in the brain in humans and the relevance of the effects for physiology. We present emerging evidence for insulin resistance of the human brain. Factors associated with brain insulin resistance such as obesity and increasing age, as well as possible pathogenic factors such as visceral fat, saturated fatty acids, alterations at the blood-brain barrier and certain genetic polymorphisms, are reviewed. In particular, the metabolic consequences of brain insulin resistance are discussed and possible future approaches to overcome brain insulin resistance and thereby prevent or treat obesity and type 2 diabetes mellitus are outlined.

Perioperative antibiotics in the setting of microvascular free tissue transfer: current practices

NARCIS (Netherlands)

Reiffel, Alyssa J.; Kamdar, Mehul R.; Kadouch, Daniel J. M.; Rohde, Christine H.; Spector, Jason A.

2010-01-01

Microvascular free tissue transfer is a ubiquitous and routine method of restoring anatomic defects. There is a paucity of data regarding the role of perioperative antibiotics in free tissue transfer. We designed a survey to explore usage patterns among microvascular surgeons and thereby define a

Interactions of the gasotransmitters contribute to microvascular tone (dysregulation in the preterm neonate.

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Rebecca M Dyson

Full Text Available Hydrogen sulphide (H2S, nitric oxide (NO, and carbon monoxide (CO are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow.90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO were determined through co-oximetry. NO was measured as nitrate and nitrite in urine. H2S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions.No relationship was observed between NO and CO (p = 0.18, r = 0.18. A positive relationship between NO and H2S (p = 0.008, r = 0.28 and an inverse relationship between CO and H2S (p = 0.01, r = -0.33 exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented.The relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may be based.

Engineering Microvascularized 3D Tissue Using Alginate-Chitosan Microcapsules.

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Zhang, Wujie; Choi, Jung K; He, Xiaoming

2017-02-01

Construction of vascularized tissues is one of the major challenges of tissue engineering. The goal of this study was to engineer 3D microvascular tissues by incorporating the HUVEC-CS cells with a collagen/alginate-chitosan (AC) microcapsule scaffold. In the presence of AC microcapsules, a 3D vascular-like network was clearly observable. The results indicated the importance of AC microcapsules in engineering microvascular tissues -- providing support and guiding alignment of HUVEC-CS cells. This approach provides an alternative and promising method for constructing vascularized tissues.

“Messing with the mind”: evolutionary challenges to human brain augmentation

OpenAIRE

Saniotis, Arthur; Henneberg, Maciej; Kumaratilake, Jaliya; Grantham, James P.

2014-01-01

The issue of brain augmentation has received considerable scientific attention over the last two decades. A key factor to brain augmentation that has been widely overlooked are the complex evolutionary processes which have taken place in evolving the human brain to its current state of functioning. Like other bodily organs, the human brain has been subject to the forces of biological adaptation. The structure and function of the brain, is very complex and only now we are beginning to understa...

The progress of radiosensitive genes of human brain glioma

International Nuclear Information System (INIS)

Wang Xi; Liu Qiang

2008-01-01

Human gliomas are one of the most aggressive tumors in brain which grow infiltrativly. Surgery is the mainstay of treatment. But as the tumor could not be entirely cut off, it is easy to relapse. Radiotherapy plays an important role for patients with gliomas after surgery. The efficacy of radiotherapy is associated with radio sensitivity of human gliomas. This paper makes a summary of current situation and progress for radiosensitive genes of human brain gliomas. (authors)

Cryptococcus neoformans-derived microvesicles enhance the pathogenesis of fungal brain infection.

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Sheng-He Huang

Full Text Available Cryptococcal meningoencephalitis is the most common fungal disease in the central nervous system. The mechanisms by which Cryptococcus neoformans invades the brain are largely unknown. In this study, we found that C. neoformans-derived microvesicles (CnMVs can enhance the traversal of the blood-brain barrier (BBB by C. neoformans invitro. The immunofluorescence imaging demonstrates that CnMVs can fuse with human brain microvascular endothelial cells (HBMECs, the constituents of the BBB. This activity is presumably due to the ability of the CnMVs to activate HBMEC membrane rafts and induce cell fusogenic activity. CnMVs also enhanced C. neoformans infection of the brain, found in both infected brains and cerebrospinal fluid. In infected mouse brains, CnMVs are distributed inside and around C. neoformans-induced cystic lesions. GFAP (glial fibrillary acidic protein-positive astrocytes were found surrounding the cystic lesions, overlapping with the 14-3-3-GFP (14-3-3-green fluorescence protein fusion signals. Substantial changes could be observed in areas that have a high density of CnMV staining. This is the first demonstration that C. neoformans-derived microvesicles can facilitate cryptococcal traversal across the BBB and accumulate at lesion sites of C. neoformans-infected brains. Results of this study suggested that CnMVs play an important role in the pathogenesis of cryptococcal meningoencephalitis.

Analysis of brain CT on 120 patients of human cysticercosis

International Nuclear Information System (INIS)

Ma, J.; To, R.; Ri, T.; Ra, S.; Inomata, Taiten; Ogawa, Yasuhiro; Maeda, Tomoo.

1990-01-01

A study on brain CT was made in 120 patients of human cysticercosis, which is a rare disease in Japan and clinical symptoms and laboratory data for the diagnosis were also discussed. From the point of therapeutic view, we proposed a new differentiation on brain CT of human cysticercosis, which is divided into two groups according to the alve or dead parasite. Furthermore, we proposed a new type named multiple large and small cysts type on brain CT. The idea of diagnostic standard was made integrating brain CT image, clinical symptoms and labolatory data. (author)

The human brain. Prenatal development and structure

International Nuclear Information System (INIS)

Marin-Padilla, Miguel

2011-01-01

This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

The human brain. Prenatal development and structure

Energy Technology Data Exchange (ETDEWEB)

Marin-Padilla, Miguel

2011-07-01

This book is unique among the current literature in that it systematically documents the prenatal structural development of the human brain. It is based on lifelong study using essentially a single staining procedure, the classic rapid Golgi procedure, which ensures an unusual and desirable uniformity in the observations. The book is amply illustrated with 81 large, high-quality color photomicrographs never previously reproduced. These photomicrographs, obtained at 6, 7, 11, 15, 18, 20, 25, 30, 35, and 40 weeks of gestation, offer a fascinating insight into the sequential prenatal development of neurons, blood vessels, and glia in the human brain. (orig.)

Evidence of native α-synuclein conformers in the human brain.

Science.gov (United States)

Gould, Neal; Mor, Danielle E; Lightfoot, Richard; Malkus, Kristen; Giasson, Benoit; Ischiropoulos, Harry

2014-03-14

α-Synuclein aggregation is central to the pathogenesis of several brain disorders. However, the native conformations and functions of this protein in the human brain are not precisely known. The native state of α-synuclein was probed by gel filtration coupled with native gradient gel separation, an array of antibodies with non-overlapping epitopes, and mass spectrometry. The existence of metastable conformers and stable monomer was revealed in the human brain.

Induction of complement proteins in a mouse model for cerebral microvascular Aβ deposition

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DeFilippis Kelly

2007-09-01

Full Text Available Abstract The deposition of amyloid β-protein (Aβ in cerebral vasculature, known as cerebral amyloid angiopathy (CAA, is a common pathological feature of Alzheimer's disease and related disorders. In familial forms of CAA single mutations in the Aβ peptide have been linked to the increase of vascular Aβ deposits accompanied by a strong localized activation of glial cells and elevated expression of neuroinflammatory mediators including complement proteins. We have developed human amyloid-β precursor protein transgenic mice harboring two CAA Aβ mutations (Dutch E693Q and Iowa D694N that mimic the prevalent cerebral microvascular Aβ deposition observed in those patients, and the Swedish mutations (K670N/M671L to increase Aβ production. In these Tg-SwDI mice, we have reported predominant fibrillar Aβ along microvessels in the thalamic region and diffuse plaques in cortical region. Concurrently, activated microglia and reactive astrocytes have been detected primarily in association with fibrillar cerebral microvascular Aβ in this model. Here we show that three native complement components in classical and alternative complement pathways, C1q, C3, and C4, are elevated in Tg-SwDI mice in regions rich in fibrillar microvascular Aβ. Immunohistochemical staining of all three proteins was increased in thalamus, hippocampus, and subiculum, but not frontal cortex. Western blot analysis showed significant increases of all three proteins in the thalamic region (with hippocampus as well as the cortical region, except C3 that was below detection level in cortex. Also, in the thalamic region (with hippocampus, C1q and C3 mRNAs were significantly up-regulated. These complement proteins appeared to be expressed largely by activated microglial cells associated with the fibrillar microvascular Aβ deposits. Our findings demonstrate that Tg-SwDI mice exhibit elevated complement protein expression in response to fibrillar vascular Aβ deposition that is

Sigma and opioid receptors in human brain tumors

Energy Technology Data Exchange (ETDEWEB)

Thomas, G.E.; Szuecs, M.; Mamone, J.Y.; Bem, W.T.; Rush, M.D.; Johnson, F.E.; Coscia, C.J. (St. Louis Univ. School of Medicine, MO (USA))

1990-01-01

Human brain tumors and nude mouse-borne human neuroblastomas and gliomas were analyzed for sigma and opioid receptor content. Sigma binding was assessed using ({sup 3}H) 1, 3-di-o-tolylguanidine (DTG), whereas opioid receptor subtypes were measured with tritiated forms of the following: {mu}, (D-ala{sup 2}, mePhe{sup 4}, gly-ol{sup 5}) enkephalin (DAMGE); {kappa}, ethylketocyclazocine (EKC) or U69,593; {delta}, (D-pen{sup 2}, D-pen{sup 5}) enkephalin (DPDPE) or (D-ala{sup 2}, D-leu{sup 5}) enkephalin (DADLE) with {mu} suppressor present. Binding parameters were estimated by homologous displacement assays followed by analysis using the LIGAND program. Sigma binding was detected in 15 of 16 tumors examined with very high levels found in a brain metastasis from an adenocarcinoma of lung and a human neuroblastoma (SK-N-MC) passaged in nude mice. {kappa} opioid receptor binding was detected in 4 of 4 glioblastoma multiforme specimens and 2 of 2 human astrocytoma cell lines tested but not in the other brain tumors analyzed.

Human astrocytes: structure and functions in the healthy brain.

Science.gov (United States)

Vasile, Flora; Dossi, Elena; Rouach, Nathalie

2017-07-01

Data collected on astrocytes' physiology in the rodent have placed them as key regulators of synaptic, neuronal, network, and cognitive functions. While these findings proved highly valuable for our awareness and appreciation of non-neuronal cell significance in brain physiology, early structural and phylogenic investigations of human astrocytes hinted at potentially different astrocytic properties. This idea sparked interest to replicate rodent-based studies on human samples, which have revealed an analogous but enhanced involvement of astrocytes in neuronal function of the human brain. Such evidence pointed to a central role of human astrocytes in sustaining more complex information processing. Here, we review the current state of our knowledge of human astrocytes regarding their structure, gene profile, and functions, highlighting the differences with rodent astrocytes. This recent insight is essential for assessment of the relevance of findings using animal models and for comprehending the functional significance of species-specific properties of astrocytes. Moreover, since dysfunctional astrocytes have been described in many brain disorders, a more thorough understanding of human-specific astrocytic properties is crucial for better-adapted translational applications.

Is endothelial microvascular function equally impaired among patients with chronic Chagas and ischemic cardiomyopathy?

Science.gov (United States)

Borges, Juliana Pereira; Mendes, Fernanda de Souza Nogueira Sardinha; Lopes, Gabriella de Oliveira; Sousa, Andréa Silvestre de; Mediano, Mauro Felippe Felix; Tibiriçá, Eduardo

2018-08-15

Chronic Chagas cardiomyopathy (CCC) and cardiomyopathies due to other etiologies involve differences in pathophysiological pathways that are still unclear. Systemic microvascular abnormalities are associated with the pathogenesis of ischemic heart disease. However, systemic microvascular endothelial function in CCC remains to be elucidated. Thus, we compared the microvascular endothelial function of patients presenting with CCC to those with ischemic cardiomyopathy disease. Microvascular reactivity was assessed in 21 patients with cardiomyopathy secondary to Chagas disease, 21 patients with cardiomyopathy secondary to ischemic disease and 21 healthy controls. Microvascular blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with iontophoresis of acetylcholine (ACh). Peak increase in forearm blood flow with ACh iontophoresis in relation to baseline was greater in healthy controls than in patients with heart disease (controls: 162.7 ± 58.4% vs. ischemic heart disease: 74.1 ± 48.3% and Chagas: 85.1 ± 68.1%; p < 0.0001). Patients with Chagas and ischemic cardiomyopathy presented similar ACh-induced changes from baseline in skin blood flow (p = 0.55). Endothelial microvascular function was equally impaired among patients with CCC and ischemic cardiomyopathy. Copyright © 2018 Elsevier B.V. All rights reserved.

Development of Human Brain Structural Networks Through Infancy and Childhood

Science.gov (United States)

Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J.; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

2015-01-01

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. PMID:24335033

Bovine brain ribonuclease is the functional homolog of human ribonuclease 1.

Science.gov (United States)

Eller, Chelcie H; Lomax, Jo E; Raines, Ronald T

2014-09-19

Mounting evidence suggests that human pancreatic ribonuclease (RNase 1) plays important roles in vivo, ranging from regulating blood clotting and inflammation to directly counteracting tumorigenic cells. Understanding these putative roles has been pursued with continual comparisons of human RNase 1 to bovine RNase A, an enzyme that appears to function primarily in the ruminant gut. Our results imply a different physiology for human RNase 1. We demonstrate distinct functional differences between human RNase 1 and bovine RNase A. Moreover, we characterize another RNase 1 homolog, bovine brain ribonuclease, and find pronounced similarities between that enzyme and human RNase 1. We report that human RNase 1 and bovine brain ribonuclease share high catalytic activity against double-stranded RNA substrates, a rare quality among ribonucleases. Both human RNase 1 and bovine brain RNase are readily endocytosed by mammalian cells, aided by tight interactions with cell surface glycans. Finally, we show that both human RNase 1 and bovine brain RNase are secreted from endothelial cells in a regulated manner, implying a potential role in vascular homeostasis. Our results suggest that brain ribonuclease, not RNase A, is the true bovine homolog of human RNase 1, and provide fundamental insight into the ancestral roles and functional adaptations of RNase 1 in mammals. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Microvascular oxygen pressure in the pig intestine during haemorrhagic shock and resuscitation

NARCIS (Netherlands)

Sinaasappel, M.; van Iterson, M.; Ince, C.

1999-01-01

1. The aim of this study was to investigate the relation between microvascular and venous oxygen pressures during haemorrhagic shock and resuscitation in the pig intestine. To this end microvascular PO2 (microPO2) was measured by quenching of Pd-porphyrin phosphorescence by oxygen and validated for

Common genetic variants influence human subcortical brain structures

NARCIS (Netherlands)

Hibar, D.P.; Stein, J.L.; Renteria, M.E.; Arias-Vasquez, A.; Desrivières, S.; Jahanshad, N.; Toro, R.; Wittfeld, K.; Abramovic, L.; Andersson, M.; Aribisala, B.S.; Armstrong, N.J.; Bernard, M.; Bohlken, M.M.; Biks, M.P.; Bralten, J.; Brown, A.A.; Chakravarty, M.M.; Chen, Q.; Ching, C.R.K.; Cuellar-Partida, G.; den Braber, A.; Giddaluru, S.; Goldman, A.L.; Grimm, O.; Guadalupe, T.; Hass, J.; Woldehawariat, G.; Holmes, A.J.; Hoogman, M.; Janowitz, D.; Jia, T.; Kim, S.; Klein, M.; Kraemer, B.; Lee, P.H.; Olde Loohuis, L.M.; Luciano, M.; Macare, C.; Mather, K.A.; Mattheisen, M.; Milaneschi, Y.; Nho, K.; Papmeyer, M.; Ramasamy, A.; Risacher, S.L.; Roiz-Santiañez, R.; Rose, E.J.; Salami, A.; Sämann, P.G.; Schmaal, L.; Schork, A.J.; Shin, J.; Strike, L.T.; Teumer, A.; Donkelaar, M.M.J.; van Eijk, K.R.; Walters, R.K.; Westlye, L.T.; Welan, C.D.; Winkler, A.M.; Zwiers, M.P.; Alhusaini, S.; Athanasiu, L.; Ehrlich, S.; Hakobjan, M.M.H.; Hartberg, C.B.; Haukvik, U.K.; Heister, A.J.G.A.M.; Hoehn, D.; Kasperaviciute, D.; Liewald, D.C.M.; Lopez, L.M.; Makkinje, R.R.; Matarin, M.; Naber, M.A.M.; Reese McKay, D.; Needham, M.; Nugent, A.C.; Pütz, B.; Royle, N.A.; Shen, L.; Sprooten, E.; Trabzuni, D.; van der Marel, S.S.L.; van Hulzen, K.J.E.; Walton, E.; Wolf, C.; Almasy, L.; Ames, D.; Arepalli, S.; Assareh, A.A.; Bastin, M.E.; Brodaty, H.; Bulayeva, K.B.; Carless, M.A.; Cichon, S.; Corvin, A.; Curran, J.E.; Czisch, M.; de Zubicaray, G.I.; Dillman, A.; Duggirala, R.; Dyer, T.D.; Erk, S.; Fedko, I.O.; Ferrucci, L.; Foroud, T.M.; Fox, P.T.; Fukunaga, M.; Gibbs, J.R.; Göring, H.H.H.; Green, R.C.; Guelfi, S.; Hansell, N.K.; Hartman, C.A.; Hegenscheid, K.; Heinz, A.; Hernandez, D.G.; Heslenfeld, D.J.; Hoekstra, P.J.; Holsboer, F.; Homuth, G.; Hottenga, J.J.; Ikeda, M.; Jack, C.R., Jr.; Jenkinson, M.; Johnson, R.; Kanai, R.; Keil, M.; Kent, J.W. Jr.; Kochunov, P.; Kwok, J.B.; Lawrie, S.M.; Liu, X.; Longo, D.L.; McMahon, K.L.; Meisenzahl, E.; Melle, I.; Mohnke, S.; Montgomery, G.W.; Mostert, J.C.; Mühleisen, T.W.; Nalls, M.A.; Nichols, T.E.; Nilsson, L.G.; Nöthen, M.M.; Ohi, K.; Olvera, R.L.; Perez-Iglesias, R.; Pike, G.B.; Potkin, S.G.; Reinvang, I.; Reppermund, S.; Rietschel, M.; Romanczuk-Seiferth, N.; Rosen, G.D.; Rujescu, D.; Schnell, K.; Schofield, P.R.; Smith, C.; Steen, V.M.; Sussmann, J.E.; Thalamuthu, A.; Toga, A.W.; Traynor, B.J.; Troncoso, J.; Turner, J.A.; Valdés Hernández, M.C.; van t Ent, D.; van der Brug, M.; van der Wee, N.J.A.; van Tol, M.J.; Veltman, D.J.; Wassink, T.H.; Westmann, E.; Zielke, R.H.; Zonderman, A.B.; Ashbrook, D.G.; Hager, R.; Lu, L.; McMahon, F.J.; Morris, D.W.; Williams, R.W.; Brunner, H.G.; Buckner, R.L.; Buitelaar, J.K.; Cahn, W.; Calhoun, V.D.; Cavalleri, G.L.; Crespo-Facorro, B.; Dale, A.M.; Davies, G.E.; Delanty, N.; Depondt, C.; Djurovic, S.; Drevets, W.C.; Espeseth, T.; Gollub, R.L.; Ho, B.C.; Hoffmann, W.; Hosten, N.; Kahn, R.S.; Le Hellard, S.; Meyer-Lindenberg, A.; Müller-Myhsok, B.; Nauck, M.; Nyberg, L.; Pandolfo, M.; Penninx, B.W.J.H.; Roffman, J.L.; Sisodiya, SM; Smoller, J.W.; van Bokhoven, H.; van Haren, N.E.M.; Völzke, H.; Walter, H.; Weiner, M.W.; Wen, W.; White, T.; Agartz, I.; Andreassen, O.A.; Blangero, J.; Boomsma, D.I.; Brouwer, R.M.; Cannon, D.M.; Cookson, M.R.; de Geus, E.J.C.; Deary, I.J.; Donohoe, G.; Fernandez, G.; Fisher, S.E.; Francks, C.; Glahn, D.C.; Grabe, H.J.; Gruber, O.; Hardy, J.; Hashimoto, R.; Hulshoff Pol, H.E.; Jönsson, E.G.; Kloszewska, I.; Lovestone, S.; Mattay, V.S.; Mecocci, P.; McDonald, C.; McIntosh, A.M.; Ophoff, R.A.; Paus, T.; Pausova, Z.; Ryten, M.; Sachdev, P.S.; Saykin, A.J.; Simmons, A.; Singleton, A.; Soininen, H.; Wardlaw, J.M.; Weale, M.E.; Weinberger, D.R.; Adams, H.H.H.; Launer, L.J.; Seiler, S.; Schmidt, R.; Chauhan, G.; Satizabal, C.L.; Becker, J.T.; Yanek, L.; van der Lee, S.J.; Ebling, M.; Fischl, B.; Longstreth, Jr. W.T.; Greve, D.; Schmidt, H.; Nyquist, P.; Vinke, L.N.; van Duijn, C.M.; Xue, L.; Mazoyer, B.; Bis, J.C.; Gudnason, V.; Seshadri, S.; Arfan Ikram, M.; Martin, N.G.; Wright, M.J.; Schumann, G.; Franke, B.; Thompson, P.M.; Medland, S.E.

2015-01-01

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common

Common genetic variants influence human subcortical brain structures

NARCIS (Netherlands)

D.P. Hibar (Derrek); J.L. Stein; M.E. Rentería (Miguel); A. Arias-Vásquez (Alejandro); S. Desrivières (Sylvane); N. Jahanshad (Neda); R. Toro (Roberto); K. Wittfeld (Katharina); L. Abramovic (Lucija); M. Andersson (Micael); B. Aribisala (Benjamin); N.J. Armstrong (Nicola J.); M. Bernard (Manon); M.M. Bohlken (Marc M.); M.P.M. Boks (Marco); L.B.C. Bralten (Linda); A.A. Brown (Andrew); M.M. Chakravarty (M. Mallar); Q. Chen (Qiang); C.R.K. Ching (Christopher); G. Cuellar-Partida (Gabriel); A. den Braber (Anouk); S. Giddaluru (Sudheer); A.L. Goldman (Aaron L.); O. Grimm (Oliver); T. Guadalupe (Tulio); J. Hass (Johanna); G. Woldehawariat (Girma); A.J. Holmes (Avram); M. Hoogman (Martine); D. Janowitz (Deborah); T. Jia (Tianye); S. Kim (Shinseog); M. Klein (Marieke); B. Kraemer (Bernd); P.H. Lee (Phil H.); L.M. Olde Loohuis (Loes M.); M. Luciano (Michelle); C. MacAre (Christine); R. Mather; M. Mattheisen (Manuel); Y. Milaneschi (Yuri); K. Nho (Kwangsik); M. Papmeyer (Martina); A. Ramasamy (Adaikalavan); S.L. Risacher (Shannon); R. Roiz-Santiañez (Roberto); E.J. Rose (Emma); A. Salami (Alireza); P.G. Sämann (Philipp); L. Schmaal (Lianne); N.J. Schork (Nicholas); J. Shin (Jean); L.T. Strike (Lachlan); A. Teumer (Alexander); M.M.J. Van Donkelaar (Marjolein M. J.); K.R. van Eijk (Kristel); R.K. Walters (Raymond); L.T. Westlye (Lars); C.D. Whelan (Christopher); A.M. Winkler (Anderson); M.P. Zwiers (Marcel); S. Alhusaini (Saud); L. Athanasiu (Lavinia); S.M. Ehrlich (Stefan); M. Hakobjan (Marina); C.B. Hartberg (Cecilie B.); U.K. Haukvik (Unn); A.J.G.A.M. Heister (Angelien J. G. A. M.); D. Hoehn (David); D. Kasperaviciute (Dalia); D.C. Liewald (David C.); L.M. Lopez (Lorna); R.R.R. Makkinje (Remco R. R.); M. Matarin (Mar); M.A.M. Naber (Marlies A. M.); D. Reese McKay; M. Needham (Margaret); A.C. Nugent (Allison); B. Pütz (Benno); N.A. Royle (Natalie); L. Shen (Li); R. Sprooten (Roy); D. Trabzuni (Danyah); S.S.L. Van Der Marel (Saskia S. L.); K.J.E. Van Hulzen (Kimm J. E.); E. Walton (Esther); A. Björnsson (Asgeir); L. Almasy (Laura); D.J. Ames (David); S. Arepalli (Sampath); A.A. Assareh; M.E. Bastin (Mark); H. Brodaty (Henry); K. Bulayeva (Kazima); M.A. Carless (Melanie); S. Cichon (Sven); A. Corvin (Aiden); J.E. Curran (Joanne); M. Czisch (Michael); G.I. de Zubicaray (Greig); A. Dillman (Allissa); A. Duggirala (Aparna); M.D. Dyer (Matthew); S. Erk; I. Fedko (Iryna); L. Ferrucci (Luigi); T. Foroud (Tatiana); P.T. Fox (Peter); M. Fukunaga (Masaki); J. Raphael Gibbs; H.H.H. Göring (Harald H.); R.C. Green (Robert C.); S. Guelfi (Sebastian); N.K. Hansell (Narelle); C.A. Hartman (Catharina); K. Hegenscheid (Katrin); J. Heinz (Judith); D.G. Hernandez (Dena); D.J. Heslenfeld (Dirk); P.J. Hoekstra (Pieter); F. Holsboer; G. Homuth (Georg); J.J. Hottenga (Jouke Jan); M. Ikeda (Masashi); C.R. Jack Jr. (Clifford); S. Jenkinson (Sarah); R. Johnson (Robert); R. Kanai (Ryota); M. Keil (Maria); J.W. Kent (Jack W.); P. Kochunov (Peter); J.B. Kwok (John B.); S. Lawrie (Stephen); X. Liu (Xinmin); D.L. Longo (Dan L.); K.L. Mcmahon (Katie); E. Meisenzahl (Eva); I. Melle (Ingrid); S. Mohnke (Sebastian); G.W. Montgomery (Grant); J.C. Mostert (Jeanette C.); T.W. Mühleisen (Thomas); M.A. Nalls (Michael); T.E. Nichols (Thomas); L.G. Nilsson; M.M. Nöthen (Markus); K. Ohi (Kazutaka); R.L. Olvera (Rene); R. Perez-Iglesias (Rocio); G. Bruce Pike; S.G. Potkin (Steven); I. Reinvang (Ivar); S. Reppermund; M. Rietschel (Marcella); N. Seiferth (Nina); G.D. Rosen (Glenn D.); D. Rujescu (Dan); K. Schnell (Kerry); C.J. Schofield (Christopher); C. Smith (Colin); V.M. Steen (Vidar); J. Sussmann (Jessika); A. Thalamuthu (Anbupalam); A.W. Toga (Arthur W.); B. Traynor (Bryan); J.C. Troncoso (Juan); J. Turner (Jessica); M.C. Valdés Hernández (Maria); D. van 't Ent (Dennis); M.P. van der Brug (Marcel); N.J. van der Wee (Nic); M.J.D. van Tol (Marie-José); D.J. Veltman (Dick); A.M.J. Wassink (Annemarie); E. Westman (Eric); R.H. Zielke (Ronald H.); A.B. Zonderman (Alan B.); D.G. Ashbrook (David G.); R. Hager (Reinmar); L. Lu (Lu); F.J. Mcmahon (Francis J); D.W. Morris (Derek W); R.W. Williams (Robert W.); H.G. Brunner; M. Buckner; J.K. Buitelaar (Jan K.); W. Cahn (Wiepke); V.D. Calhoun Vince D. (V.); G. Cavalleri (Gianpiero); B. Crespo-Facorro (Benedicto); A.M. Dale (Anders); G.E. Davies (Gareth); N. Delanty; C. Depondt (Chantal); S. Djurovic (Srdjan); D.A. Drevets (Douglas); T. Espeseth (Thomas); R.L. Gollub (Randy); B.C. Ho (Beng ); W. Hoffmann (Wolfgang); N. Hosten (Norbert); R. Kahn (René); S. Le Hellard (Stephanie); A. Meyer-Lindenberg; B. Müller-Myhsok (B.); M. Nauck (Matthias); L. Nyberg (Lars); M. Pandolfo (Massimo); B.W.J.H. Penninx (Brenda); J.L. Roffman (Joshua); S.M. Sisodiya (Sanjay); J.W. Smoller; H. van Bokhoven (Hans); N.E.M. van Haren (Neeltje E.); H. Völzke (Henry); H.J. Walter (Henrik); M.W. Weiner (Michael); W. Wen (Wei); T.J.H. White (Tonya); I. Agartz (Ingrid); O.A. Andreassen (Ole); J. Blangero (John); D.I. Boomsma (Dorret); R.M. Brouwer (Rachel); D.M. Cannon (Dara); M.R. Cookson (Mark); E.J.C. de Geus (Eco); I.J. Deary (Ian J.); D.J. Donohoe (Dennis); G. Fernandez (Guillén); S.E. Fisher (Simon); C. Francks (Clyde); D.C. Glahn (David); H.J. Grabe (Hans Jörgen); O. Gruber (Oliver); J. Hardy (John); R. Hashimoto (Ryota); H.E. Hulshoff Pol (Hilleke); E.G. Jönsson (Erik); I. Kloszewska (Iwona); S. Lovestone (Simon); V.S. Mattay (Venkata S.); P. Mecocci (Patrizia); C. McDonald (Colm); A.M. McIntosh (Andrew); R.A. Ophoff (Roel); T. Paus (Tomas); Z. Pausova (Zdenka); M. Ryten (Mina); P.S. Sachdev (Perminder); A.J. Saykin (Andrew); A. Simmons (Andrew); A. Singleton (Andrew); H. Soininen (H.); J.M. Wardlaw (J.); M.E. Weale (Michael); D.R. Weinberger (Daniel); H.H.H. Adams (Hieab); L.J. Launer (Lenore); S. Seiler (Stephan); R. Schmidt (Reinhold); G. Chauhan (Ganesh); C.L. Satizabal (Claudia L.); J.T. Becker (James); L.R. Yanek (Lisa); S.J. van der Lee (Sven); M. Ebling (Maritza); B. Fischl (Bruce); W.T. Longstreth Jr; D. Greve (Douglas); R. Schmidt (Reinhold); P. Nyquist (Paul); L.N. Vinke (Louis N.); C.M. van Duijn (Cornelia); L. Xue (Luting); B. Mazoyer (Bernard); J.C. Bis (Joshua); V. Gudnason (Vilmundur); S. Seshadri (Sudha); M.A. Ikram (Arfan); N.G. Martin (Nicholas); M.J. Wright (Margaret); G. Schumann (Gunter); B. Franke (Barbara); P.M. Thompson (Paul); S.E. Medland (Sarah Elizabeth)

2015-01-01

textabstractThe highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate

Transfer of Learning from Practicing Microvascular Anastomosis on Silastic Tubes to Rat Abdominal Aorta.

Science.gov (United States)

Mokhtari, Pooneh; Tayebi Meybodi, Ali; Lawton, Michael T; Payman, Andre; Benet, Arnau

2017-12-01

Learning to perform microvascular anastomosis is difficult. Laboratory practice models using artificial vessels are frequently used for this purpose. However, the efficacy of such practice models has not been objectively assessed for the performance of microvascular anastomosis during live surgical settings. This study was conducted to assess the transfer of learning from practicing microvascular anastomosis on tubes to anastomosing rat abdominal aorta. Ten surgeons without any experience in microvascular anastomosis were randomly assigned to an experimental or a control group. Both groups received didactic and visual training on end-to-end microvascular anastomosis. The experimental group received 24 sessions of hands-on training on microanastomosis using Silastic tubes. Next, both groups underwent recall tests on weeks 1, 2, and 8 after training. The recall test consisted of completing an end-to-end anastomosis on the rat's abdominal aorta. Anastomosis score, the time to complete the anastomosis, and the average time to place 1 stitch on the vessel perimeter were compared between the 2 groups. Compared with the control group, the experimental group did significantly better in terms of anastomosis score, total time, and per-stitch time. The measured variables showed stability and did not change significantly between the 3 recall tests. The skill of microvascular anastomosis is transferred from practicing on Silastic tubes to rat's abdominal aorta. Considering the relative advantages of Silastic tubes to live rodent surgeries, such as lower cost and absence of ethical issues, our results support the widespread use of Silastic tubes in training programs for microvascular anastomosis. Copyright © 2017 Elsevier Inc. All rights reserved.

COAGULATION PROFILE IN DIABETES MELLITUS AND ITS ASSOCIATION WITH MICROVASCULAR COMPLICATIONS

Directory of Open Access Journals (Sweden)

Uma Shankar Mishra

2017-12-01

Full Text Available BACKGROUND This study intends to assess the changes in the simple routine coagulation parameters in diabetes mellitus and to investigate whether any relationship exists among changes in these coagulation parameters and development of microvascular complication in diabetes mellitus. MATERIALS AND METHODS Period of study was from 2010-2012. It was done in M.K.C.G. Medical College with the approval from Berhampur University. It is a case control study. 50 diabetic patients and 50 age and sex matched non-diabetic patients were randomly selected. Simple coagulation parameters like Activated Partial Thromboplastin Time (aPTT, Prothrombin Time (PT, serum fibrinogen, platelet count and Plasminogen Activator Inhibitor-1 (PAI-1 were measured. Statistical study was done using unpaired t-test and analysis and calculations were done using GraphPad software. RESULTS Serum fibrinogen was found to be increased in diabetic patients when compared to non-diabetic patients (mean 278 ± 26.9 v/s 232.52 ± 16.5, P value - 0.009, significant. PAI-1 levels was found to be higher among the diabetics when compared to nondiabetics (47.64 ± 8.82 v/s 31.06 ± 7.12, the two-tailed P value is <0.0001, considered extremely significant. Platelet count through within normal limits. It was found to be decreased in diabetic patient when compared to non-diabetic (2.25 ± 0.18 v/s 2.33 ± 0.03, P value - 0.022. Prothrombin Time (PT (13.15 ± 0.52 v/s 13.04 ± 0.49, P value - 0.28 and PTT (33.04 ± 1.31 v/s 32.99 ± 1.29, P value 0.85, found to be statistically insignificant. Among 50 diabetic patients, 24 had neuropathy, 20 had nephropathy, 10 had retinopathy and 21 had none of these complications. On comparing diabetic patients with microvascular complications and without microvascular complications, significant age difference was observed (59.55 ± 5.06 v/s 51.00 ± 3.31, P=0.003. This probably was a reflection of increase in microvascular complications with increasing duration

Common genetic variants influence human subcortical brain structures

NARCIS (Netherlands)

Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivieres, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Loohuis, Loes M. Olde; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santianez, Roberto; Rose, Emma J.; Salami, Alireza; Saemann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Puetz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Goering, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzah, Eva; Melle, Ingrid; Mahnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Muehleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Noethen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdes Hernandez, Maria C.; van't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffman, Wolfgang; Hosten, Norbert; Kahn, Rene S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Mueller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Voelzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernandez, Guillen; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Pol, Hilleke E. Hulshoff; Joensson, Erik G.; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S.; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M.; Ophoff, Roel A.; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S.; Saykin, Andrew J.; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M.; Weale, Michael E.; Weinberger, Daniel R.; Adams, Hieab H. H.; Launer, Lenore J.; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L.; Becker, James T.; Yanek, Lisa; van der Lee, Sven J.; Ebling, Maritza; Fischl, Bruce; Longstreth, W. T.; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N.; van Duijn, Cornelia M.; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C.; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M. Arfan; Martin, Nicholas G.; Wright, Margaret J.; Schumann, Gunter; Franke, Barbara; Thompson, Paul M.; Medland, Sarah E.

2015-01-01

The highly complex structure of the human brain is strongly shaped by genetic influences(1). Subcortical brain regions form circuits with cortical areas to coordinate movement(2), learning, memory(3) and motivation(4), and altered circuits can lead to abnormal behaviour and disease(5). To

Impact of commercial cigarette smoke condensate on brain tissue co-cultured with astrocytes and blood-brain barrier endothelial cells.

Science.gov (United States)

Lee, Seon-Bong; Kim, Ju-Hyeong; Cho, Myung-Haing; Choe, Eun-Sang; Kim, Kwang-Sik; Shim, Soon-Mi

2017-01-01

The purpose of the current study was to investigate the effect of two commercial cigarette smoke condensates (CCSC) on oxidative stress and cell cytotoxicity in human brain (T98G) or astrocytes (U-373 MG) in the presence of human brain microvascular endothelial cells (HBMEC). Cell viability of mono-culture of T98G or U-373 MG was markedly decreased in a concentration-dependent manner, and T98G was more susceptible than U-373 MG to CCSC exposure. Cytotoxicity was less prominent when T98G was co-cultured with HBMEC than when T98G was co-cultured with U-373 MG. Significant reduction in trans-epithelial electric resistance (TEER), a biomarker of cellular integrity was noted in HBMEC co-cultured with T98G (HBMEC-T98G co-culture) and U-373 MG co-cultured with T98G (U-373 MG-T98G co-culture) after 24 or 48 hr CCSC exposure, respectively. TEER value of U-373 MG co-cultured with T98G (79-84%) was higher than HBMEC co-cultured with T98G (62-63%) within 120-hr incubation with CCSC. Reactive oxygen species (ROS) generated by CCSC in mono-culture of T98G and U-373 MG reached highest levels at 4 and 16 mg/ml, respectively. ROS production by T98G fell when co-cultured with HBMEC or U-373MG. These findings suggest that adverse consequences of CCSC treatment on brain cells may be protected by blood-brain barrier or astrocytes, but with chronic exposure toxicity may be worsened due to destruction of cellular integrity.

Default, Cognitive, and Affective Brain Networks in Human Tinnitus

Science.gov (United States)

2015-10-01

AWARD NUMBER: W81XWH-13-1-0491 TITLE: Default, Cognitive, and Affective Brain Networks in Human Tinnitus PRINCIPAL INVESTIGATOR: Jennifer R...SUBTITLE 5a. CONTRACT NUMBER Default, Cognitive and Affective Brain Networks in Human Tinnitus 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Tinnitus is a major health problem among those currently and formerly in military

Microvascular transplantation and replantation of the dog submandibular gland.

Science.gov (United States)

Su, Wan Fu; Jen, Yee Min; Chen, Shyi Gen; Nieh, Shin; Wang, Chih-Hung

2006-05-01

Transplantation and replantation of the submandibular gland with microvascular techniques were demonstrated in a previous study, with good gland survival. The application of radiation on the neck bed was attempted to address an actual clinical scenario in this study. Five canine submandibular glands were transplanted using microvascular techniques to the ipsilateral femoral system. Radiotherapy at a dosage level of 3,600 cGy using 600 cGy q.d was delivered to the nasopharyngeal and neck regions 2 weeks after transplantation. The transferred glands were then reintroduced into the original but radiated neck bed. The glands were harvested for histological examination 8 weeks later. Four of five canine submandibular glands can withstand microvascular transplantation and then replantation into a radiated neck bed for at least 8 weeks. However, the salivary function was depleted. The canine submandibular gland can survive the transplantation and replantation for at least 8 weeks in spite of precipitating radiation insult on the neck bed for 3 weeks. Neurorraphy is, however, essential to maintaining the glandular function.

Modulation of human dermal microvascular endothelial cell and human gingival fibroblast behavior by micropatterned silica coating surfaces for zirconia dental implant applications

International Nuclear Information System (INIS)

Laranjeira, Marta S; Carvalho, Ângela; Ferraz, Maria Pia; Monteiro, Fernando Jorge; Pelaez-Vargas, Alejandro; Hansford, Derek; Coimbra, Susana; Costa, Elísio; Santos-Silva, Alice; Fernandes, Maria Helena

2014-01-01

Dental ceramic implants have shown superior esthetic behavior and the absence of induced allergic disorders when compared to titanium implants. Zirconia may become a potential candidate to be used as an alternative to titanium dental implants if surface modifications are introduced. In this work, bioactive micropatterned silica coatings were produced on zirconia substrates, using a combined methodology of sol–gel processing and soft lithography. The aim of the work was to compare the in vitro behavior of human gingival fibroblasts (HGFs) and human dermal microvascular endothelial cells (HDMECs) on three types of silica-coated zirconia surfaces: flat and micropatterned (with pillars and with parallel grooves). Our results showed that cells had a higher metabolic activity (HGF, HDMEC) and increased gene expression levels of fibroblast-specific protein-1 (FSP-1) and collagen type I (COL I) on surfaces with pillars. Nevertheless, parallel grooved surfaces were able to guide cell growth. Even capillary tube-like networks of HDMEC were oriented according to the surface geometry. Zirconia and silica with different topographies have shown to be blood compatible and silica coating reduced bacteria adhesion. All together, the results indicated that microstructured bioactive coating seems to be an efficient strategy to improve soft tissue integration on zirconia implants, protecting implants from peri-implant inflammation and improving long-term implant stabilization. This new approach of micropatterned silica coating on zirconia substrates can generate promising novel dental implants, with surfaces that provide physical cues to guide cells and enhance their behavior. (paper)

Outer brain barriers in rat and human development

DEFF Research Database (Denmark)

Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

2015-01-01

Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

Genetic contributions to human brain morphology and intelligence

DEFF Research Database (Denmark)

Hulshoff Pol, HE; Schnack, HG; Posthuma, D

2006-01-01

Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology...... of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images...

Distribution of vesicular glutamate transporters in the human brain

Directory of Open Access Journals (Sweden)

Erika eVigneault

2015-03-01

Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

Gaze-and-brain-controlled interfaces for human-computer and human-robot interaction

Directory of Open Access Journals (Sweden)

Shishkin S. L.

2017-09-01

Full Text Available Background. Human-machine interaction technology has greatly evolved during the last decades, but manual and speech modalities remain single output channels with their typical constraints imposed by the motor system’s information transfer limits. Will brain-computer interfaces (BCIs and gaze-based control be able to convey human commands or even intentions to machines in the near future? We provide an overview of basic approaches in this new area of applied cognitive research. Objective. We test the hypothesis that the use of communication paradigms and a combination of eye tracking with unobtrusive forms of registering brain activity can improve human-machine interaction. Methods and Results. Three groups of ongoing experiments at the Kurchatov Institute are reported. First, we discuss the communicative nature of human-robot interaction, and approaches to building a more e cient technology. Specifically, “communicative” patterns of interaction can be based on joint attention paradigms from developmental psychology, including a mutual “eye-to-eye” exchange of looks between human and robot. Further, we provide an example of “eye mouse” superiority over the computer mouse, here in emulating the task of selecting a moving robot from a swarm. Finally, we demonstrate a passive, noninvasive BCI that uses EEG correlates of expectation. This may become an important lter to separate intentional gaze dwells from non-intentional ones. Conclusion. The current noninvasive BCIs are not well suited for human-robot interaction, and their performance, when they are employed by healthy users, is critically dependent on the impact of the gaze on selection of spatial locations. The new approaches discussed show a high potential for creating alternative output pathways for the human brain. When support from passive BCIs becomes mature, the hybrid technology of the eye-brain-computer (EBCI interface will have a chance to enable natural, fluent, and the

Higher cortical modulation of pain perception in the human brain: Psychological determinant.

Science.gov (United States)

Chen, Andrew Cn

2009-10-01

Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article examined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.

Development of human brain structural networks through infancy and childhood.

Science.gov (United States)

Huang, Hao; Shu, Ni; Mishra, Virendra; Jeon, Tina; Chalak, Lina; Wang, Zhiyue J; Rollins, Nancy; Gong, Gaolang; Cheng, Hua; Peng, Yun; Dong, Qi; He, Yong

2015-05-01

During human brain development through infancy and childhood, microstructural and macrostructural changes take place to reshape the brain's structural networks and better adapt them to sophisticated functional and cognitive requirements. However, structural topological configuration of the human brain during this specific development period is not well understood. In this study, diffusion magnetic resonance image (dMRI) of 25 neonates, 13 toddlers, and 25 preadolescents were acquired to characterize network dynamics at these 3 landmark cross-sectional ages during early childhood. dMRI tractography was used to construct human brain structural networks, and the underlying topological properties were quantified by graph-theory approaches. Modular organization and small-world attributes are evident at birth with several important topological metrics increasing monotonically during development. Most significant increases of regional nodes occur in the posterior cingulate cortex, which plays a pivotal role in the functional default mode network. Positive correlations exist between nodal efficiencies and fractional anisotropy of the white matter traced from these nodes, while correlation slopes vary among the brain regions. These results reveal substantial topological reorganization of human brain structural networks through infancy and childhood, which is likely to be the outcome of both heterogeneous strengthening of the major white matter tracts and pruning of other axonal fibers. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Magnetic resonance elastography of the brain: A comparison between pigs and humans.

Science.gov (United States)

Weickenmeier, Johannes; Kurt, Mehmet; Ozkaya, Efe; Wintermark, Max; Pauly, Kim Butts; Kuhl, Ellen

2018-01-01

Magnetic resonance elastography holds promise as a non-invasive, easy-to-use, in vivo biomarker for neurodegenerative diseases. Throughout the past decade, pigs have gained increased popularity as large animal models for human neurodegeneration. However, the volume of a pig brain is an order of magnitude smaller than the human brain, its skull is 40% thicker, and its head is about twice as big. This raises the question to which extent established vibration devices, actuation frequencies, and analysis tools for humans translate to large animal studies in pigs. Here we explored the feasibility of using human brain magnetic resonance elastography to characterize the dynamic properties of the porcine brain. In contrast to humans, where vibration devices induce an anterior-posterior displacement recorded in transverse sections, the porcine anatomy requires a dorsal-ventral displacement recorded in coronal sections. Within these settings, we applied a wide range of actuation frequencies, from 40Hz to 90Hz, and recorded the storage and loss moduli for human and porcine brains. Strikingly, we found that optimal actuation frequencies for humans translate one-to-one to pigs and reliably generate shear waves for elastographic post-processing. In a direct comparison, human and porcine storage and loss moduli followed similar trends and increased with increasing frequency. When translating these frequency-dependent storage and loss moduli into the frequency-independent stiffnesses and viscosities of a standard linear solid model, we found human values of μ 1 =1.3kPa, μ 2 =2.1kPa, and η=0.025kPas and porcine values of μ 1 =2.0kPa, μ 2 =4.9kPa, and η=0.046kPas. These results suggest that living human brain is softer and less viscous than dead porcine brain. Our study compares, for the first time, magnetic resonance elastography in human and porcine brains, and paves the way towards systematic interspecies comparison studies and ex vivo validation of magnetic resonance

The blood-brain barrier fatty acid transport protein 1 (FATP1/SLC27A1) supplies docosahexaenoic acid to the brain, and insulin facilitates transport.

Science.gov (United States)

Ochiai, Yusuke; Uchida, Yasuo; Ohtsuki, Sumio; Tachikawa, Masanori; Aizawa, Sanshiro; Terasaki, Tetsuya

2017-05-01

We purposed to clarify the contribution of fatty acid transport protein 1 (FATP1/SLC 27A1) to the supply of docosahexaenoic acid (DHA) to the brain across the blood-brain barrier in this study. Transport experiments showed that the uptake rate of [ 14 C]-DHA in human FATP1-expressing HEK293 cells was significantly greater than that in empty vector-transfected (mock) HEK293 cells. The steady-state intracellular DHA concentration was nearly 2-fold smaller in FATP1-expressing than in mock cells, suggesting that FATP1 works as not only an influx, but also an efflux transporter for DHA. [ 14 C]-DHA uptake by a human cerebral microvascular endothelial cell line (hCMEC/D3) increased in a time-dependent manner, and was inhibited by unlabeled DHA and a known FATP1 substrate, oleic acid. Knock-down of FATP1 in hCMEC/D3 cells with specific siRNA showed that FATP1-mediated uptake accounts for 59.2-73.0% of total [ 14 C]-DHA uptake by the cells. Insulin treatment for 30 min induced translocation of FATP1 protein to the plasma membrane in hCMEC/D3 cells and enhanced [ 14 C]-DHA uptake. Immunohistochemical analysis of mouse brain sections showed that FATP1 protein is preferentially localized at the basal membrane of brain microvessel endothelial cells. We found that two neuroprotective substances, taurine and biotin, in addition to DHA, undergo FATP1-mediated efflux. Overall, our results suggest that FATP1 localized at the basal membrane of brain microvessels contributes to the transport of DHA, taurine and biotin into the brain, and insulin rapidly increases DHA supply to the brain by promoting translocation of FATP1 to the membrane. Read the Editorial Comment for this article on page 324. © 2016 International Society for Neurochemistry.

Insulin action in the human brain: evidence from neuroimaging studies.

Science.gov (United States)

Kullmann, S; Heni, M; Fritsche, A; Preissl, H

2015-06-01

Thus far, little is known about the action of insulin in the human brain. Nonetheless, recent advances in modern neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), have made it possible to investigate the action of insulin in the brain in humans, providing new insights into the pathogenesis of brain insulin resistance and obesity. Using MEG, the clinical relevance of the action of insulin in the brain was first identified, linking cerebral insulin resistance with peripheral insulin resistance, genetic predisposition and weight loss success in obese adults. Although MEG is a suitable tool for measuring brain activity mainly in cortical areas, fMRI provides high spatial resolution for cortical as well as subcortical regions. Thus, the action of insulin can be detected within all eating behaviour relevant regions, which include regions deeply located within the brain, such as the hypothalamus, midbrain and brainstem, as well as regions within the striatum. In this review, we outline recent advances in the field of neuroimaging aiming to investigate the action of insulin in the human brain using different routes of insulin administration. fMRI studies have shown a significant insulin-induced attenuation predominantly in the occipital and prefrontal cortical regions and the hypothalamus, successfully localising insulin-sensitive brain regions in healthy, mostly normal-weight individuals. However, further studies are needed to localise brain areas affected by insulin resistance in obese individuals, which is an important prerequisite for selectively targeting brain insulin resistance in obesity. © 2015 British Society for Neuroendocrinology.

GM-CSF ameliorates microvascular barrier integrity via pericyte-derived Ang-1 in wound healing.

Science.gov (United States)

Yan, Min; Hu, Yange; Yao, Min; Bao, Shisan; Fang, Yong

2017-11-01

Skin wound healing involves complex coordinated interactions of cells, tissues, and mediators. Maintaining microvascular barrier integrity is one of the key events for endothelial homeostasis during wound healing. Vasodilation is observed after vasoconstriction, which causes blood vessels to become porous, facilitates leukocyte infiltration and aids angiogenesis at the wound-area, postinjury. Eventually, vessel integrity has to be reestablished for vascular maturation. Numerous studies have found that granulocyte macrophage colony-stimulating factor (GM-CSF) accelerates wound healing by inducing recruitment of repair cells into the injury area and releases of cytokines. However, whether GM-CSF is involving in the maintaining of microvascular barrier integrity and the underlying mechanism remain still unclear. Aim of this study was to investigate the effects of GM-CSF on modulation of microvascular permeability in wound healing and underlying mechanisms. Wound closure and microvascular leakage was investigated using a full-thickness skin wound mouse model after GM-CSF intervention. The endothelial permeability was measured by Evans blue assay in vivo and in vitro endothelium/pericyte co-culture system using a FITC-Dextran permeability assay. To identify the source of angiopoietin-1 (Ang-1), double staining is used in vivo and ELISA and qPCR are used in vitro. To determine the specific effect of Ang-1 on GM-CSF maintaining microvascular stabilization, Ang-1 siRNA was applied to inhibit Ang-1 production in vivo and in vitro. Wound closure was significantly accelerated and microvascular leakage was ameliorated after GM-CSF treatment in mouse wound sites. GM-CSF decreased endothelial permeability through tightening endothelial junctions and increased Ang-1 protein level that was derived by perictye. Furthermore, applications of siRNAAng-1 inhibited GM-CSF mediated protection of microvascular barrier integrity both in vivo and in vitro. Our data indicate that GM

Cyto- and receptor architectonic mapping of the human brain.

Science.gov (United States)

Palomero-Gallagher, Nicola; Zilles, Karl

2018-01-01

Mapping of the human brain is more than the generation of an atlas-based parcellation of brain regions using histologic or histochemical criteria. It is the attempt to provide a topographically informed model of the structural and functional organization of the brain. To achieve this goal a multimodal atlas of the detailed microscopic and neurochemical structure of the brain must be registered to a stereotaxic reference space or brain, which also serves as reference for topographic assignment of functional data, e.g., functional magnet resonance imaging, electroencephalography, or magnetoencephalography, as well as metabolic imaging, e.g., positron emission tomography. Although classic maps remain pioneering steps, they do not match recent concepts of the functional organization in many regions, and suffer from methodic drawbacks. This chapter provides a summary of the recent status of human brain mapping, which is based on multimodal approaches integrating results of quantitative cyto- and receptor architectonic studies with focus on the cerebral cortex in a widely used reference brain. Descriptions of the methods for observer-independent and statistically testable cytoarchitectonic parcellations, quantitative multireceptor mapping, and registration to the reference brain, including the concept of probability maps and a toolbox for using the maps in functional neuroimaging studies, are provided. Copyright © 2018 Elsevier B.V. All rights reserved.

A family of hyperelastic models for human brain tissue

Science.gov (United States)

Mihai, L. Angela; Budday, Silvia; Holzapfel, Gerhard A.; Kuhl, Ellen; Goriely, Alain

2017-09-01

Experiments on brain samples under multiaxial loading have shown that human brain tissue is both extremely soft when compared to other biological tissues and characterized by a peculiar elastic response under combined shear and compression/tension: there is a significant increase in shear stress with increasing axial compression compared to a moderate increase with increasing axial tension. Recent studies have revealed that many widely used constitutive models for soft biological tissues fail to capture this characteristic response. Here, guided by experiments of human brain tissue, we develop a family of modeling approaches that capture the elasticity of brain tissue under varying simple shear superposed on varying axial stretch by exploiting key observations about the behavior of the nonlinear shear modulus, which can be obtained directly from the experimental data.

Sensitivity analysis of human brain structural network construction

Directory of Open Access Journals (Sweden)

Kuang Wei

2017-12-01

Full Text Available Network neuroscience leverages diffusion-weighted magnetic resonance imaging and tractography to quantify structural connectivity of the human brain. However, scientists and practitioners lack a clear understanding of the effects of varying tractography parameters on the constructed structural networks. With diffusion images from the Human Connectome Project (HCP, we characterize how structural networks are impacted by the spatial resolution of brain atlases, total number of tractography streamlines, and grey matter dilation with various graph metrics. We demonstrate how injudicious combinations of highly refined brain parcellations and low numbers of streamlines may inadvertently lead to disconnected network models with isolated nodes. Furthermore, we provide solutions to significantly reduce the likelihood of generating disconnected networks. In addition, for different tractography parameters, we investigate the distributions of values taken by various graph metrics across the population of HCP subjects. Analyzing the ranks of individual subjects within the graph metric distributions, we find that the ranks of individuals are affected differently by atlas scale changes. Our work serves as a guideline for researchers to optimize the selection of tractography parameters and illustrates how biological characteristics of the brain derived in network neuroscience studies can be affected by the choice of atlas parcellation schemes. Diffusion tractography has been proven to be a promising noninvasive technique to study the network properties of the human brain. However, how various tractography and network construction parameters affect network properties has not been studied using a large cohort of high-quality data. We utilize data provided by the Human Connectome Project to characterize the changes to network properties induced by varying the brain parcellation atlas scales, the number of reconstructed tractography tracks, and the degree of grey

Dynamic Multi-Coil Shimming of the Human Brain at 7 Tesla

Science.gov (United States)

Juchem, Christoph; Nixon, Terence W.; McIntyre, Scott; Boer, Vincent O.; Rothman, Douglas L.; de Graaf, Robin A.

2011-01-01

High quality magnetic field homogenization of the human brain (i.e. shimming) for MR imaging and spectroscopy is a demanding task. The susceptibility differences between air and tissue are a longstanding problem as they induce complex field distortions in the prefrontal cortex and the temporal lobes. To date, the theoretical gains of high field MR have only been realized partially in the human brain due to limited magnetic field homogeneity. A novel shimming technique for the human brain is presented that is based on the combination of non-orthogonal basis fields from 48 individual, circular coils. Custom-built amplifier electronics enabled the dynamic application of the multi-coil shim fields in a slice-specific fashion. Dynamic multi-coil (DMC) shimming is shown to eliminate most of the magnetic field inhomogeneity apparent in the human brain at 7 Tesla and provided improved performance compared to state-of-the-art dynamic shim updating with zero through third order spherical harmonic functions. The novel technique paves the way for high field MR applications of the human brain for which excellent magnetic field homogeneity is a prerequisite. PMID:21824794

Free and microvascular bone grafting in the irradiated dog mandible

International Nuclear Information System (INIS)

Altobelli, D.E.; Lorente, C.A.; Handren, J.H. Jr.; Young, J.; Donoff, R.B.; May, J.W. Jr.

1987-01-01

Microvascular and free rib grafts were placed in 4.5 cm defects in an edentate mandibular body defect 18 to 28 days after completion of 50 Gy of irradiation from a 60 Co source. The animals were sacrificed from two to forty weeks postoperatively and evaluated clinically, radiographically, and histologically. There was a marked difference in the alveolar mucosal viability with the two grafts. Mucosal dehiscence was not observed over any of the microvascular grafts, but was present in seven-eighths of the free grafts. Union of the microvascular bone graft to the host bone occurred within six weeks. In contrast, after six weeks the free graft was sequestered in all the animals. An unexpected finding with both types of graft was the marked subperiosteal bone formation. This bone appeared to be derived from the host bed, stabilizing and bridging the defects bilaterally. The results suggest that radiated periosteum may play an important role in osteogenesis

Cross-hemispheric functional connectivity in the human fetal brain.

Science.gov (United States)

Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

2013-02-20

Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

Microvascular Anastomosis: Proposition of a Learning Curve.

Science.gov (United States)

Mokhtari, Pooneh; Tayebi Meybodi, Ali; Benet, Arnau; Lawton, Michael T

2018-04-14

Learning to perform a microvascular anastomosis is one of the most difficult tasks in cerebrovascular surgery. Previous studies offer little regarding the optimal protocols to maximize learning efficiency. This failure stems mainly from lack of knowledge about the learning curve of this task. To delineate this learning curve and provide information about its various features including acquisition, improvement, consistency, stability, and recall. Five neurosurgeons with an average surgical experience history of 5 yr and without any experience in bypass surgery performed microscopic anastomosis on progressively smaller-caliber silastic tubes (Biomet, Palm Beach Gardens, Florida) during 24 consecutive sessions. After a 1-, 2-, and 8-wk retention interval, they performed recall test on 0.7-mm silastic tubes. The anastomoses were rated based on anastomosis patency and presence of any leaks. Improvement rate was faster during initial sessions compared to the final practice sessions. Performance decline was observed in the first session of working on a smaller-caliber tube. However, this rapidly improved during the following sessions of practice. Temporary plateaus were seen in certain segments of the curve. The retention interval between the acquisition and recall phase did not cause a regression to the prepractice performance level. Learning the fine motor task of microvascular anastomosis adapts to the basic rules of learning such as the "power law of practice." Our results also support the improvement of performance during consecutive sessions of practice. The objective evidence provided may help in developing optimized learning protocols for microvascular anastomosis.

Brain structures in the sciences and humanities.

Science.gov (United States)

Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Sassa, Yuko; Kawashima, Ryuta

2015-11-01

The areas of academic interest (sciences or humanities) and area of study have been known to be associated with a number of factors associated with autistic traits. However, despite the vast amount of literature on the psychological and physiological characteristics associated with faculty membership, brain structural characteristics associated with faculty membership have never been investigated directly. In this study, we used voxel-based morphometry to investigate differences in regional gray matter volume (rGMV)/regional white matter volume (rWMV) between science and humanities students to test our hypotheses that brain structures previously robustly shown to be altered in autistic subjects are related to differences in faculty membership. We examined 312 science students (225 males and 87 females) and 179 humanities students (105 males and 74 females). Whole-brain analyses of covariance revealed that after controlling for age, sex, and total intracranial volume, the science students had significantly larger rGMV in an anatomical cluster around the medial prefrontal cortex and the frontopolar area, whereas the humanities students had significantly larger rWMV in an anatomical cluster mainly concentrated around the right hippocampus. These anatomical structures have been linked to autism in previous studies and may mediate cognitive functions that characterize differences in faculty membership. The present results may support the ideas that autistic traits and characteristics of the science students compared with the humanities students share certain characteristics from neuroimaging perspectives. This study improves our understanding of differences in faculty membership which is the link among cognition, biological factors, disorders, and education (academia).

Thrombin binding to human brain and spinal cord

International Nuclear Information System (INIS)

McKinney, M.; Snider, R.M.; Richelson, E.

1983-01-01

Thrombin, a serine protease that regulates hemostasis, has been shown to stimulate the formation of cGMP in murine neuroblastoma cells. The nervous system in vivo thus may be postulated to respond to this blood-borne factor after it breaches the blood-brain barrier, as in trauma. Human alpha-thrombin was radiolabeled with 125I and shown to bind rapidly, reversibly, and with high affinity to human brain and spinal cord. These findings indicate the presence of specific thrombin-binding sites in nervous tissue and may have important clinical implications

Mu opioid receptor binding sites in human brain

International Nuclear Information System (INIS)

Pilapil, C.; Welner, S.; Magnan, J.; Zamir, N.; Quirion, R.

1986-01-01

Our experiments focused on the examination of the distribution of mu opioid receptor binding sites in normal human brain using the highly selective ligand [ 3 H]DAGO, in both membrane binding assay and in vitro receptor autoradiography. Mu opioid binding sites are very discretely distributed in human brain with high densities of sites found in the posterior amygdala, caudate, putamen, hypothalamus and certain cortical areas. Moreover the autoradiographic distribution of [ 3 H]DAGO binding sites clearly reveals the discrete lamination (layers I and III-IV) of mu sites in cortical areas

Network Dynamics with BrainX3: A Large-Scale Simulation of the Human Brain Network with Real-Time Interaction

OpenAIRE

Xerxes D. Arsiwalla; Riccardo eZucca; Alberto eBetella; Enrique eMartinez; David eDalmazzo; Pedro eOmedas; Gustavo eDeco; Gustavo eDeco; Paul F.M.J. Verschure; Paul F.M.J. Verschure

2015-01-01

BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimula...

Network dynamics with BrainX3: a large-scale simulation of the human brain network with real-time interaction

OpenAIRE

Arsiwalla, Xerxes D.; Zucca, Riccardo; Betella, Alberto; Martínez, Enrique, 1961-; Dalmazzo, David; Omedas, Pedro; Deco, Gustavo; Verschure, Paul F. M. J.

2015-01-01

BrainX3 is a large-scale simulation of human brain activity with real-time interaction, rendered in 3D in a virtual reality environment, which combines computational power with human intuition for the exploration and analysis of complex dynamical networks. We ground this simulation on structural connectivity obtained from diffusion spectrum imaging data and model it on neuronal population dynamics. Users can interact with BrainX3 in real-time by perturbing brain regions with transient stimula...

Rate of evolution in brain-expressed genes in humans and other primates.

Directory of Open Access Journals (Sweden)

Hurng-Yi Wang

2007-02-01

Full Text Available Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM and then conducted three-way comparisons among (i mouse, OWM, and human, and (ii OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse, a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-à-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i faster evolution in gene expression, and (ii a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed.

Visual dictionaries as intermediate features in the human brain

Directory of Open Access Journals (Sweden)

Kandan eRamakrishnan

2015-01-01

Full Text Available The human visual system is assumed to transform low level visual features to object and scene representations via features of intermediate complexity. How the brain computationally represents intermediate features is still unclear. To further elucidate this, we compared the biologically plausible HMAX model and Bag of Words (BoW model from computer vision. Both these computational models use visual dictionaries, candidate features of intermediate complexity, to represent visual scenes, and the models have been proven effective in automatic object and scene recognition. These models however differ in the computation of visual dictionaries and pooling techniques. We investigated where in the brain and to what extent human fMRI responses to short video can be accounted for by multiple hierarchical levels of the HMAX and BoW models. Brain activity of 20 subjects obtained while viewing a short video clip was analyzed voxel-wise using a distance-based variation partitioning method. Results revealed that both HMAX and BoW explain a significant amount of brain activity in early visual regions V1, V2 and V3. However BoW exhibits more consistency across subjects in accounting for brain activity compared to HMAX. Furthermore, visual dictionary representations by HMAX and BoW explain significantly some brain activity in higher areas which are believed to process intermediate features. Overall our results indicate that, although both HMAX and BoW account for activity in the human visual system, the BoW seems to more faithfully represent neural responses in low and intermediate level visual areas of the brain.

Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling

DEFF Research Database (Denmark)

Sjøberg, Kim Anker; Frøsig, Christian; Kjøbsted, Rasmus

2017-01-01

and increased similarly in both legs during the clamp and L-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4...... and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand....

M3 receptor is involved in the effect of penehyclidine hydrochloride reduced endothelial injury in LPS-stimulated human pulmonary microvascular endothelial cell.

Science.gov (United States)

Yuan, Qinghong; Xiao, Fei; Liu, Qiangsheng; Zheng, Fei; Shen, Shiwen; He, Qianwen; Chen, Kai; Wang, Yanlin; Zhang, Zongze; Zhan, Jia

2018-02-01

LPS has been recently shown to induce muscarinic acetylcholine 3 receptor (M 3 receptor) expression and penehyclidine hydrochloride (PHC) is an anticholinergic drug which could block the expression of M 3 receptor. PHC has been demonstrated to perform protective effect on cell injury. This study is to investigate whether the effect of PHC on microvascular endothelial injury is related to its inhibition of M 3 receptor or not. HPMVECs were treated with specific M 3 receptor shRNA or PBS, and randomly divided into LPS group (A group), LPS+PHC group (B group), LPS + M 3 shRNA group (C group) and LPS + PHC + M 3 shRNA group (D group). Cells were collected at 60 min after LPS treatment to measure levels of LDH, endothelial permeability, TNF-α and IL-6 levels, NF-κB p65 activation, I-κB protein expression, p38MAPK, and ERK1/2 activations as well as M 3 mRNA expression. PHC could decrease LDH levels, cell permeability, TNF-α and IL-6 levels, p38 MAPK, ERK1/2, NF-κB p65 activations and M 3 mRNA expressions compared with LPS group. When M 3 receptor was silence, the changes of these indices were much more obvious. These findings suggest that M 3 receptor plays an important role in LPS-induced pulmonary microvascular endothelial injury, which is regulated through NF-κB p65 and MAPK activation. And knockout of M 3 receptor could attenuate LPS-induced pulmonary microvascular endothelial injury. Regulative effects of PHC on pulmonary microvascular permeability and NF-κB p65 as well as MAPK activations are including but not limited to inhibition of M 3 receptor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood-Brain Barrier.

Science.gov (United States)

Georgieva, Julia V; Hoekstra, Dick; Zuhorn, Inge S

2014-11-17

The blood-brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood-brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier-drug system ("Trojan horse complex") is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain.

The immune response of the human brain to abdominal surgery

DEFF Research Database (Denmark)

Forsberg, Anton; Cervenka, Simon; Jonsson Fagerlund, Malin

2017-01-01

OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans....... This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. METHODS: Eight males undergoing prostatectomy under general...... anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [11C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity...

Optogenetic control of human neurons in organotypic brain cultures

DEFF Research Database (Denmark)

Andersson, My; Avaliani, Natalia; Svensson, Andreas

2016-01-01

Optogenetics is one of the most powerful tools in neuroscience, allowing for selective control of specific neuronal populations in the brain of experimental animals, including mammals. We report, for the first time, the application of optogenetic tools to human brain tissue providing a proof......-of-concept for the use of optogenetics in neuromodulation of human cortical and hippocampal neurons as a possible tool to explore network mechanisms and develop future therapeutic strategies....

Centrality of Social Interaction in Human Brain Function.

Science.gov (United States)

Hari, Riitta; Henriksson, Linda; Malinen, Sanna; Parkkonen, Lauri

2015-10-07

People are embedded in social interaction that shapes their brains throughout lifetime. Instead of emerging from lower-level cognitive functions, social interaction could be the default mode via which humans communicate with their environment. Should this hypothesis be true, it would have profound implications on how we think about brain functions and how we dissect and simulate them. We suggest that the research on the brain basis of social cognition and interaction should move from passive spectator science to studies including engaged participants and simultaneous recordings from the brains of the interacting persons. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain activation during human male ejaculation

NARCIS (Netherlands)

Holstege, Ger; Georgiadis, Janniko R.; Paans, Anne M.J.; Meiners, Linda C.; Graaf, Ferdinand H.C.E. van der; Reinders, A.A.T.Simone

2003-01-01

Brain mechanisms that control human sexual behavior in general, and ejaculation in particular, are poorly understood. We used positron emission tomography to measure increases in regional cerebral blood flow (rCBF) during ejaculation compared with sexual stimulation in heterosexual male volunteers.

A psychology of the human brain-gut-microbiome axis.

Science.gov (United States)

Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

2017-04-01

In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

Directory of Open Access Journals (Sweden)

Maria Giovanna Scioli

Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

Data integration through brain atlasing: Human Brain Project tools and strategies.

Science.gov (United States)

Bjerke, Ingvild E; Øvsthus, Martin; Papp, Eszter A; Yates, Sharon C; Silvestri, Ludovico; Fiorilli, Julien; Pennartz, Cyriel M A; Pavone, Francesco S; Puchades, Maja A; Leergaard, Trygve B; Bjaalie, Jan G

2018-04-01

The Human Brain Project (HBP), an EU Flagship Initiative, is currently building an infrastructure that will allow integration of large amounts of heterogeneous neuroscience data. The ultimate goal of the project is to develop a unified multi-level understanding of the brain and its diseases, and beyond this to emulate the computational capabilities of the brain. Reference atlases of the brain are one of the key components in this infrastructure. Based on a new generation of three-dimensional (3D) reference atlases, new solutions for analyzing and integrating brain data are being developed. HBP will build services for spatial query and analysis of brain data comparable to current online services for geospatial data. The services will provide interactive access to a wide range of data types that have information about anatomical location tied to them. The 3D volumetric nature of the brain, however, introduces a new level of complexity that requires a range of tools for making use of and interacting with the atlases. With such new tools, neuroscience research groups will be able to connect their data to atlas space, share their data through online data systems, and search and find other relevant data through the same systems. This new approach partly replaces earlier attempts to organize research data based only on a set of semantic terminologies describing the brain and its subdivisions. Copyright © 2018 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Deconstructing Anger in the Human Brain.

Science.gov (United States)

Gilam, Gadi; Hendler, Talma

2017-01-01

Anger may be caused by a wide variety of triggers, and though it has negative consequences on health and well-being, it is also crucial in motivating to take action and approach rather than avoid a confrontation. While anger is considered a survival response inherent in all living creatures, humans are endowed with the mental flexibility that enables them to control and regulate their anger, and adapt it to socially accepted norms. Indeed, a profound interpersonal nature is apparent in most events which evoke anger among humans. Since anger consists of physiological, cognitive, subjective, and behavioral components, it is a contextualized multidimensional construct that poses theoretical and operational difficulties in defining it as a single psychobiological phenomenon. Although most neuroimaging studies have neglected the multidimensionality of anger and thus resulted in brain activations dispersed across the entire brain, there seems to be several reoccurring neural circuits subserving the subjective experience of human anger. Nevertheless, to capture the large variety in the forms and fashions in which anger is experienced, expressed, and regulated, and thus to better portray the related underlying neural substrates, neurobehavioral investigations of human anger should aim to further embed realistic social interactions within their anger induction paradigms.

Decade of the Brain 1990--2000: Maximizing human potential

Energy Technology Data Exchange (ETDEWEB)

1991-04-01

The US Decade of the Brain offers scientists throughout the Federal Government a unique opportunity to advance and apply scientific knowledge about the brain and nervous system. During the next 10 years, scientists hope to maximize human potential through studies of human behavior, senses and communication, learning and memory, genetic/chemical alterations, and environmental interactions. Progress in these areas should lead to reductions in mortality from brain and nervous system disorders and to improvements in the quality of life. This report identifies nine research areas that could form the basis of an integrated program in the brain and behavioral sciences. A chart summarizing the Federal activities in these nine areas may be found at the back of the report. In addition, three areas that span the nine research areas -- basic research, technology and international activities -- are considered.

Common genetic variants influence human subcortical brain structures.

Science.gov (United States)

Hibar, Derrek P; Stein, Jason L; Renteria, Miguel E; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S; Armstrong, Nicola J; Bernard, Manon; Bohlken, Marc M; Boks, Marco P; Bralten, Janita; Brown, Andrew A; Chakravarty, M Mallar; Chen, Qiang; Ching, Christopher R K; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H; Olde Loohuis, Loes M; Luciano, Michelle; Macare, Christine; Mather, Karen A; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L; Roiz-Santiañez, Roberto; Rose, Emma J; Salami, Alireza; Sämann, Philipp G; Schmaal, Lianne; Schork, Andrew J; Shin, Jean; Strike, Lachlan T; Teumer, Alexander; van Donkelaar, Marjolein M J; van Eijk, Kristel R; Walters, Raymond K; Westlye, Lars T; Whelan, Christopher D; Winkler, Anderson M; Zwiers, Marcel P; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M H; Hartberg, Cecilie B; Haukvik, Unn K; Heister, Angelien J G A M; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C M; Lopez, Lorna M; Makkinje, Remco R R; Matarin, Mar; Naber, Marlies A M; McKay, D Reese; Needham, Margaret; Nugent, Allison C; Pütz, Benno; Royle, Natalie A; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S L; van Hulzen, Kimm J E; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A; Bastin, Mark E; Brodaty, Henry; Bulayeva, Kazima B; Carless, Melanie A; Cichon, Sven; Corvin, Aiden; Curran, Joanne E; Czisch, Michael; de Zubicaray, Greig I; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D; Erk, Susanne; Fedko, Iryna O; Ferrucci, Luigi; Foroud, Tatiana M; Fox, Peter T; Fukunaga, Masaki; Gibbs, J Raphael; Göring, Harald H H; Green, Robert C; Guelfi, Sebastian; Hansell, Narelle K; Hartman, Catharina A; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G; Heslenfeld, Dirk J; Hoekstra, Pieter J; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W; Kochunov, Peter; Kwok, John B; Lawrie, Stephen M; Liu, Xinmin; Longo, Dan L; McMahon, Katie L; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W; Mostert, Jeanette C; Mühleisen, Thomas W; Nalls, Michael A; Nichols, Thomas E; Nilsson, Lars G; Nöthen, Markus M; Ohi, Kazutaka; Olvera, Rene L; Perez-Iglesias, Rocio; Pike, G Bruce; Potkin, Steven G; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D; Rujescu, Dan; Schnell, Knut; Schofield, Peter R; Smith, Colin; Steen, Vidar M; Sussmann, Jessika E; Thalamuthu, Anbupalam; Toga, Arthur W; Traynor, Bryan J; Troncoso, Juan; Turner, Jessica A; Valdés Hernández, Maria C; van 't Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J A; van Tol, Marie-Jose; Veltman, Dick J; Wassink, Thomas H; Westman, Eric; Zielke, Ronald H; Zonderman, Alan B; Ashbrook, David G; Hager, Reinmar; Lu, Lu; McMahon, Francis J; Morris, Derek W; Williams, Robert W; Brunner, Han G; Buckner, Randy L; Buitelaar, Jan K; Cahn, Wiepke; Calhoun, Vince D; Cavalleri, Gianpiero L; Crespo-Facorro, Benedicto; Dale, Anders M; Davies, Gareth E; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C; Espeseth, Thomas; Gollub, Randy L; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W J H; Roffman, Joshua L; Sisodiya, Sanjay M; Smoller, Jordan W; van Bokhoven, Hans; van Haren, Neeltje E M; Völzke, Henry; Walter, Henrik; Weiner, Michael W; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A; Blangero, John; Boomsma, Dorret I; Brouwer, Rachel M; Cannon, Dara M; Cookson, Mark R; de Geus, Eco J C; Deary, Ian J; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E; Francks, Clyde; Glahn, David C; Grabe, Hans J; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E; Jönsson, Erik G; Kloszewska, Iwona; Lovestone, Simon; Mattay, Venkata S; Mecocci, Patrizia; McDonald, Colm; McIntosh, Andrew M; Ophoff, Roel A; Paus, Tomas; Pausova, Zdenka; Ryten, Mina; Sachdev, Perminder S; Saykin, Andrew J; Simmons, Andy; Singleton, Andrew; Soininen, Hilkka; Wardlaw, Joanna M; Weale, Michael E; Weinberger, Daniel R; Adams, Hieab H H; Launer, Lenore J; Seiler, Stephan; Schmidt, Reinhold; Chauhan, Ganesh; Satizabal, Claudia L; Becker, James T; Yanek, Lisa; van der Lee, Sven J; Ebling, Maritza; Fischl, Bruce; Longstreth, W T; Greve, Douglas; Schmidt, Helena; Nyquist, Paul; Vinke, Louis N; van Duijn, Cornelia M; Xue, Luting; Mazoyer, Bernard; Bis, Joshua C; Gudnason, Vilmundur; Seshadri, Sudha; Ikram, M Arfan; Martin, Nicholas G; Wright, Margaret J; Schumann, Gunter; Franke, Barbara; Thompson, Paul M; Medland, Sarah E

2015-04-09

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System.

Science.gov (United States)

Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M; Svarer, Claus; Greve, Douglas N; Knudsen, Gitte M

2017-01-04

The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT 1A , 5-HT 1B , 5-HT 2A , and 5-HT 4 ) and the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of positron emission tomography (PET) and magnetic resonance imaging (MRI) scans acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain. We present a high-resolution positron emission tomography (PET)- and magnetic resonance imaging-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the serotonin (5-hydroxytryptamine, 5-HT) system. Next, we compared the regional receptor/transporter protein densities with mRNA levels and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system not only provides insight in the human brain's regional protein

Measuring dopamine release in the human brain with PET

Energy Technology Data Exchange (ETDEWEB)

Volkow, N.D. [Brookhaven National Lab., Upton, NY (United States)]|[State Univ. of New York at Stony Brook, Stony Brook, NY (United States). Dept. of Psychiatry; Fowler, J.S.; Logan, J.; Wang, G.J. [Brookhaven National Lab., Upton, NY (United States)

1995-12-01

The dopamine system is involved in the regulation of brain regions that subserve motor, cognitive and motivational behaviors. Disruptions of dopamine (DA) function have ben implicated in neurological and psychiatric illnesses including substance abuse as well as on some of the deficits associated with aging of the human brain. This has made the DA system an important topic in research in the neurosciences and neuroimaging as well as an important molecular target for drug development. Positron Emission Tomography (PET), was the first technology that enabled direct measurement of components of the DA system in the living human brain. Imaging studies of DA in the living brain have been indirect, relying on the development of radiotracers to label DA receptors, DA transporters, compounds which have specificity for the enzymes which degrade synaptic DA. Additionally, through the use of tracers that provide information on regional brain activity (ie brain glucose metabolism and cerebral blood flow) and of appropriate pharmacological interventions, it has been possible to assess the functional consequences of changes in brain DA activity. DA specific ligands have been useful in the evaluation of patients with neuropsychiatric illnesses as well as to investigate receptor blockade by antipsychotic drugs. A limitation of strategies that rely on the use of DA specific ligands is that the measures do not necessarily reflect the functional state of the dopaminergic system and that there use to study the effects of drugs is limited to the investigation of receptor or transporter occupancy. Newer strategies have been developed in an attempt to provide with information on dopamine release and on the functional responsivity of the DA system in the human brain. This in turn allows to investigate the effects of pharmacological agent in an analogous way to what is done with microdialysis techniques.

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System

DEFF Research Database (Denmark)

Beliveau, Vincent; Ganz-Benjaminsen, Melanie; Feng, Ling

2017-01-01

The serotonin (5-hydroxytryptamine, 5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. Here, we present a high-resolution, multidimensional, in vivo atlas of four of the human brain's 5-HT receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4...... with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (in picomoles per milliliter). We also assessed the regional association between protein concentration and mRNA expression in the human...... brain by comparing the 5-HT density across the atlas with data from the Allen Human Brain atlas and identified receptor- and transporter-specific associations that show the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system...

Microvascular function in pre-eclampsia is influenced by insulin resistance and an imbalance of angiogenic mediators.

Science.gov (United States)

Ghosh, Anshuman; Freestone, Nicholas S; Anim-Nyame, Nicholas; Arrigoni, Francesca I F

2017-04-01

In preeclampsia, maternal microvascular function is disrupted and angiogenesis is dysfunctional. Insulin resistance that occurs in some pregnancies also pathologically affects microvascular function. We wished to examine the relationship of angiogenic mediators and insulin resistance on microvascular health in pregnancy. We performed a nested, case-control study of 16 women who developed preeclampsia with 17 normal pregnant controls. We hypothesized that the impaired microvascular blood flow in preeclamptic women associated with an increased ratio of the antiangiogenic factors; (s-endoglin [sEng] and soluble fms-like tyrosine kinase-1 [sFlt-1]) and proangiogenic molecule (placental growth factor [PlGF]) could be influenced by insulin resistance. Serum samples taken after 28 weeks of gestation were measured for the angiogenic factors, insulin, and glucose alongside the inflammatory marker; tumor necrosis factor-α and endothelial activation, namely; soluble vascular cell adhesion molecule 1, intercellular adhesion molecule-1, and e-selectin. Maternal microvascular blood flow, measured by strain gauge plethysmography, correlated with ratios of pro- and antiangiogenic mediators independently of preeclampsia. Decreased microvascular function measured in preeclampsia strongly correlated with both the antiangiogenic factor (sFlt-1 + sEng): PlGF ratio and high levels of insulin resistance, and combining insulin resistance with antiangiogenic factor ratios further strengthened this relationship. In pregnancy, microvascular blood flow is strongly associated with perturbations in pro- and antiangiogenic mediators. In preeclampsia, the relationship of maternal microvascular dysfunction with antiangiogenic mediators is strengthened when combined with insulin resistance. © 2017 Kingston University. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Microvascular Remodeling and Wound Healing: A Role for Pericytes

Science.gov (United States)

Dulmovits, Brian M.; Herman, Ira M.

2012-01-01

Physiologic wound healing is highly dependent on the coordinated functions of vascular and non-vascular cells. Resolution of tissue injury involves coagulation, inflammation, formation of granulation tissue, remodeling and scarring. Angiogenesis, the growth of microvessels the size of capillaries, is crucial for these processes, delivering blood-borne cells, nutrients and oxygen to actively remodeling areas. Central to angiogenic induction and regulation is microvascular remodeling, which is dependent upon capillary endothelial cell and pericyte interactions. Despite our growing knowledge of pericyte-endothelial cell crosstalk, it is unclear how the interplay among pericytes, inflammatory cells, glia and connective tissue elements shape microvascular injury response. Here, we consider the relationships that pericytes form with the cellular effectors of healing in normal and diabetic environments, including repair following injury and vascular complications of diabetes, such as diabetic macular edema and proliferative diabetic retinopathy. In addition, pericytes and stem cells possessing “pericyte-like” characteristics are gaining considerable attention in experimental and clinical efforts aimed at promoting healing or eradicating ocular vascular proliferative disorders. As the origin, identification and characterization of microvascular pericyte progenitor populations remains somewhat ambiguous, the molecular markers, structural and functional characteristics of pericytes will be briefly reviewed. PMID:22750474

[Microvascular decompression for hemifacial spasm. Ten years of experience].

Science.gov (United States)

Revuelta-Gutiérrez, Rogelio; Vales-Hidalgo, Lourdes Olivia; Arvizu-Saldaña, Emiliano; Hinojosa-González, Ramón; Reyes-Moreno, Ignacio

2003-01-01

Hemifacial spasm characterized by involuntary paroxistic contractions of the face is more frequent on left side and in females. Evolution is progressive and in a few cases may disappear. Management includes medical treatment, botulinum toxin, and microvascular decompression of the nerve. We present the results of 116 microvascular decompressions performed in 88 patients over 10 years. All patients had previous medical treatment. All patients were operated on with microsurgical technique by asterional craniotomy. Vascular compression was present in all cases with one exception. Follow-up was from 1 month to 133 months. Were achieved excellent results in 70.45% of cases after first operation, good results in 9.09%, and poor results in 20.45% of patients. Long-term results were excellent in 81.82%, good in 6.82%, and poor in 11.36% of patients. Hypoacusia and transitory facial palsy were the main complications. Hemifacial spasm is a painless but disabling entity. Medical treatment is effective in a limited fashion. Injection of botulinum toxin has good response but benefit is transitory. Microvascular decompression is treatment of choice because it is minimally invasive, not destructive, requires minimum technical support, and yields best long-term results.

Patterns of differences in brain morphology in humans as compared to extant apes.

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Aldridge, Kristina

2011-01-01

Although human evolution is characterized by a vast increase in brain size, it is not clear whether or not certain regions of the brain are enlarged disproportionately in humans, or how this enlargement relates to differences in overall neural morphology. The aim of this study is to determine whether or not there are specific suites of features that distinguish the morphology of the human brain from that of apes. The study sample consists of whole brain, in vivo magnetic resonance images (MRIs) of anatomically modern humans (Homo sapiens sapiens) and five ape species (gibbons, orangutans, gorillas, chimpanzees, bonobos). Twenty-nine 3D landmarks, including surface and internal features of the brain were located on 3D MRI reconstructions of each individual using MEASURE software. Landmark coordinate data were scaled for differences in size and analyzed using Euclidean Distance Matrix Analysis (EDMA) to statistically compare the brains of each non-human ape species to the human sample. Results of analyses show both a pattern of brain morphology that is consistently different between all apes and humans, as well as patterns that differ among species. Further, both the consistent and species-specific patterns include cortical and subcortical features. The pattern that remains consistent across species indicates a morphological reorganization of 1) relationships between cortical and subcortical frontal structures, 2) expansion of the temporal lobe and location of the amygdala, and 3) expansion of the anterior parietal region. Additionally, results demonstrate that, although there is a pattern of morphology that uniquely defines the human brain, there are also patterns that uniquely differentiate human morphology from the morphology of each non-human ape species, indicating that reorganization of neural morphology occurred at the evolutionary divergence of each of these groups. Copyright © 2010 Elsevier Ltd. All rights reserved.

Spectroscopic microvascular blood detection from the endoscopically normal colonic mucosa: biomarker for neoplasia risk.

Science.gov (United States)

Roy, Hemant K; Gomes, Andrew; Turzhitsky, Vladimir; Goldberg, Michael J; Rogers, Jeremy; Ruderman, Sarah; Young, Kim L; Kromine, Alex; Brand, Randall E; Jameel, Mohammed; Vakil, Parmede; Hasabou, Nahla; Backman, Vadim

2008-10-01

We previously used a novel biomedical optics technology, 4-dimensional elastically scattered light fingerprinting, to show that in experimental colon carcinogenesis the predysplastic epithelial microvascular blood content is increased markedly. To assess the potential clinical translatability of this putative field effect marker, we characterized the early increase in blood supply (EIBS) in human beings in vivo. We developed a novel, endoscopically compatible, polarization-gated, spectroscopic probe that was capable of measuring oxygenated and deoxygenated (Dhb) hemoglobin specifically in the mucosal microcirculation through polarization gating. Microvascular blood content was measured in 222 patients from the endoscopically normal cecum, midtransverse colon, and rectum. If a polyp was present, readings were taken from the polyp tissue along with the normal mucosa 10-cm and 30-cm proximal and distal to the lesion. Tissue phantom studies showed that the probe had outstanding accuracy for hemoglobin determination (r(2) = 0.99). Augmentation of microvasculature blood content was most pronounced within the most superficial ( approximately 100 microm) layer and dissipated in deeper layers (ie, submucosa). EIBS was detectable within 30 cm from the lesion and the magnitude mirrored adenoma proximity. This occurred for both oxygenated hemoglobin and DHb, with the effect size being slightly greater for DHb. EIBS correlated with adenoma size and was not engendered by nonneoplastic (hyperplastic) polyps. We show, herein, that in vivo microvascular blood content can be measured and provides an accurate marker of field carcinogenesis. This technological/biological advance has numerous potential applications in colorectal cancer screening such as improved polyp detection and risk stratification.

Convergent transcriptional specializations in the brains of humans and song-learning birds

DEFF Research Database (Denmark)

Pfenning, Andreas R.; Hara, Erina; Whitney, Osceola

2014-01-01

Song-learning birds and humans share independently evolved similarities in brain pathways for vocal learning that are essential for song and speech and are not found in most other species. Comparisons of brain transcriptomes of song-learning birds and humans relative to vocal nonlearners identified...... convergent gene expression specializations in specific song and speech brain regions of avian vocal learners and humans. The strongest shared profiles relate bird motor and striatal song-learning nuclei, respectively, with human laryngeal motor cortex and parts of the striatum that control speech production...... and learning. Most of the associated genes function in motor control and brain connectivity. Thus, convergent behavior and neural connectivity for a complex trait are associated with convergent specialized expression of multiple genes....

Topological organization of the human brain functional connectome across the lifespan

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Miao Cao

2014-01-01

Full Text Available Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions. Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.

The Speculative Neuroscience of the Future Human Brain

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Robert A. Dielenberg

2013-05-01

Full Text Available The hallmark of our species is our ability to hybridize symbolic thinking with behavioral output. We began with the symmetrical hand axe around 1.7 mya and have progressed, slowly at first, then with greater rapidity, to producing increasingly more complex hybridized products. We now live in the age where our drive to hybridize has pushed us to the brink of a neuroscientific revolution, where for the first time we are in a position to willfully alter the brain and hence, our behavior and evolution. Nootropics, transcranial direct current stimulation (tDCS, transcranial magnetic stimulation (TMS, deep brain stimulation (DBS and invasive brain mind interface (BMI technology are allowing humans to treat previously inaccessible diseases as well as open up potential vistas for cognitive enhancement. In the future, the possibility exists for humans to hybridize with BMIs and mobile architectures. The notion of self is becoming increasingly extended. All of this to say: are we in control of our brains, or are they in control of us?

Brain Imaging of Human Sexual Response: Recent Developments and Future Directions.

Science.gov (United States)

Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Stable patterns of brain activation have been established for different phases of the sexual response, especially with regard to the wanting phase, and changes in these patterns can be linked to sexual response variations, including sexual dysfunctions. From this solid basis, connectivity studies of the human sexual response have begun to add a deeper understanding of the brain network function and structure involved. The study of "sexual" brain connectivity is still very young. Yet, by approaching the brain as a connected organ, the essence of brain function is captured much more accurately, increasing the likelihood of finding useful biomarkers and targets for intervention in sexual dysfunction.

The Brain Prize 2014: complex human functions.

Science.gov (United States)

Grigaityte, Kristina; Iacoboni, Marco

2014-11-01

Giacomo Rizzolatti, Stanislas Dehaene, and Trevor Robbins were recently awarded the 2014 Grete Lundbeck European Brain Research Prize for their 'pioneering research on higher brain mechanisms underpinning such complex human functions as literacy, numeracy, motivated behavior and social cognition, and for their effort to understand cognitive and behavioral disorders'. Why was their work highlighted? Is there anything that links together these seemingly disparate lines of research? Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of human endogenous retroviruses in brain development and function.

Science.gov (United States)

Mortelmans, Kristien; Wang-Johanning, Feng; Johanning, Gary L

2016-01-01

Endogenous retroviral sequences are spread throughout the genome of all humans, and make up about 8% of the genome. Despite their prevalence, the function of human endogenous retroviruses (HERVs) in humans is largely unknown. In this review we focus on the brain, and evaluate studies in animal models that address mechanisms of endogenous retrovirus activation in the brain and central nervous system (CNS). One such study in mice found that TRIM28, a protein critical for mouse early development, regulates transcription and silencing of endogenous retroviruses in neural progenitor cells. Another intriguing finding in human brain cells and mouse models was that endogenous retrovirus HERV-K appears to be protective against neurotoxins. We also report on studies that associate HERVs with human diseases of the brain and CNS. There is little doubt of an association between HERVs and a number of CNS diseases. However, a cause and effect relationship between HERVs and these diseases has not yet been established. © 2016 APMIS. Published by John Wiley & Sons Ltd.

Microvascular lesions of the true vocal fold.

Science.gov (United States)

Postma, G N; Courey, M S; Ossoff, R H

1998-06-01

Microvascular lesions, also called varices or capillary ectasias, in contrast to vocal fold polyps with telangiectatic vessels, are relatively small lesions arising from the microcirculation of the vocal fold. Varices are most commonly seen in female professional vocalists and may be secondary to repetitive trauma, hormonal variations, or repeated inflammation. Microvascular lesions may either be asymptomatic or cause frank dysphonia by interrupting the normal vibratory pattern, mass, or closure of the vocal folds. They may also lead to vocal fold hemorrhage, scarring, or polyp formation. Laryngovideostroboscopy is the key in determining the functional significance of vocal fold varices. Management of patients with a varix includes medical therapy, speech therapy, and occasionally surgical vaporization. Indications for surgery are recurrent hemorrhage, enlargement of the varix, development of a mass in conjunction with the varix or hemorrhage, and unacceptable dysphonia after maximal medical and speech therapy due to a functionally significant varix.

Three-dimensional morphology of the human embryonic brain

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N. Shiraishi

2015-09-01

Full Text Available The morphogenesis of the cerebral vesicles and ventricles was visualized in 3D movies using images derived from human embryo specimens between Carnegie stage 13 and 23 from the Kyoto Collection. These images were acquired with a magnetic resonance microscope equipped with a 2.35-T superconducting magnet. Three-dimensional images using the same scale demonstrated brain development and growth effectively. The non-uniform thickness of the brain tissue, which may indicate brain differentiation, was visualized with thickness-based surface color mapping. A closer view was obtained of the unique and complicated differentiation of the rhombencephalon, especially with regard to the internal view and thickening of the brain tissue. The present data contribute to a better understanding of brain and cerebral ventricle development.

Ex vivo MR volumetry of human brain hemispheres.

Science.gov (United States)

Kotrotsou, Aikaterini; Bennett, David A; Schneider, Julie A; Dawe, Robert J; Golak, Tom; Leurgans, Sue E; Yu, Lei; Arfanakis, Konstantinos

2014-01-01

The aims of this work were to (a) develop an approach for ex vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, (b) longitudinally assess regional brain volumes postmortem, and (c) investigate the relationship between MR volumetric measurements performed in vivo and ex vivo. An approach for ex vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex vivo was assessed. The relationship between in vivo and ex vivo volumetric measurements was investigated in seven elderly subjects imaged both antemortem and postmortem. This approach for ex vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than intersubject volume variation. A close linear correspondence was detected between in vivo and ex vivo volumetric measurements. Regional brain volumes measured with this approach for ex vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in vivo and ex vivo MR volumetric measurements suggests that this approach captures information linked to antemortem macrostructural brain characteristics. Copyright © 2013 Wiley Periodicals, Inc.

Preventing microvascular complications in type 1 diabetes mellitus

Science.gov (United States)

Viswanathan, Vijay

2015-01-01

Patients with complications of diabetes such as retinopathy, nephropathy, and cardiovascular complications have increased hospital stay with greater economic burden. Prevention of complications should be started before the onset of type 1 diabetes mellitus (T1DM) by working on risk factors and thereafter by intervention upon confirmatory diagnosis which can prevent further damage to β-cells. The actual risk of getting microvascular complications like microalbuminuria and retinopathy progression starts at glycated hemoglobin (HbA1c) level of 7%. As per the American Diabetes Association, a new pediatric glycemic control target of HbA1c 20 years as compared to patients <10 years of age. Screening of these complications should be done regularly, and appropriate preventive strategies should be followed. Angiotensin converting enzyme inhibitors and angiotensin II receptor blocker reduce progression from microalbuminuria to macroalbuminuria and increase the regression rate to normoalbuminuria. Diabetic microvascular complications can be controlled with tight glycemic therapy, dyslipidemia management and blood pressure control along with renal function monitoring, lifestyle changes, including smoking cessation and low-protein diet. An integrated and personalized care would reduce the risk of development of microvascular complications in T1DM patients. The child with diabetes who receives limited care is more likely to develop long-term complications at an earlier age. Screening for subclinical complications and early interventions with intensive therapy is the need of the hour. PMID:25941647

Injury Response of Resected Human Brain Tissue In Vitro

NARCIS (Netherlands)

Verwer, Ronald W. H.; Sluiter, Arja A.; Balesar, Rawien A.; Baaijen, Johannes C.; de Witt Hamer, Philip C.; Speijer, Dave; Li, Yichen; Swaab, Dick F.

2015-01-01

Brain injury affects a significant number of people each year. Organotypic cultures from resected normal neocortical tissue provide unique opportunities to study the cellular and neuropathological consequences of severe injury of adult human brain tissue in vitro. The in vitro injuries caused by

Amplification of a transcriptionally active DNA sequence in the human brain

International Nuclear Information System (INIS)

Yakovlev, A.G.; Sazonov, A.E.; Spunde, A.Ya.; Gindilis, V.M.

1986-01-01

The authors present their findings of tissue-specific amplification of a DNA fragment actively transcribed in the human brain. This genome fragment was found in the library complement of cDNA of the human brain and evidently belongs to a new class of moderate repetitions of DNA with an unstable copying capacity in the human genome. The authors isolated total cell RNA from various human tissues (brain, placenta), and rat tissues (brain, liver), by the method of hot phenol extraction with guanidine thiocynate. The poly(A + ) RNA fraction was isolated by chromatography. Synthesis of cDNA was done on a matrix of poly(A + ) RNA of human brain. The cDNA obtained was cloned in plasmid pBR322 for the PstI site using (dC/dG) sequences synthesized on the 3' ends of the vector molecule and cDNA respectively. In cloning 75 ng cDNA, the authors obtained approximately 10 5 recombinant. This library was analyzed by the hybridization method on columns with two radioactive ( 32 P) probes: the total cDNA preparation and the total nuclear DNA from the human brain. The number of copies of the cloned DNA fragment in the genome was determined by dot hybridization. Restricting fragments of human and rat DNA genomes homologous to the cloned cDNA were identified on radio-autographs. In each case, 10 micrograms of EcoRI DNA hydrolyzate was fractionated in 1% agarose gel. The probe was also readied with RNA samples fractionated in agarose gel with formaldehyde and transferred to a nitrocellulose filter under weak vacuum. The filter was hybridized with 0.1 micrograms DNA pAG 02, labeled with ( 32 P) to a specific activity of 0.5-1 x 10 9 counts/min x microgram. The autograph was exposed with amplifying screens at -70 0 C for 2 days

Puberty and structural brain development in humans.

Science.gov (United States)

Herting, Megan M; Sowell, Elizabeth R

2017-01-01

Adolescence is a transitional period of physical and behavioral development between childhood and adulthood. Puberty is a distinct period of sexual maturation that occurs during adolescence. Since the advent of magnetic resonance imaging (MRI), human studies have largely examined neurodevelopment in the context of age. A breadth of animal findings suggest that sex hormones continue to influence the brain beyond the prenatal period, with both organizational and activational effects occurring during puberty. Given the animal evidence, human MRI research has also set out to determine how puberty may influence otherwise known patterns of age-related neurodevelopment. Here we review structural-based MRI studies and show that pubertal maturation is a key variable to consider in elucidating sex- and individual- based differences in patterns of human brain development. We also highlight the continuing challenges faced, as well as future considerations, for this vital avenue of research. Copyright © 2016. Published by Elsevier Inc.

Quantifying anisotropy and fiber orientation in human brain histological sections

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Matthew D Budde

2013-02-01

Full Text Available Diffusion weighted imaging (DWI has provided unparalleled insight into the microscopic structure and organization of the central nervous system. Diffusion tensor imaging (DTI and other models of the diffusion MRI signal extract microstructural properties of tissues with relevance to the normal and injured brain. Despite the prevalence of such techniques and applications, accurate and large-scale validation has proven difficult, particularly in the human brain. In this report, human brain sections obtained from a digital public brain bank were employed to quantify anisotropy and fiber orientation using structure tensor analysis. The derived maps depict the intricate complexity of white matter fibers at a resolution not attainable with current DWI experiments. Moreover, the effects of multiple fiber bundles (i.e. crossing fibers and intravoxel fiber dispersion were demonstrated. Examination of the cortex and hippocampal regions validated specific features of previous in vivo and ex vivo DTI studies of the human brain. Despite the limitation to two dimensions, the resulting images provide a unique depiction of white matter organization at resolutions currently unattainable with DWI. The method of analysis may be used to validate tissue properties derived from DTI and alternative models of the diffusion signal.

Intrinsic functional brain architecture derived from graph theoretical analysis in the human fetus.

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Moriah E Thomason

Full Text Available The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA, our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks and older (GA≥31 weeks fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.

From Brain-Environment Connections to Temporal Dynamics and Social Interaction: Principles of Human Brain Function.

Science.gov (United States)

Hari, Riitta

2017-06-07

Experimental data about brain function accumulate faster than does our understanding of how the brain works. To tackle some general principles at the grain level of behavior, I start from the omnipresent brain-environment connection that forces regularities of the physical world to shape the brain. Based on top-down processing, added by sparse sensory information, people are able to form individual "caricature worlds," which are similar enough to be shared among other people and which allow quick and purposeful reactions to abrupt changes. Temporal dynamics and social interaction in natural environments serve as further essential organizing principles of human brain function. Copyright © 2017 Elsevier Inc. All rights reserved.

The association of systemic microvascular changes with lung function and lung density: a cross-sectional study.

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Bianca Harris

Full Text Available Smoking causes endothelial dysfunction and systemic microvascular disease with resultant end-organ damage in the kidneys, eyes and heart. Little is known about microvascular changes in smoking-related lung disease. We tested if microvascular changes in the retina, kidneys and heart were associated with obstructive spirometry and low lung density on computed tomography. The Multi-Ethnic Study of Atherosclerosis recruited participants age 45-84 years without clinical cardiovascular disease. Measures of microvascular function included retinal arteriolar and venular caliber, urine albumin-to-creatinine ratio and, in a subset, myocardial blood flow on magnetic resonance imaging. Spirometry was measured following ATS/ERS guidelines. Low attenuation areas (LAA were measured on lung fields of cardiac computed tomograms. Regression models adjusted for pulmonary and cardiac risk factors, medications and body size. Among 3,397 participants, retinal venular caliber was inversely associated with forced expiratory volume in one second (FEV(1 (P<0.001 and FEV(1/forced vital capacity (FVC ratio (P = 0.04. Albumin-to-creatinine ratio was inversely associated with FEV(1 (P = 0.002 but not FEV(1/FVC. Myocardial blood flow (n = 126 was associated with lower FEV(1 (P = 0.02, lower FEV(1/FVC (P = 0.001 and greater percentage LAA (P = 0.04. Associations were of greater magnitude among smokers. Low lung function was associated with microvascular changes in the retina, kidneys and heart, and low lung density was associated with impaired myocardial microvascular perfusion. These cross-sectional results suggest that microvascular damage with end-organ dysfunction in all circulations may pertain to the lung, that lung dysfunction may contribute to systemic microvascular disease, or that there may be a shared predisposition.

Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

Science.gov (United States)

Yu, Cai-Guo; Zhang, Ning; Yuan, Sha-Sha; Ma, Yan; Yang, Long-Yan; Feng, Ying-Mei; Zhao, Dong

2016-01-01

Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on "VEGF uncoupling with nitric oxide" and "competitive angiopoietin 1/angiopoietin 2" mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.

Regulation of Toll-like receptor 2 interaction with Ecgp96 controls Escherichia coli K1 invasion of brain endothelial cells

OpenAIRE

Krishnan, Subramanian; Chen, Shuang; Turcatel, Gianluca; Arditi, Moshe; Prasadarao, Nemani V.

2012-01-01

The interaction of outer membrane protein A (OmpA) with its receptor, Ecgp96 (a homologue of Hsp90β) is critical for the pathogenesis of E. coli K1 meningitis. Since Hsp90 chaperones Toll-like receptors (TLRs), we examined the role of TLRs in E. coli K1 infection. Herein, we show that newborn TLR2−/− mice are resistant to E. coli K1 meningitis, while TLR4−/− mice succumb to infection sooner. In vitro, OmpA+ E. coli infection selectively upregulates Ecgp96 and TLR2 in human brain microvascular...

Neuronal substrates of sensory gating within the human brain.

NARCIS (Netherlands)

Grunwald, T.; Boutros, N.N.; Pezer, N.; Oertzen, J. von; Fernandez, G.S.E.; Schaller, C.; Elger, C.E.

2003-01-01

BACKGROUND: For the human brain, habituation to irrelevant sensory input is an important function whose failure is associated with behavioral disturbances. Sensory gating can be studied by recording the brain's electrical responses to repeated clicks: the P50 potential is normally reduced to the

The effects of anti-obesity intervention with orlistat and sibutramine on microvascular endothelial function.

Science.gov (United States)

Al-Tahami, Belqes Abdullah Mohammad; Ismail, Ab Aziz Al-Safi; Bee, Yvonne Tee Get; Awang, Siti Azima; Salha Wan Abdul Rani, Wan Rimei; Sanip, Zulkefli; Rasool, Aida Hanum Ghulam

2015-01-01

Obesity is associated with impaired microvascular endothelial function. We aimed to determine the effects of orlistat and sibutramine treatment on microvascular endothelial function, anthropometric and lipid profile, blood pressure (BP), and heart rate (HR). 76 subjects were recruited and randomized to receive orlistat 120 mg three times daily or sibutramine 10 mg daily for 9 months. Baseline weight, BMI, BP, HR and lipid profile were taken. Microvascular endothelial function was assessed using laser Doppler fluximetry and iontophoresis process. Maximum change (max), percent change (% change) and peak flux (peak) in perfusion to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis were used to quantify endothelium dependent and independent vasodilatations. 24 subjects in both groups completed the trial. After treatment, weight and BMI were decreased for both groups. AChmax, ACh % change and ACh peak were increased in orlistat-treated group but no difference was observed for sibutramine-treated group. BP and total cholesterol (TC) were reduced for orlistat-treated group. HR was reduced for orlistat-treated group but was increased in sibutramine-treated group. 9 months treatment with orlistat significantly improved microvascular endothelial function. This was associated with reductions in weight, BMI, BP, HR, TC and low density lipoprotein cholesterol. No effect was seen in microvascular endothelial function with sibutramine.

[Neurological disorders and the blood-brain barrier. Strategies and limitations for drug delivery to the brain].

Science.gov (United States)

Domínguez, Alazne; Álvarez, Antonia; Suárez-Merino, Blanca; Goñi-de-Cerio, Felipe

2014-03-01

The incidence in the central nervous system diseases has increased with a growing elderly population. Unfortunately, conventional treatments used to treat the mentioned diseases are frequently ineffective due to the presence of the blood brain barrier. To illustrate the blood-brain barrier properties that limit drug transport into the brain and the main strategies employed to treat neurologic disorders. The blood-brain barrier is mainly composed of a specialized microvascular endothelium and of glial cells. It constitutes a valuable tool to separate the central nervous system from the rest of the body. Nevertheless, it also represents an obstacle to the delivery of therapeutic drugs to the brain. To be effective, drugs must reach their target in the brain. On one hand, therapeutic agents could be designed to be able to cross the blood brain barrier. On the other hand, drug delivery systems could be employed to facilitate the therapeutic agents' entry into the central nervous system. In vivo models of neurological diseases, in addition to in vitro models of the blood brain barrier, have been widely employed for the evaluation of drugs utilized to treat central nervous system diseases.

Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

DEFF Research Database (Denmark)

Sjøberg, Kim Anker; Rattigan, Stephen; Jeppesen, Jacob Fuglsbjerg

2015-01-01

Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether......-mediated glucose uptake in skeletal muscle by 90% (Prights...

Delineating Neural Structures of Developmental Human Brains with Diffusion Tensor Imaging

Directory of Open Access Journals (Sweden)

Hao Huang

2010-01-01

Full Text Available The human brain anatomy is characterized by dramatic structural changes during fetal development. It is extraordinarily complex and yet its origin is a simple tubular structure. Revealing detailed anatomy at different stages of brain development not only aids in understanding this highly ordered process, but also provides clues to detect abnormalities caused by genetic or environmental factors. However, anatomical studies of human brain development during the fetal period are surprisingly scarce and histology-based atlases have become available only recently. Diffusion tensor imaging (DTI measures water diffusion to delineate the underlying neural structures. The high contrasts derived from DTI can be used to establish the brain atlas. With DTI tractography, coherent neural structures, such as white matter tracts, can be three-dimensionally reconstructed. The primary eigenvector of the diffusion tensor can be further explored to characterize microstructures in the cerebral wall of the developmental brains. In this mini-review, the application of DTI in order to reveal the structures of developmental fetal brains has been reviewed in the above-mentioned aspects. The fetal brain DTI provides a unique insight for delineating the neural structures in both macroscopic and microscopic levels. The resultant DTI database will provide structural guidance for the developmental study of human fetal brains in basic neuroscience, and reference standards for diagnostic radiology of premature newborns.

Driving and driven architectures of directed small-world human brain functional networks.

Directory of Open Access Journals (Sweden)

Chaogan Yan

Full Text Available Recently, increasing attention has been focused on the investigation of the human brain connectome that describes the patterns of structural and functional connectivity networks of the human brain. Many studies of the human connectome have demonstrated that the brain network follows a small-world topology with an intrinsically cohesive modular structure and includes several network hubs in the medial parietal regions. However, most of these studies have only focused on undirected connections between regions in which the directions of information flow are not taken into account. How the brain regions causally influence each other and how the directed network of human brain is topologically organized remain largely unknown. Here, we applied linear multivariate Granger causality analysis (GCA and graph theoretical approaches to a resting-state functional MRI dataset with a large cohort of young healthy participants (n = 86 to explore connectivity patterns of the population-based whole-brain functional directed network. This directed brain network exhibited prominent small-world properties, which obviously improved previous results of functional MRI studies showing weak small-world properties in the directed brain networks in terms of a kernel-based GCA and individual analysis. This brain network also showed significant modular structures associated with 5 well known subsystems: fronto-parietal, visual, paralimbic/limbic, subcortical and primary systems. Importantly, we identified several driving hubs predominantly located in the components of the attentional network (e.g., the inferior frontal gyrus, supplementary motor area, insula and fusiform gyrus and several driven hubs predominantly located in the components of the default mode network (e.g., the precuneus, posterior cingulate gyrus, medial prefrontal cortex and inferior parietal lobule. Further split-half analyses indicated that our results were highly reproducible between two

[Construction of 2-dimensional tumor microvascular architecture phenotype in non-small cell lung cancer].

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Liu, Jin-kang; Wang, Xiao-yi; Xiong, Zeng; Zhou, Hui; Zhou, Jian-hua; Fu, Chun-yan; Li, Bo

2008-08-01

To construct a technological platform of 2-dimensional tumor microvascular architecture phenotype (2D-TAMP) expression. Thirty samples of non-small cell lung cancer (NSCLC) were collected after surgery. The corresponding sections of tumor tissue specimens to the slice of CT perfusion imaging were selected. Immunohistochemical staining,Gomori methenamine silver stain, and electron microscope observation were performed to build a technological platform of 2D-TMAP expression by detecting the morphology and the integrity of basement membrane of microvasculature, microvascular density, various microvascular subtype, the degree of the maturity and lumenization of microvasculature, and the characteristics of immunogenetics of microvasculature. The technological platform of 2D-TMAP expression was constructed successfully. There was heterogeneity in 2D-TMAP expression of non-small cell lung cancer. The microvascular of NSCLC had certain characteristics. 2D-TMAP is a key technology that can be used to observe the overall state of micro-environment in tumor growth.

Brain-Computer Interfaces Revolutionizing Human-Computer Interaction

CERN Document Server

Graimann, Bernhard; Allison, Brendan

2010-01-01

A brain-computer interface (BCI) establishes a direct output channel between the human brain and external devices. BCIs infer user intent via direct measures of brain activity and thus enable communication and control without movement. This book, authored by experts in the field, provides an accessible introduction to the neurophysiological and signal-processing background required for BCI, presents state-of-the-art non-invasive and invasive approaches, gives an overview of current hardware and software solutions, and reviews the most interesting as well as new, emerging BCI applications. The book is intended not only for students and young researchers, but also for newcomers and other readers from diverse backgrounds keen to learn about this vital scientific endeavour.

[Isolation and identification of brain tumor stem cells from human brain neuroepithelial tumors].

Science.gov (United States)

Fang, Jia-sheng; Deng, Yong-wen; Li, Ming-chu; Chen, Feng-Hua; Wang, Yan-jin; Lu, Ming; Fang, Fang; Wu, Jun; Yang, Zhuan-yi; Zhou, Xang-yang; Wang, Fei; Chen, Cheng

2007-01-30

To establish a simplified culture system for the isolation of brain tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to observe the growth and differentiation pattern of BTSCs, and to investigate their expression of the specific markers. Twenty-six patients with brain neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues were taken from each tumor to be dissociated, triturated into single cells in sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium simply supplemented with B27, human basic fibroblast growth factor (20 microg/L), human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine, penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were generated, they were triturated again and passed in fresh medium. Limiting dilution assay was performed to observe the monoclone formation. 5-bromodeoxyuridine (BrdU) incorporation test was performed to observe the proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium supplemented with 10% fetal bovine serum to observe their differentiation. Immunocytochemistry was used to examine the expression of CD133 and nestin, specific markers of BTSC, and the rate of CD133 positive cells. Only a minority of subsets of cells from the tumors of neuroepithelial tissue had the capacity to survive, proliferate, and generate free-floating neurosphere-like BTSs in the simplified serum-free medium. These cells attached to the poly-L-lysine coated coverslips in the serum-supplemented medium and differentiated. The BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. A new simplified culture system for the isolation of BTSCs is established. The tumors of human neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which can be isolated

Long-term neuroglobin expression of human astrocytes following brain trauma.

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Chen, Xiameng; Liu, Yuan; Zhang, Lin; Zhu, Peng; Zhu, Haibiao; Yang, Yu; Guan, Peng

2015-10-08

Neuroglobin (Ngb), a 17 kDa monomeric protein, was initially described as a vertebrate oxygen-binding heme protein in 2000 and detected in metabolically active organs or cells, like the brain, peripheral nervous system as well as certain endocrine cells. A large array of initial experimental work reported that Ngb displayed a neuron restricted expression pattern in mammalian brains. However, growing evidence indicated astrocytes may also express Ngb under pathological conditions. To address the question whether human astrocytes express Ngb under traumatic insults, we investigated Ngb immuno-reactivity in post-mortem human brain tissues that died of acute, sub-acute and chronic brain trauma, respectively. We observed astrocytic Ngb expression in sub-acute and chronic traumatic brains rather than acute traumatic brains. Strikingly, the Ngb immuno-reactive astrocytes were still strongly detectable in groups that died 12 months after brain trauma. Our findings may imply an unexplored role of Ngb in astrocytes and the involved mechanisms were suggested to be further characterized. Also, therapeutic application of Ngb or Ngb-inducible chemical compounds in neuro-genesis or astrocytic scar forming can be expected. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Diabetes : Brain changes in T1DM—a microvascular complication?

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Biessels, Geert Jan

2015-01-01

A recent study indicates that type 1 diabetes mellitus is associated with vascular brain lesions that affect cognition and might represent a target for preventive measures. This commentary discusses methods to ascertain vascular contributions to cerebral dysfunction in diabetes mellitus and

Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

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Qiu, Zilong; Li, Xiao

2017-04-01

Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

Lactate fuels the human brain during exercise

DEFF Research Database (Denmark)

Quistorff, Bjørn; Secher, Niels H; Van Lieshout, Johannes J

2008-01-01

The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up......)] from a resting value of 6 to exercise, cerebral activation associated with mental activity, or exposure to a stressful situation. The CMR decrease is prevented with combined beta(1)- and beta(2)-adrenergic receptor...

Pathways for insulin access to the brain: the role of the microvascular endothelial cell

OpenAIRE

Meijer, Rick I.; Gray, Sarah M.; Aylor, Kevin W.; Barrett, Eugene J.

2016-01-01

New understanding of the directional flow of subarachnoid cerebrospinal fluid (CSF) through the Virchow-Robin space (VRS) to brain parenchyma, coupled with the demonstration here of rapid, insulin receptor-dependent trapping of plasma insulin by the brain microvasculature, underscores the direct role of insulin's blood-brain barrier transit to insulin delivery to the brain.

Cell proliferation along vascular islands during microvascular network growth

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Kelly-Goss Molly R

2012-06-01

Full Text Available Abstract Background Observations in our laboratory provide evidence of vascular islands, defined as disconnected endothelial cell segments, in the adult microcirculation. The objective of this study was to determine if vascular islands are involved in angiogenesis during microvascular network growth. Results Mesenteric tissues, which allow visualization of entire microvascular networks at a single cell level, were harvested from unstimulated adult male Wistar rats and Wistar rats 3 and 10 days post angiogenesis stimulation by mast cell degranulation with compound 48/80. Tissues were immunolabeled for PECAM and BRDU. Identification of vessel lumens via injection of FITC-dextran confirmed that endothelial cell segments were disconnected from nearby patent networks. Stimulated networks displayed increases in vascular area, length density, and capillary sprouting. On day 3, the percentage of islands with at least one BRDU-positive cell increased compared to the unstimulated level and was equal to the percentage of capillary sprouts with at least one BRDU-positive cell. At day 10, the number of vascular islands per vascular area dramatically decreased compared to unstimulated and day 3 levels. Conclusions These results show that vascular islands have the ability to proliferate and suggest that they are able to incorporate into the microcirculation during the initial stages of microvascular network growth.

Dietary sodium loading impairs microvascular function independent of blood pressure in humans: role of oxidative stress

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Greaney, Jody L; DuPont, Jennifer J; Lennon-Edwards, Shannon L; Sanders, Paul W; Edwards, David G; Farquhar, William B

2012-01-01

Animal studies have reported dietary salt-induced reductions in vascular function independent of increases in blood pressure (BP). The purpose of this study was to determine if short-term dietary sodium loading impairs cutaneous microvascular function in normotensive adults with salt resistance. Following a control run-in diet, 12 normotensive adults (31 ± 2 years) were randomized to a 7 day low-sodium (LS; 20 mmol day−1) and 7 day high-sodium (HS; 350 mmol day−1) diet (controlled feeding study). Salt resistance, defined as a ≤5 mmHg change in 24 h mean BP determined while on the LS and HS diets, was confirmed in all subjects undergoing study (LS: 84 ± 1 mmHg vs. HS: 85 ± 2 mmHg; P > 0.05). On the last day of each diet, subjects were instrumented with two microdialysis fibres for the local delivery of Ringer solution and 20 mm ascorbic acid (AA). Laser Doppler flowmetry was used to measure red blood cell flux during local heating-induced vasodilatation (42°C). After the established plateau, 10 mm l-NAME was perfused to quantify NO-dependent vasodilatation. All data were expressed as a percentage of maximal cutaneous vascular conductance (CVC) at each site (28 mm sodium nitroprusside; 43°C). Sodium excretion increased during the HS diet (P sodium loading impairs cutaneous microvascular function independent of BP in normotensive adults and suggest a role for oxidative stress. PMID:22907057

Brain and Social Networks: Fundamental Building Blocks of Human Experience.

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Falk, Emily B; Bassett, Danielle S

2017-09-01

How do brains shape social networks, and how do social ties shape the brain? Social networks are complex webs by which ideas spread among people. Brains comprise webs by which information is processed and transmitted among neural units. While brain activity and structure offer biological mechanisms for human behaviors, social networks offer external inducers or modulators of those behaviors. Together, these two axes represent fundamental contributors to human experience. Integrating foundational knowledge from social and developmental psychology and sociology on how individuals function within dyads, groups, and societies with recent advances in network neuroscience can offer new insights into both domains. Here, we use the example of how ideas and behaviors spread to illustrate the potential of multilayer network models. Copyright © 2017 Elsevier Ltd. All rights reserved.

Kisspeptin modulates sexual and emotional brain processing in humans.

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Comninos, Alexander N; Wall, Matthew B; Demetriou, Lysia; Shah, Amar J; Clarke, Sophie A; Narayanaswamy, Shakunthala; Nesbitt, Alexander; Izzi-Engbeaya, Chioma; Prague, Julia K; Abbara, Ali; Ratnasabapathy, Risheka; Salem, Victoria; Nijher, Gurjinder M; Jayasena, Channa N; Tanner, Mark; Bassett, Paul; Mehta, Amrish; Rabiner, Eugenii A; Hönigsperger, Christoph; Silva, Meire Ribeiro; Brandtzaeg, Ole Kristian; Lundanes, Elsa; Wilson, Steven Ray; Brown, Rachel C; Thomas, Sarah A; Bloom, Stephen R; Dhillo, Waljit S

2017-02-01

Sex, emotion, and reproduction are fundamental and tightly entwined aspects of human behavior. At a population level in humans, both the desire for sexual stimulation and the desire to bond with a partner are important precursors to reproduction. However, the relationships between these processes are incompletely understood. The limbic brain system has key roles in sexual and emotional behaviors, and is a likely candidate system for the integration of behavior with the hormonal reproductive axis. We investigated the effects of kisspeptin, a recently identified key reproductive hormone, on limbic brain activity and behavior. Using a combination of functional neuroimaging and hormonal and psychometric analyses, we compared the effects of kisspeptin versus vehicle administration in 29 healthy heterosexual young men. We demonstrated that kisspeptin administration enhanced limbic brain activity specifically in response to sexual and couple-bonding stimuli. Furthermore, kisspeptin's enhancement of limbic brain structures correlated with psychometric measures of reward, drive, mood, and sexual aversion, providing functional significance. In addition, kisspeptin administration attenuated negative mood. Collectively, our data provide evidence of an undescribed role for kisspeptin in integrating sexual and emotional brain processing with reproduction in humans. These results have important implications for our understanding of reproductive biology and are highly relevant to the current pharmacological development of kisspeptin as a potential therapeutic agent for patients with common disorders of reproductive function. National Institute for Health Research (NIHR), Wellcome Trust (Ref 080268), and the Medical Research Council (MRC).

Ex-vivo MR Volumetry of Human Brain Hemispheres

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Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

2013-01-01

Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

mRNA Transcriptomics of Galectins Unveils Heterogeneous Organization in Mouse and Human Brain

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Sebastian John

2016-12-01

Full Text Available Background: Galectins, a family of non-classically secreted, β-galactoside binding proteins is involved in several brain disorders; however no systematic knowledge on the normal neuroanatomical distribution and functions of galectins exits. Hence, the major purpose of this study was to understand spatial distribution and predict functions of galectins in brain and also compare the degree of conservation vs. divergence between mouse and human species. The latter objective was required to determine the relevance and appropriateness of studying galectins in mouse brain which may ultimately enable us to extrapolate the findings to human brain physiology and pathologies.Results: In order to fill this crucial gap in our understanding of brain galectins, we analyzed the in situ hybridization (ISH and microarray data of adult mouse and human brain respectively, from the Allen Brain Atlas, to resolve each galectin-subtype’s spatial distribution across brain distinct cytoarchitecture. Next, transcription factors (TFs that may regulate galectins were identified using TRANSFAC software and the list obtained was further curated to sort TFs on their confirmed transcript expression in the adult brain. Galectin-TF cluster analysis, gene-ontology annotations and co-expression networks were then extrapolated to predict distinct functional relevance of each galectin in the neuronal processes. Data shows that galectins have highly heterogeneous expression within and across brain sub-structures and are predicted to be the crucial targets of brain enriched TFs. Lgals9 had maximal spatial distribution across mouse brain with inferred predominant roles in neurogenesis while LGALS1 was ubiquitously expressed in human. Limbic region associated with learning, memory and emotions and substantia nigra associated with motor movements showed strikingly high expression of LGALS1 and LGALS8 in human vs. mouse brain. The overall expression profile of galectin-8 was most

Human blood-brain barrier insulin-like growth factor receptor

International Nuclear Information System (INIS)

Duffy, K.R.; Pardridge, W.M.; Rosenfeld, R.G.

1988-01-01

Insulin-like growth factor (IGF)-1 and IGF-2, may be important regulatory molecules in the CNS. Possible origins of IGFs in brain include either de novo synthesis or transport of circulating IGFs from blood into brain via receptor mediated transcytosis mechanisms at the brain capillary endothelial wall, ie, the blood-brain barrier (BBB). In the present studies, isolated human brain capillaries are used as an in vitro model system of the human BBB and the characteristics of IGF-1 or IGF-2 binding to this preparation were assessed. The total binding of IGF-2 at 37 degrees C exceeded 130% per mg protein and was threefold greater than the total binding for IGF-1. However, at 37 degrees C nonsaturable binding equaled total binding, suggesting that endocytosis is rate limiting at physiologic temperatures. Binding studies performed at 4 degrees C slowed endocytosis to a greater extent than membrane binding, and specific binding of either IGF-1 or IGF-2 was detectable. Scatchard plots for either peptide were linear and the molar dissociation constant of IGF-1 and IGF-2 binding was 2.1 +/- 0.4 and 1.1 +/- 0.1 nmol/L, respectively. Superphysiologic concentrations of porcine insulin inhibited the binding of both IGF-1 (ED50 = 2 micrograms/mL) and IGF-2 (ED50 = 0.5 microgram/mL). Affinity cross linking of 125 I-IGF-1, 125 I-IGF-2, and 125 I-insulin to isolated human brain capillaries was performed using disuccinimidylsuberate (DSS). These studies revealed a 141 kd binding site for both IGF-1 and IGF-2, and a 133 kd binding site for insulin

Tailored delivery of analgesic ziconotide across a blood brain barrier model using viral nanocontainers

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Anand, Prachi; O'Neil, Alison; Lin, Emily; Douglas, Trevor; Holford, Mandë

2015-08-01

The blood brain barrier (BBB) is often an insurmountable obstacle for a large number of candidate drugs, including peptides, antibiotics, and chemotherapeutic agents. Devising an adroit delivery method to cross the BBB is essential to unlocking widespread application of peptide therapeutics. Presented here is an engineered nanocontainer for delivering peptidic drugs across the BBB encapsulating the analgesic marine snail peptide ziconotide (Prialt®). We developed a bi-functional viral nanocontainer based on the Salmonella typhimurium bacteriophage P22 capsid, genetically incorporating ziconotide in the interior cavity, and chemically attaching cell penetrating HIV-Tat peptide on the exterior of the capsid. Virus like particles (VLPs) of P22 containing ziconotide were successfully transported in several BBB models of rat and human brain microvascular endothelial cells (BMVEC) using a recyclable noncytotoxic endocytic pathway. This work demonstrates proof in principle for developing a possible alternative to intrathecal injection of ziconotide using a tunable VLP drug delivery nanocontainer to cross the BBB.

Uterine microvascular sensitivity to nanomaterial inhalation: An in vivo assessment

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Stapleton, P.A.; McBride, C.R.; Yi, J.; Nurkiewicz, T.R., E-mail: tnurkiewicz@hsc.wvu.edu

2015-11-01

With the tremendous number and diverse applications of engineered nanomaterials incorporated in daily human activity, exposure can no longer be solely confined to occupational exposures of healthy male models. Cardiovascular and endothelial cell dysfunction have been established using in vitro and in situ preparations, but the translation to intact in vivo models is limited. Intravital microscopy has been used extensively to understand microvascular physiology while maintaining in vivo neurogenic, humoral, and myogenic control. However, a tissue specific model to assess the influences of nanomaterial exposure on female reproductive health has not been fully elucidated. Female Sprague Dawley (SD) rats were exposed to nano-TiO{sub 2} aerosols (171 ± 6 nm, 10.1 ± 0.39 mg/m{sup 3}, 5 h) 24-hours prior to experimentation, leading to a calculated deposition of 42.0 ± 1.65 μg. After verifying estrus status, vital signs were monitored and the right horn of the uterus was exteriorized, gently secured over an optical pedestal, and enclosed in a warmed tissue bath using intravital microscopy techniques. After equilibration, significantly higher leukocyte-endothelium interactions were recorded in the exposed group. Arteriolar responsiveness was assessed using ionophoretically applied agents: muscarinic agonist acetylcholine (0.025 M; ACh; 20, 40, 100, and 200 nA), and nitric oxide donor sodium nitroprusside (0.05 M; SNP; 20, 40, and 100 nA), or adrenergic agonist phenylephrine (0.05 M; PE; 20, 40, and 100 nA) using glass micropipettes. Passive diameter was established by tissue superfusion with 10{sup −4} M adenosine. Similar to male counterparts, female SD rats present systemic microvascular dysfunction; however the ramifications associated with female health and reproduction have yet to be elucidated. - Highlights: • Female reproductive health associated with nanomaterial exposure is understudied. • We examined uterine microvascular alterations 24-hours after nano

Significance of MDR1 and multiple drug resistance in refractory human epileptic brain

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Dini Gabriele

2004-10-01

Full Text Available Abstract Background The multiple drug resistance protein (MDR1/P-glycoprotein is overexpressed in glia and blood-brain barrier (BBB endothelium in drug refractory human epileptic tissue. Since various antiepileptic drugs (AEDs can act as substrates for MDR1, the enhanced expression/function of this protein may increase their active extrusion from the brain, resulting in decreased responsiveness to AEDs. Methods Human drug resistant epileptic brain tissues were collected after surgical resection. Astrocyte cell cultures were established from these tissues, and commercially available normal human astrocytes were used as controls. Uptake of fluorescent doxorubicin and radioactive-labeled Phenytoin was measured in the two cell populations, and the effect of MDR1 blockers was evaluated. Frozen human epileptic brain tissue slices were double immunostained to locate MDR1 in neurons and glia. Other slices were exposed to toxic concentrations of Phenytoin to study cell viability in the presence or absence of a specific MDR1 blocker. Results MDR1 was overexpressed in blood vessels, astrocytes and neurons in human epileptic drug-resistant brain. In addition, MDR1-mediated cellular drug extrusion was increased in human 'epileptic' astrocytes compared to 'normal' ones. Concomitantly, cell viability in the presence of cytotoxic compounds was increased. Conclusions Overexpression of MDR1 in different cell types in drug-resistant epileptic human brain leads to functional alterations, not all of which are linked to drug pharmacokinetics. In particular, the modulation of glioneuronal MDR1 function in epileptic brain in the presence of toxic concentrations of xenobiotics may constitute a novel cytoprotective mechanism.

Human brain lesion-deficit inference remapped.

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Mah, Yee-Haur; Husain, Masud; Rees, Geraint; Nachev, Parashkev

2014-09-01

Our knowledge of the anatomical organization of the human brain in health and disease draws heavily on the study of patients with focal brain lesions. Historically the first method of mapping brain function, it is still potentially the most powerful, establishing the necessity of any putative neural substrate for a given function or deficit. Great inferential power, however, carries a crucial vulnerability: without stronger alternatives any consistent error cannot be easily detected. A hitherto unexamined source of such error is the structure of the high-dimensional distribution of patterns of focal damage, especially in ischaemic injury-the commonest aetiology in lesion-deficit studies-where the anatomy is naturally shaped by the architecture of the vascular tree. This distribution is so complex that analysis of lesion data sets of conventional size cannot illuminate its structure, leaving us in the dark about the presence or absence of such error. To examine this crucial question we assembled the largest known set of focal brain lesions (n = 581), derived from unselected patients with acute ischaemic injury (mean age = 62.3 years, standard deviation = 17.8, male:female ratio = 0.547), visualized with diffusion-weighted magnetic resonance imaging, and processed with validated automated lesion segmentation routines. High-dimensional analysis of this data revealed a hidden bias within the multivariate patterns of damage that will consistently distort lesion-deficit maps, displacing inferred critical regions from their true locations, in a manner opaque to replication. Quantifying the size of this mislocalization demonstrates that past lesion-deficit relationships estimated with conventional inferential methodology are likely to be significantly displaced, by a magnitude dependent on the unknown underlying lesion-deficit relationship itself. Past studies therefore cannot be retrospectively corrected, except by new knowledge that would render them redundant

Assessment of macrovascular endothelial function using pulse wave analysis and its association with microvascular reactivity in healthy subjects.

Science.gov (United States)

Ibrahim, N N I N; Rasool, A H G

2017-08-01

Pulse wave analysis (PWA) and laser Doppler fluximetry (LDF) are non-invasive methods of assessing macrovascular endothelial function and microvascular reactivity respectively. The aim of this study was to assess the correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF. 297 healthy and non-smoking subjects (159 females, mean age (±SD) 23.56 ± 4.54 years) underwent microvascular reactivity assessment using LDF followed by macrovascular endothelial function assessments using PWA. Pearson's correlation showed no correlation between macrovascular endothelial function and microvascular reactivity (r = -0.10, P = 0.12). There was no significant correlation between macrovascular endothelial function assessed by PWA and microvascular reactivity assessed by LDF in healthy subjects. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Measuring and Reconstructing the Brain at the Synaptic Scale: Towards a Biofidelic Human Brain in silico

OpenAIRE

NeuroData; CE, Priebe; Burns, R.; RJ, Vogelstein

2015-01-01

Vogelstein JT, Priebe CE, Burns R, Vogelstein RJ, Lichtman J. Measuring and Reconstructing the Brain at the Synaptic Scale: Towards a Biofidelic Human Brain in silico. DARPA Neural Engineering, Science and Technology Forum, 2010

Revealing the cerebello-ponto-hypothalamic pathway in the human brain.

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Kamali, Arash; Karbasian, Niloofar; Rabiei, Pejman; Cano, Andres; Riascos, Roy F; Tandon, Nitin; Arevalo, Octavio; Ocasio, Laura; Younes, Kyan; Khayat-Khoei, Mahsa; Mirbagheri, Saeedeh; Hasan, Khader M

2018-04-16

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. Copyright © 2018. Published by Elsevier B.V.

Preventing microvascular complications in type 1 diabetes mellitus

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Vijay Viswanathan

2015-01-01

Full Text Available Patients with complications of diabetes such as retinopathy, nephropathy, and cardiovascular complications have increased hospital stay with greater economic burden. Prevention of complications should be started before the onset of type 1 diabetes mellitus (T1DM by working on risk factors and thereafter by intervention upon confirmatory diagnosis which can prevent further damage to β-cells. The actual risk of getting microvascular complications like microalbuminuria and retinopathy progression starts at glycated hemoglobin (HbA1c level of 7%. As per the American Diabetes Association, a new pediatric glycemic control target of HbA1c 20 years as compared to patients <10 years of age. Screening of these complications should be done regularly, and appropriate preventive strategies should be followed. Angiotensin converting enzyme inhibitors and angiotensin II receptor blocker reduce progression from microalbuminuria to macroalbuminuria and increase the regression rate to normoalbuminuria. Diabetic microvascular complications can be controlled with tight glycemic therapy, dyslipidemia management and blood pressure control along with renal function monitoring, lifestyle changes, including smoking cessation and low-protein diet. An integrated and personalized care would reduce the risk of development of microvascular complications in T1DM patients. The child with diabetes who receives limited care is more likely to develop long-term complications at an earlier age. Screening for subclinical complications and early interventions with intensive therapy is the need of the hour.

A digital interactive human brain atlas based on Chinese visible human datasets for anatomy teaching.

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Li, Qiyu; Ran, Xu; Zhang, Shaoxiang; Tan, Liwen; Qiu, Mingguo

2014-01-01

As we know, the human brain is one of the most complicated organs in the human body, which is the key and difficult point in neuroanatomy and sectional anatomy teaching. With the rapid development and extensive application of imaging technology in clinical diagnosis, doctors are facing higher and higher requirement on their anatomy knowledge. Thus, to cultivate medical students to meet the needs of medical development today and to improve their ability to read and understand radiographic images have become urgent challenges for the medical teachers. In this context, we developed a digital interactive human brain atlas based on the Chinese visible human datasets for anatomy teaching (available for free download from http://www.chinesevisiblehuman.com/down/DHBA.rar). The atlas simultaneously provides views in all 3 primary planes of section. The main structures of the human brain have been anatomically labeled in all 3 views. It is potentially useful for anatomy browsing, user self-testing, and automatic student assessment. In a word, it is interactive, 3D, user friendly, and free of charge, which can provide a new, intuitive means for anatomy teaching.

Novel Mechanism of Attenuation of LPS-Induced NF-κB Activation by the Heat Shock Protein 90 Inhibitor, 17-N-allylamino-17-demethoxygeldanamycin, in Human Lung Microvascular Endothelial Cells

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Thangjam, Gagan S.; Dimitropoulou, Chistiana; Joshi, Atul D.; Barabutis, Nektarios; Shaw, Mary C.; Kovalenkov, Yevgeniy; Wallace, Chistopher M.; Fulton, David J.; Patel, Vijay

2014-01-01

Heat shock protein (hsp) 90 inhibition attenuates NF-κB activation and blocks inflammation. However, the precise mechanism of NF-κB regulation by hsp90 in the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-κB activation by LPS in primary human lung microvascular endothelial cells. Transcriptional activation of NF-κB was measured by luciferase reporter assay, gene expression by real-time RT-PCR, DNA binding of transcription factors by chromatin immunoprecipitation assay, protein–protein interaction by coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by partial microccocal DNase digestion. In human lung microvascular endothelial cells, 17-AAG–induced degradation of IKBα was accomplished regardless of the phosphorylation/ubiquitination state of the protein. Hence, 17-AAG did not block LPS-induced NF-κB nuclear translocation and DNA binding activity. Instead, 17-AAG blocked the recruitment of the coactivator, cAMP response element binding protein binding protein, and prevented the assembly of a transcriptionally competent RNA polymerase II complex at the κB elements of the IKBα (an NF-κB–responsive gene) promoter. The effect of LPS on IKBα mRNA expression was associated with rapid deacetylation of histone-H3(Lys9) and a dramatic down-regulation of core histone H3 binding. Even though treatment with an HDAC inhibitor produced the same effect as hsp90 inhibition, the effect of 17-AAG was independent of HDAC. We conclude that hsp90 inhibition attenuates NF-κB transcriptional activation by preventing coactivator recruitment and nucleosome eviction from the target promoter in human lung endothelial cells. PMID:24303801

Smuggling Drugs into the Brain: An Overview of Ligands Targeting Transcytosis for Drug Delivery across the Blood–Brain Barrier

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Julia V. Georgieva

2014-11-01

Full Text Available The blood–brain barrier acts as a physical barrier that prevents free entry of blood-derived substances, including those intended for therapeutic applications. The development of molecular Trojan horses is a promising drug targeting technology that allows for non-invasive delivery of therapeutics into the brain. This concept relies on the application of natural or genetically engineered proteins or small peptides, capable of specifically ferrying a drug-payload that is either directly coupled or encapsulated in an appropriate nanocarrier, across the blood–brain barrier via receptor-mediated transcytosis. Specifically, in this process the nanocarrier–drug system (“Trojan horse complex” is transported transcellularly across the brain endothelium, from the blood to the brain interface, essentially trailed by a native receptor. Naturally, only certain properties would favor a receptor to serve as a transporter for nanocarriers, coated with appropriate ligands. Here we briefly discuss brain microvascular endothelial receptors that have been explored until now, highlighting molecular features that govern the efficiency of nanocarrier-mediated drug delivery into the brain.

Impaired coronary microvascular function in diabetics

International Nuclear Information System (INIS)

Tsujimoto, Go

2000-01-01

Global and regional myocardial uptake was determined with technetium-99m tetrofosmin and a 4 hour exercise (370 MBq iv) and rest (740 MBq iv) protocol, in 24 patients with non-insulin dependent diabetes mellitus and in 22 control subjects. The purpose of this study was to evaluate impaired coronary microvascular function in diabetics by measurement of % uptake increase in myocardial counts. The parameter of % uptake increase (ΔMTU) was calculated as the ratio of exercise counts to rest myocardial counts with correction of myocardial uptake for dose administered and physical decay between the exercise study and the rest study. Global ΔMTU was significantly lower in the diabetics than in control subjects (14.4±5.4% vs. 21.7±8.5%, p<0.01). Regional ΔMTU in each of 4 left ventricular regions (anterior, septal, inferior, posterolateral) was significantly lower in the diabetic group than in the control group (p<0.01) respectively, but there were no significant differences between ΔMTU in the 4 left ventricular regions in the same group. ΔMTU was useful as a non-invasive means of evaluating impaired coronary microvascular function in diabetics. (author)

Brain Imaging of Human Sexual Response : Recent Developments and Future Directions

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Ruesink, Gerben B; Georgiadis, Janniko R

2017-01-01

Purpose of Review: The purpose of this study is to provide a comprehensive summary of the latest developments in the experimental brain study of human sexuality, focusing on brain connectivity during the sexual response. Recent Findings: Stable patterns of brain activation have been established for

Identification of Multipotent Stem Cells in Human Brain Tissue Following Stroke.

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Tatebayashi, Kotaro; Tanaka, Yasue; Nakano-Doi, Akiko; Sakuma, Rika; Kamachi, Saeko; Shirakawa, Manabu; Uchida, Kazutaka; Kageyama, Hiroto; Takagi, Toshinori; Yoshimura, Shinichi; Matsuyama, Tomohiro; Nakagomi, Takayuki

2017-06-01

Perivascular regions of the brain harbor multipotent stem cells. We previously demonstrated that brain pericytes near blood vessels also develop multipotency following experimental ischemia in mice and these ischemia-induced multipotent stem cells (iSCs) can contribute to neurogenesis. However, it is essential to understand the traits of iSCs in the poststroke human brain for possible applications in stem cell-based therapies for stroke patients. In this study, we report for the first time that iSCs can be isolated from the poststroke human brain. Putative iSCs were derived from poststroke brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that these iSCs were localized near blood vessels within poststroke areas containing apoptotic/necrotic neurons and expressed both the stem cell marker nestin and several pericytic markers. Isolated iSCs expressed these same markers and demonstrated high proliferative potential without loss of stemness. Furthermore, isolated iSCs expressed other stem cell markers, such as Sox2, c-myc, and Klf4, and differentiated into multiple cells in vitro, including neurons. These results show that iSCs, which are likely brain pericyte derivatives, are present within the poststroke human brain. This study suggests that iSCs can contribute to neural repair in patients with stroke.

Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer's Disease Brain

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Sarah L. DeVos

2018-04-01

Full Text Available Alzheimer's disease (AD is defined by the presence of intraneuronal neurofibrillary tangles (NFTs composed of hyperphosphorylated tau aggregates as well as extracellular amyloid-beta plaques. The presence and spread of tau pathology through the brain is classified by Braak stages and thought to correlate with the progression of AD. Several in vitro and in vivo studies have examined the ability of tau pathology to move from one neuron to the next, suggesting a “prion-like” spread of tau aggregates may be an underlying cause of Braak tau staging in AD. Using the HEK293 TauRD-P301S-CFP/YFP expressing biosensor cells as a highly sensitive and specific tool to identify the presence of seed competent aggregated tau in brain lysate—i.e., tau aggregates that are capable of recruiting and misfolding monomeric tau—, we detected substantial tau seeding levels in the entorhinal cortex from human cases with only very rare NFTs, suggesting that soluble tau aggregates can exist prior to the development of overt tau pathology. We next looked at tau seeding levels in human brains of varying Braak stages along six regions of the Braak Tau Pathway. Tau seeding levels were detected not only in the brain regions impacted by pathology, but also in the subsequent non-pathology containing region along the Braak pathway. These data imply that pathogenic tau aggregates precede overt tau pathology in a manner that is consistent with transneuronal spread of tau aggregates. We then detected tau seeding in frontal white matter tracts and the optic nerve, two brain regions comprised of axons that contain little to no neuronal cell bodies, implying that tau aggregates can indeed traverse along axons. Finally, we isolated cytosolic and synaptosome fractions along the Braak Tau Pathway from brains of varying Braak stages. Phosphorylated and seed competent tau was significantly enriched in the synaptic fraction of brain regions that did not have extensive cellular tau

Regional distribution of serotonin transporter protein in postmortem human brain

International Nuclear Information System (INIS)

Kish, Stephen J.; Furukawa, Yoshiaki; Chang Lijan; Tong Junchao; Ginovart, Nathalie; Wilson, Alan; Houle, Sylvain; Meyer, Jeffrey H.

2005-01-01

Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met

Regional distribution of serotonin transporter protein in postmortem human brain

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Kish, Stephen J. [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)]. E-mail: Stephen_Kish@CAMH.net; Furukawa, Yoshiaki [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Chang Lijan [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Tong Junchao [Human Neurochemical Pathology Laboratory, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Ginovart, Nathalie [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Wilson, Alan [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Meyer, Jeffrey H. [PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

2005-02-01

Introduction: The primary approach in assessing the status of brain serotonin neurons in human conditions such as major depression and exposure to the illicit drug ecstasy has been the use of neuroimaging procedures involving radiotracers that bind to the serotonin transporter (SERT). However, there has been no consistency in the selection of a 'SERT-free' reference region for the estimation of free and nonspecific binding, as occipital cortex, cerebellum and white matter have all been employed. Objective and Methods: To identify areas of human brain that might have very low SERT levels, we measured, by a semiquantitative Western blotting procedure, SERT protein immunoreactivity throughout the postmortem brain of seven normal adult subjects. Results: Serotonin transporter could be quantitated in all examined brain areas. However, the SERT concentration in cerebellar cortex and white matter were only at trace values, being approximately 20% of average cerebral cortex and 5% of average striatum values. Conclusion: Although none of the examined brain areas are completely free of SERT, human cerebellar cortex has low SERT binding as compared to other examined brain regions, with the exception of white matter. Since the cerebellar cortical SERT binding is not zero, this region will not be a suitable reference region for SERT radioligands with very low free and nonspecific binding. For SERT radioligands with reasonably high free and nonspecific binding, the cerebellar cortex should be a useful reference region, provided other necessary radioligand assumptions are met.

Microvascular versus macrovascular cerebral vasomotor reactivity in patients with severe internal carotid artery stenosis or occlusion.

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Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Martí-Fàbregas, Joan; Durduran, Turgut

2014-02-01

In patients with severe internal carotid artery steno-occlusive lesions (ISOL), impaired cerebrovascular reactivity (CVR) is predictive of future ischemic stroke (IS) or transient ischemic attack (TIA). Therefore, the evaluation of CVR in ISOL patients may be a means to evaluate the risk for IS/TIA and decide on an intervention. Our aim was (1) to explore the feasibility of concurrent near-infrared spectroscopy (NIRS-DOS), diffuse correlation spectroscopy, and transcranial Doppler for CVR assessment in ISOL patients, and (2) to compare macrovascular and microvascular CVR in ISOL patients and explore its potential for IS/TIA risk stratification. Twenty-seven ISOL patients were recruited. The changes in continuous microvascular and macrovascular hemodynamics upon acetazolamide injection were used to determine CVR. Oxyhemoglobin (HbO2, by near-infrared spectroscopy), microvascular cerebral blood flow (CBF, by diffuse correlation spectroscopy) and CBF velocity (by transcranial Doppler) showed significant increases upon acetazolamide injection in all subjects (P < .03). Only macrovascular CVR (P = .024) and none of the microvascular measures were significantly dependent on the presence of ISOL. In addition, while CBF was significantly correlated with HbO2, neither of these microvascular measures correlated with macrovascular CBF velocity. We demonstrated the simultaneous, continuous, and noninvasive evaluation of CVR at both the microvasculature and macrovasculature. We found that macrovascular CVR response depends on the presence of ISOL, whereas the microvascular CVR did not significantly depend on the ISOL presence, possibly due to the role of collaterals other than those of the circle of Willis. The concurrent microvascular and macrovascular CVR measurement in the ISOL patients might improve future IS/TIA risk assessment. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction

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Qiu, Gui-Zhen [Department of Health, Linyi People' s Hospital, Shandong University, Shandong (China); Tian, Wei [Department of Nursing, Linyi Oncosurgical Hospital, Shandong (China); Fu, Hai-Tao [Department of Ophthalmology, Linyi People' s Hospital, Shandong University, Shandong (China); Li, Chao-Peng, E-mail: lcpcn@163.com [Eye Institute of Xuzhou, Jiangsu (China); Liu, Ban, E-mail: liuban@126.com [Department of Cardiology, Shanghai Tenth People' s Hospital, Tongji University School of Medicine, Shanghai (China)

2016-02-26

Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. - Highlights: • LncRNA-MEG3 level is down-regulated upon diabetic stress. • MEG3 knockdown aggravates retinal vascular dysfunction in vivo. • MEG3 regulates retinal endothelial cell function in vitro. • MEG3 regulates endothelial cell function through PI3k/Akt signaling.

Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction

International Nuclear Information System (INIS)

Qiu, Gui-Zhen; Tian, Wei; Fu, Hai-Tao; Li, Chao-Peng; Liu, Ban

2016-01-01

Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. - Highlights: • LncRNA-MEG3 level is down-regulated upon diabetic stress. • MEG3 knockdown aggravates retinal vascular dysfunction in vivo. • MEG3 regulates retinal endothelial cell function in vitro. • MEG3 regulates endothelial cell function through PI3k/Akt signaling.

Mary Jane Hogue (1883-1962): A pioneer in human brain tissue culture.

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Zottoli, Steven J; Seyfarth, Ernst-August

2018-05-16

The ability to maintain human brain explants in tissue culture was a critical step in the use of these cells for the study of central nervous system disorders. Ross G. Harrison (1870-1959) was the first to successfully maintain frog medullary tissue in culture in 1907, but it took another 38 years before successful culture of human brain tissue was accomplished. One of the pioneers in this achievement was Mary Jane Hogue (1883-1962). Hogue was born into a Quaker family in 1883 in West Chester, Pennsylvania, and received her undergraduate degree from Goucher College in Baltimore, Maryland. Research with the developmental biologist Theodor Boveri (1862-1915) in Würzburg, Germany, resulted in her Ph.D. (1909). Hogue transitioned from studying protozoa to the culture of human brain tissue in the 1940s and 1950s, when she was one of the first to culture cells from human fetal, infant, and adult brain explants. We review Hogue's pioneering contributions to the study of human brain cells in culture, her putative identification of progenitor neuroblast and/or glioblast cells, and her use of the cultures to study the cytopathogenic effects of poliovirus. We also put Hogue's work in perspective by discussing how other women pioneers in tissue culture influenced Hogue and her research.

Dysregulation of coronary microvascular reactivity in asymptomatic patients with type 2 diabetes mellitus

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Momose, Mitsuru; Neverve, Jodi; Nekolla, Stephan G.; Schwaiger, Markus; Bengel, Frank M. [Nuklearmedizinische Klinik und Poliklinik der Technischen Universitaet Muenchen, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 Munich (Germany); Abletshauser, Claudia [Department of Medicine, Novartis Pharma GmbH, Nuernberg (Germany); Schnell, Oliver; Standl, Eberhard [Institut fuer Diabetesforschung, Munich (Germany)

2002-12-01

In diabetic patients, a number of studies have suggested an impairment of vascular reactivity in response to vasodilatory stimuli. The pattern of dysregulation at the coronary microcirculatory level, however, has not been clearly defined. Thus, it was the aim of this study to characterise coronary microvascular function non-invasively in a homogeneous group of asymptomatic type 2 diabetic patients. In 46 patients with type 2 diabetes, myocardial blood flow (MBF) was quantified at baseline, in response to cold pressor test (CPT) and during adenosine-mediated vasodilation using positron emission tomography and nitrogen-13 ammonia. None of the patients had been treated with insulin, and none had symptoms of cardiac disease. Decreased MBF during CPT, indicating microvascular dysregulation, was observed in 16 patients (CPT-), while 30 patients demonstrated increased MBF during CPT (CPT+). Response to CPT was mildly, but significantly correlated with response to adenosine (r=0.44, P=0.0035). There was no difference in HbA1c, serum lipid levels or serum endothelial markers between the groups. Microvascular dysregulation in the CPT- group was associated with elevated baseline MBF (P<0.0001), reduced baseline vascular resistance (P=0.0026) and an abnormal increase in resistance during CPT (P=0.0002). In conclusion, coronary microvascular dysregulation is present in approximately one-third of asymptomatic, non-insulin-treated type 2 diabetic patients. Elevated baseline blood flow and reduced microvascular resistance at rest are characteristics of this dysregulation. These data suggest a state of activation of endothelial-dependent vasodilation at baseline which appears to limit the flow response to stress conditions. (orig.)

Design, manufacture and in-vitro evaluation of a new microvascular anastomotic device.

Science.gov (United States)

Huang, Shao-Fu; Wang, Tien-Hsiang; Wang, Hsuan-Wen; Huang, Shu-Wei; Lin, Chun-Li; Kuo, Hsien-Nan; Yu, Tsung-Chih

2013-01-01

Many microvascular anastomoses have been proposed for use with physical assisted methods, such as cuff, ring-pin, stapler, clip to the anastomose blood vessel. The ring-pin type anastomotic device (e.g., 3M Microvascular Anastomotic System) is the most commonly used worldwide because the anastomotic procedure can be conducted more rapidly and with fewer traumas than using sutures. However, problems including vessel leakage, ring slippage, high cost and high surgical skill demand need to be resolved. The aim of this study is to design and manufacture a new anastomotic device for microvascular anastomosis surgery and validate the device functions with in-vitro testing. The new device includes one pair of pinned rings and a set of semi-automatic flap apparatus designed and made using computer-aided design / computer-aided manufacture program. A pair of pinned rings was used to impale vessel walls and establish fluid communication with rings joined. The semi-automatic flap apparatus was used to assist the surgeon to invert the vessel walls and impale onto each ring pin, then turning the apparatus knob to bring the rings together. The device was revised until it became acceptable for clinical requires. An in-vitro test was performed using a custom-made seepage micro-fluid system to detect the leakage of the anastomotic rings. The variation between input and output flow for microvascular anastomoses was evaluated. The new microvascular anastomotic device was convenient and easy to use. It requires less time than sutures to invert and impale vessel walls onto the pinned rings using the semi-automatic flap apparatus. The in-vitro test data showed that there were no tears from the joined rings seam during the procedures. The new anastomotic devices are effective even with some limitations still remaining. This device can be helpful to simplify the anastomosis procedure and reduce the surgery time.

Dual energy spectral CT imaging for the evaluation of small hepatocellular carcinoma microvascular invasion.

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Yang, Chuang-Bo; Zhang, Shuang; Jia, Yong-Jun; Yu, Yong; Duan, Hai-Feng; Zhang, Xi-Rong; Ma, Guang-Ming; Ren, Chenglong; Yu, Nan

2017-10-01

To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma. This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RIC AP-VP : [RIC AP-VP =(IC AP -IC VP )/IC AP ]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison. 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RIC AP-VP between Group A (2.48±0.70mg/ml, 0.23±0.05, 3.39±1.01 and 0.28±0.16) and Group B (1.65±0.47mg/ml, 0.15±0.05, 2.22±0.64 and 0.03±0.24) (all phepatocellular carcinoma with and without microvascular invasion. Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhaled nitric oxide pretreatment but not posttreatment attenuates ischemia-reperfusion-induced pulmonary microvascular leak.

Science.gov (United States)

Chetham, P M; Sefton, W D; Bridges, J P; Stevens, T; McMurtry, I F

1997-04-01

Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown. Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 microM) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 microM), and Kfc was estimated at baseline and after 30 min of reperfusion. (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective. Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.

Brain mechanisms underlying human communication

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Matthijs L Noordzij

2009-07-01

Full Text Available Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the “mirror neurons system”. However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender and recognizing the communicative intention of the same actions (by a receiver relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus. The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

Brain mechanisms underlying human communication.

Science.gov (United States)

Noordzij, Matthijs L; Newman-Norlund, Sarah E; de Ruiter, Jan Peter; Hagoort, Peter; Levinson, Stephen C; Toni, Ivan

2009-01-01

Human communication has been described as involving the coding-decoding of a conventional symbol system, which could be supported by parts of the human motor system (i.e. the "mirror neurons system"). However, this view does not explain how these conventions could develop in the first place. Here we target the neglected but crucial issue of how people organize their non-verbal behavior to communicate a given intention without pre-established conventions. We have measured behavioral and brain responses in pairs of subjects during communicative exchanges occurring in a real, interactive, on-line social context. In two fMRI studies, we found robust evidence that planning new communicative actions (by a sender) and recognizing the communicative intention of the same actions (by a receiver) relied on spatially overlapping portions of their brains (the right posterior superior temporal sulcus). The response of this region was lateralized to the right hemisphere, modulated by the ambiguity in meaning of the communicative acts, but not by their sensorimotor complexity. These results indicate that the sender of a communicative signal uses his own intention recognition system to make a prediction of the intention recognition performed by the receiver. This finding supports the notion that our communicative abilities are distinct from both sensorimotor processes and language abilities.

Activation analysis study on subcellular distribution of trace elements in human brain tumor

International Nuclear Information System (INIS)

Zheng Jian; Zhuan Guisun; Wang Yongji; Dong Mo; Zhang Fulin

1992-01-01

The concentrations of up to 11 elements in subcellular fractions of human brain (normal and malignant tumor) have been determined by a combination of gradient centrifugation and INAA methods. Samples of human brain were homogenized in a glass homogenizer tube, the homogenate was separated into nuclei, mitochondrial, myelin, synaptosome fractions, and these fractions were then analyzed using the INAA method. The discussions of elemental subcelleular distributions in human brain malignant tumor are presented in this paper. (author) 11 refs.; 2 figs.; 4 tabs

ALFY-Controlled DVL3 Autophagy Regulates Wnt Signaling, Determining Human Brain Size.

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Rotem Kadir

2016-03-01

Full Text Available Primary microcephaly is a congenital neurodevelopmental disorder of reduced head circumference and brain volume, with fewer neurons in the cortex of the developing brain due to premature transition between symmetrical and asymmetrical cellular division of the neuronal stem cell layer during neurogenesis. We now show through linkage analysis and whole exome sequencing, that a dominant mutation in ALFY, encoding an autophagy scaffold protein, causes human primary microcephaly. We demonstrate the dominant effect of the mutation in drosophila: transgenic flies harboring the human mutant allele display small brain volume, recapitulating the disease phenotype. Moreover, eye-specific expression of human mutant ALFY causes rough eye phenotype. In molecular terms, we demonstrate that normally ALFY attenuates the canonical Wnt signaling pathway via autophagy-dependent removal specifically of aggregates of DVL3 and not of Dvl1 or Dvl2. Thus, autophagic attenuation of Wnt signaling through removal of Dvl3 aggregates by ALFY acts in determining human brain size.

Human brain functional MRI and DTI visualization with virtual reality.

Science.gov (United States)

Chen, Bin; Moreland, John; Zhang, Jingyu

2011-12-01

Magnetic resonance diffusion tensor imaging (DTI) and functional MRI (fMRI) are two active research areas in neuroimaging. DTI is sensitive to the anisotropic diffusion of water exerted by its macromolecular environment and has been shown useful in characterizing structures of ordered tissues such as the brain white matter, myocardium, and cartilage. The diffusion tensor provides two new types of information of water diffusion: the magnitude and the spatial orientation of water diffusivity inside the tissue. This information has been used for white matter fiber tracking to review physical neuronal pathways inside the brain. Functional MRI measures brain activations using the hemodynamic response. The statistically derived activation map corresponds to human brain functional activities caused by neuronal activities. The combination of these two methods provides a new way to understand human brain from the anatomical neuronal fiber connectivity to functional activities between different brain regions. In this study, virtual reality (VR) based MR DTI and fMRI visualization with high resolution anatomical image segmentation and registration, ROI definition and neuronal white matter fiber tractography visualization and fMRI activation map integration is proposed. Rationale and methods for producing and distributing stereoscopic videos are also discussed.

Differing levels of excision repair in human fetal dermis and brain cells

International Nuclear Information System (INIS)

Gibson, R.E.; D'Ambrosio, S.M.; Ohio State Univ., Columbus

1982-01-01

The levels of DNA excision repair, as measured by unscheduled DNA synthesis (UDS) and the UV-endonuclease sensitive site assay, were compared in cells derived from human fetal brain and dermal tissues. The level of UDS induced following ultraviolet (UV) irradiation was found to be lower (approx. 60%) in the fetal brain cells than in fetal dermal cells. It was determined, using the UV-endonuclease sensitive site assay to confirm the UDS observation, that 50% of the dimers induced by UV in fetal dermal cells were repaired in 8 h. while only 15% were removed in the fetal brain cells during the same period of time. Even after 24 h. only 44% of the dimers induced by UV in the fetal brain cells were repaired, while 65% were removed in the dermal cells. These data suggest that cultured human fetal brain cells exhibit lower levels of excision repair compared to cultured human fetal dermal cells. (author)

Tolerances of the human brain to concussion.

Science.gov (United States)

1971-03-01

The report reviews the pertinent literature and adds additional evidence indicating that the human brain may be able to tolerate head impact forces in the range of 300 to 400 g's without evidence of concussion or other detectable neurologic sequelae,...

Recent Developments in Understanding Brain Aging: Implications for Alzheimer’s Disease and Vascular Cognitive Impairment

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Deak, Ferenc; Freeman, Willard M.; Ungvari, Zoltan; Csiszar, Anna

2016-01-01

As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer’s disease. PMID:26590911

Xanthine oxidase activity regulates human embryonic brain cells growth

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Kevorkian G. A.

2011-10-01

Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

The Complex Functioning of the Human Brain: The Two Hemispheres

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Iulia Cristina Timofti

2010-04-01

Full Text Available The present study reveals just a glimpse of the possible functions and reactions that the human brain can have. I considered as good examples different situations characteristic both of a normal person and a split-brain one. These situations prove that the brain, although divided in two, works as a unit, as an amazing computer that has data processing as a main goal.

Human brain organoids on a chip reveal the physics of folding

Science.gov (United States)

Karzbrun, Eyal; Kshirsagar, Aditya; Cohen, Sidney R.; Hanna, Jacob H.; Reiner, Orly

2018-05-01

Human brain wrinkling has been implicated in neurodevelopmental disorders and yet its origins remain unknown. Polymer gel models suggest that wrinkling emerges spontaneously due to compression forces arising during differential swelling, but these ideas have not been tested in a living system. Here, we report the appearance of surface wrinkles during the in vitro development and self-organization of human brain organoids in a microfabricated compartment that supports in situ imaging over a timescale of weeks. We observe the emergence of convolutions at a critical cell density and maximal nuclear strain, which are indicative of a mechanical instability. We identify two opposing forces contributing to differential growth: cytoskeletal contraction at the organoid core and cell-cycle-dependent nuclear expansion at the organoid perimeter. The wrinkling wavelength exhibits linear scaling with tissue thickness, consistent with balanced bending and stretching energies. Lissencephalic (smooth brain) organoids display reduced convolutions, modified scaling and a reduced elastic modulus. Although the mechanism here does not include the neuronal migration seen in vivo, it models the physics of the folding brain remarkably well. Our on-chip approach offers a means for studying the emergent properties of organoid development, with implications for the embryonic human brain.

Comparison between invasive and noninvasive techniques of evaluation of microvascular structural alterations.

Science.gov (United States)

De Ciuceis, Carolina; Agabiti Rosei, Claudia; Caletti, Stefano; Trapletti, Valentina; Coschignano, Maria A; Tiberio, Guido A M; Duse, Sarah; Docchio, Franco; Pasinetti, Simone; Zambonardi, Federica; Semeraro, Francesco; Porteri, Enzo; Solaini, Leonardo; Sansoni, Giovanna; Pileri, Paola; Rossini, Claudia; Mittempergher, Francesco; Portolani, Nazario; Ministrini, Silvia; Agabiti-Rosei, Enrico; Rizzoni, Damiano

2018-05-01

The evaluation of the morphological characteristics of small resistance arteries in humans is challenging. The gold standard method is generally considered to be the measurement by wire or pressure micromyography of the media-to-lumen ratio of subcutaneous small vessels obtained by local biopsies. However, noninvasive techniques for the evaluation of retinal arterioles were recently proposed; in particular, two approaches, scanning laser Doppler flowmetry (SLDF) and adaptive optics, seem to provide useful information; both of them provide an estimation of the wall-to-lumen ratio (WLR) of retinal arterioles. Moreover, a noninvasive measurement of basal and total capillary density may be obtained by videomicroscopy/capillaroscopy. No direct comparison of these three noninvasive techniques in the same population was previously performed; in particular, adaptive optics was never validated against micromyography. In the current study, we enrolled 41 controls and patients: 12 normotensive lean controls, 12 essential hypertensive lean patients, nine normotensive obese patients and eight hypertensive obese patients undergoing elective surgery. All patients underwent a biopsy of subcutaneous fat during surgery. Subcutaneous small resistance artery structure was assessed by wire micromyography and the media-to-lumen ratio was calculated. WLR of retinal arterioles was obtained by SLDF and adaptive optics. Functional (basal) and structural (total) microvascular density was evaluated by capillaroscopy before and after venous congestion. Our data suggest that adaptive optics has a substantial advantage over SLDF in terms of evaluation of microvascular morphology, as WLR measured with adaptive optics is more closely correlated with the M/L of subcutaneous small arteries (r = 0.84, P < 0.001 vs. r = 0.52, P < 0.05, slopes of the relations: P < 0.01 adaptive optics vs. SLDF). In addition, the reproducibility of the evaluation of the WLR with adaptive optics is

Treatment of Angina and Microvascular Coronary Dysfunction

Science.gov (United States)

Samim, Arang; Nugent, Lynn; Mehta, Puja K.; Shufelt, Chrisandra; Merz, C. Noel Bairey

2014-01-01

Opinion statement Microvascular coronary dysfunction (MCD) is an increasingly recognized cause of cardiac ischemia and angina, more commonly diagnosed in women. Patients with MCD present with the triad of persistent chest pain, ischemic changes on stress testing, and no obstructive coronary artery disease (CAD) on cardiac catheterization. Data from National Heart, Lung and Blood Institute (NHLBI)-sponsored Women’s Ischemia Syndrome Evaluation (WISE) study has shown that the diagnosis of MCD is not benign, with a 2.5% annual risk of adverse cardiac events including myocardial infarction, stroke, congestive heart failure, or death. The gold standard diagnostic test for MCD is an invasive coronary reactivity test (CRT), which uses acetylcholine, adenosine, and nitroglycerin to test the endothelial dependent and independent, microvascular and macrovascular coronary function. The CRT allows for diagnostic and treatment options as well as further risk stratifying patients for future cardiovascular events. Treatment of angina and MCD should be aimed at ischemia disease management to reduce risk of adverse cardiac events, ameliorating symptoms to improve quality of life, and to decrease the morbidity from unnecessary and repeated cardiac catheterization in patients with open coronary arteries. A comprehensive treatment approach aimed at risk factor managment, including lifestyle counseling regarding smoking cessation, nutrition and physical activity should be initiated. Current pharmacotherapy for MCD can include the treatment of microvascular endothelial dysfunction (statins, angiotensin-converting enzyme inhibitor, low dose aspirin), as well as treatment for angina and myocardial ischemia (beta blockers, calcium channel blockers, nitrates, ranolazine). Additional symptom management techniques can include tri-cyclic medication, enhanced external counterpulsation, autogenic training, and spinal cord stimulation. While our current therapies are effective in the treatment

Transcriptional profiling of human glioblastoma vessels indicates a key role of VEGF-A and TGF beta 2 in vascular abnormalization

NARCIS (Netherlands)

Dieterich, Lothar C.; Mellberg, Sofie; Langenkamp, Elise; Zhang, Lei; Zieba, Agata; Salomaki, Henriikka; Teichert, Martin; Huang, Hua; Edqvist, Per-Henrik; Kraus, Theo; Augustin, Hellmut G.; Olofsson, Tommie; Larsson, Erik; Soderberg, Ola; Molema, Grietje; Ponten, Fredrik; Georgii-Hemming, Patrik; Alafuzoff, Irina; Dimberg, Anna

2012-01-01

Glioblastoma are aggressive astrocytic brain tumours characterized by microvascular proliferation and an abnormal vasculature, giving rise to brain oedema and increased patient morbidity. Here, we have characterized the transcriptome of tumour-associated blood vessels and describe a gene signature

Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions.

Science.gov (United States)

Chapouly, Candice; Tadesse Argaw, Azeb; Horng, Sam; Castro, Kamilah; Zhang, Jingya; Asp, Linnea; Loo, Hannah; Laitman, Benjamin M; Mariani, John N; Straus Farber, Rebecca; Zaslavsky, Elena; Nudelman, German; Raine, Cedric S; John, Gareth R

2015-06-01

In inflammatory central nervous system conditions such as multiple sclerosis, breakdown of the blood-brain barrier is a key event in lesion pathogenesis, predisposing to oedema, excitotoxicity, and ingress of plasma proteins and inflammatory cells. Recently, we showed that reactive astrocytes drive blood-brain barrier opening, via production of vascular endothelial growth factor A (VEGFA). Here, we now identify thymidine phosphorylase (TYMP; previously known as endothelial cell growth factor 1, ECGF1) as a second key astrocyte-derived permeability factor, which interacts with VEGFA to induce blood-brain barrier disruption. The two are co-induced NFκB1-dependently in human astrocytes by the cytokine interleukin 1 beta (IL1B), and inactivation of Vegfa in vivo potentiates TYMP induction. In human central nervous system microvascular endothelial cells, VEGFA and the TYMP product 2-deoxy-d-ribose cooperatively repress tight junction proteins, driving permeability. Notably, this response represents part of a wider pattern of endothelial plasticity: 2-deoxy-d-ribose and VEGFA produce transcriptional programs encompassing angiogenic and permeability genes, and together regulate a third unique cohort. Functionally, each promotes proliferation and viability, and they cooperatively drive motility and angiogenesis. Importantly, introduction of either into mouse cortex promotes blood-brain barrier breakdown, and together they induce severe barrier disruption. In the multiple sclerosis model experimental autoimmune encephalitis, TYMP and VEGFA co-localize to reactive astrocytes, and correlate with blood-brain barrier permeability. Critically, blockade of either reduces neurologic deficit, blood-brain barrier disruption and pathology, and inhibiting both in combination enhances tissue preservation. Suggesting importance in human disease, TYMP and VEGFA both localize to reactive astrocytes in multiple sclerosis lesion samples. Collectively, these data identify TYMP as an

Angiogenesis in gliomas.

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Elzbieta Czykier

2008-02-01

Full Text Available Brain gliomas are characterized by invasive growth and neovascularisation potential. Angiogenesis plays a major role in the progression of gliomas and its determination has a great prognostic value. The aim of the study was to assess the vascularisation of chosen brain gliomas and to estimate how it is correlated with tumour histological type, malignancy grade, location and size, and with age and sex of patients. Tumour vascularisation analysis was based on the determination of microvascular proliferation (MVP and microvessel density (MVD. Microvascular proliferation was measured with immunohistochemical methods using mouse monoclonal antibodies to detect cell proliferation antigens. The following antibodies were used Ki-67 and PCNA (DAKO. Identification of vessels was performed by CD31 antibody and anti-human von Willebrand factor (DAKO. The highest microvascular proliferation and microvascular density were observed in multiform glioblastomas and the lowest in oligodendrogliomas. Significant correlation was observed between the vascularisation and malignancy grade.

Accelerated differentiation of human induced pluripotent stem cells to blood-brain barrier endothelial cells.

Science.gov (United States)

Hollmann, Emma K; Bailey, Amanda K; Potharazu, Archit V; Neely, M Diana; Bowman, Aaron B; Lippmann, Ethan S

2017-04-13

Due to their ability to limitlessly proliferate and specialize into almost any cell type, human induced pluripotent stem cells (iPSCs) offer an unprecedented opportunity to generate human brain microvascular endothelial cells (BMECs), which compose the blood-brain barrier (BBB), for research purposes. Unfortunately, the time, expense, and expertise required to differentiate iPSCs to purified BMECs precludes their widespread use. Here, we report the use of a defined medium that accelerates the differentiation of iPSCs to BMECs while achieving comparable performance to BMECs produced by established methods. Induced pluripotent stem cells were seeded at defined densities and differentiated to BMECs using defined medium termed E6. Resultant purified BMEC phenotypes were assessed through trans-endothelial electrical resistance (TEER), fluorescein permeability, and P-glycoprotein and MRP family efflux transporter activity. Expression of endothelial markers and their signature tight junction proteins were confirmed using immunocytochemistry. The influence of co-culture with astrocytes and pericytes on purified BMECs was assessed via TEER measurements. The robustness of the differentiation method was confirmed across independent iPSC lines. The use of E6 medium, coupled with updated culture methods, reduced the differentiation time of iPSCs to BMECs from thirteen to 8 days. E6-derived BMECs expressed GLUT-1, claudin-5, occludin, PECAM-1, and VE-cadherin and consistently achieved TEER values exceeding 2500 Ω × cm 2 across multiple iPSC lines, with a maximum TEER value of 4678 ± 49 Ω × cm 2 and fluorescein permeability below 1.95 × 10 -7 cm/s. E6-derived BMECs maintained TEER above 1000 Ω × cm 2 for a minimum of 8 days and showed no statistical difference in efflux transporter activity compared to BMECs differentiated by conventional means. The method was also found to support long-term stability of BMECs harboring biallelic PARK2 mutations associated

Reflectance diffuse optical tomography. Its application to human brain mapping

International Nuclear Information System (INIS)

Ueda, Yukio; Yamanaka, Takeshi; Yamashita, Daisuke; Suzuki, Toshihiko; Ohmae, Etsuko; Oda, Motoki; Yamashita, Yutaka

2005-01-01

We report the successful application of reflectance diffuse optical tomography (DOT) using near-infrared light with the new reconstruction algorithm that we developed to the observation of regional hemodynamic changes in the brain under specific mental tasks. Our results reveal the heterogeneous distribution of oxyhemoglobin and deoxyhemoglobin in the brain, showing complementary images of oxyhemoglobin and deoxyhemoglobin changes in certain regions. We conclude that our reflectance DOT has practical potential for human brain mapping, as well as in the diagnostic imaging of brain diseases. (author)

Hemispheric Asymmetry of Human Brain Anatomical Network Revealed by Diffusion Tensor Tractography

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Ni Shu

2015-01-01

Full Text Available The topological architecture of the cerebral anatomical network reflects the structural organization of the human brain. Recently, topological measures based on graph theory have provided new approaches for quantifying large-scale anatomical networks. However, few studies have investigated the hemispheric asymmetries of the human brain from the perspective of the network model, and little is known about the asymmetries of the connection patterns of brain regions, which may reflect the functional integration and interaction between different regions. Here, we utilized diffusion tensor imaging to construct binary anatomical networks for 72 right-handed healthy adult subjects. We established the existence of structural connections between any pair of the 90 cortical and subcortical regions using deterministic tractography. To investigate the hemispheric asymmetries of the brain, statistical analyses were performed to reveal the brain regions with significant differences between bilateral topological properties, such as degree of connectivity, characteristic path length, and betweenness centrality. Furthermore, local structural connections were also investigated to examine the local asymmetries of some specific white matter tracts. From the perspective of both the global and local connection patterns, we identified the brain regions with hemispheric asymmetries. Combined with the previous studies, we suggested that the topological asymmetries in the anatomical network may reflect the functional lateralization of the human brain.

Cerebral Microcirculation and Oxygen Tension in the Human Secondary Cortex

Science.gov (United States)

Linninger, A. A.; Gould, I. G.; Marinnan, T.; Hsu, C.-Y.; Chojecki, M.; Alaraj, A.

2013-01-01

The three-dimensional spatial arrangement of the cortical microcirculatory system is critical for understanding oxygen exchange between blood vessels and brain cells. A three-dimensional computer model of a 3 × 3 × 3 mm3 subsection of the human secondary cortex was constructed to quantify oxygen advection in the microcirculation, tissue oxygen perfusion, and consumption in the human cortex. This computer model accounts for all arterial, capillary and venous blood vessels of the cerebral microvascular bed as well as brain tissue occupying the extravascular space. Microvessels were assembled with optimization algorithms emulating angiogenic growth; a realistic capillary bed was built with space filling procedures. The extravascular tissue was modeled as a porous medium supplied with oxygen by advection–diffusion to match normal metabolic oxygen demand. The resulting synthetic computer generated network matches prior measured morphometrics and fractal patterns of the cortical microvasculature. This morphologically accurate, physiologically consistent, multi-scale computer network of the cerebral microcirculation predicts the oxygen exchange of cortical blood vessels with the surrounding gray matter. Oxygen tension subject to blood pressure and flow conditions were computed and validated for the blood as well as brain tissue. Oxygen gradients along arterioles, capillaries and veins agreed with in vivo trends observed recently in imaging studies within experimental tolerances and uncertainty. PMID:23842693

Transmural Variation and Anisotropy of Microvascular Flow Conductivity in the Rat Myocardium

KAUST Repository

Smith, Amy F.

2014-05-28

Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modeling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the "longitudinal" direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium.

Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

Science.gov (United States)

Salmon, Andrew H J; Satchell, Simon C

2012-03-01

Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function

The maternal brain and its plasticity in humans

Science.gov (United States)

Kim, Pilyoung; Strathearn, Lane; Swain, James E.

2015-01-01

Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

Immunohistochemical study of N-epsilon-carboxymethyl lysine (CML in human brain: relation to vascular dementia

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Williams Jonathan

2007-10-01

Full Text Available Abstract Background Advanced glycation end-products (AGEs and their receptor (RAGE occur in dementia of the Alzheimer's type and diabetic microvascular disease. Accumulation of AGEs relates to risk factors for vascular dementia with ageing, including hypertension and diabetes. Cognitive dysfunction in vascular dementia may relate to microvascular disease resembling that in diabetes. We tested if, among people with cerebrovascular disease, (1 those with dementia have higher levels of neuronal and vascular AGEs and (2 if cognitive dysfunction depends on neuronal and/or vascular AGE levels. Methods Brain Sections from 25 cases of the OPTIMA (Oxford Project to Investigate Memory and Ageing cohort, with varying degrees of cerebrovascular pathology and cognitive dysfunction (but only minimal Alzheimer type pathology were immunostained for Nε-(carboxymethyl-lysine (CML, the most abundant AGE. The level of staining in vessels and neurons in the cortex, white matter and basal ganglia was compared to neuropsychological and other clinical measures. Results The probability of cortical neurons staining positive for CML was higher in cases with worse cognition (p = 0.01 or a history of hypertension (p = 0.028. Additionally, vascular CML staining related to cognitive impairment (p = 0.02 and a history of diabetes (p = 0.007. Neuronal CML staining in the basal ganglia related to a history of hypertension (p = 0.002. Conclusion CML staining in cortical neurons and cerebral vessels is related to the severity of cognitive impairment in people with cerebrovascular disease and only minimal Alzheimer pathology. These findings support the possibility that cerebral accumulation of AGEs may contribute to dementia in people with cerebrovascular disease.

Sleep quality and duration are related to microvascular function: the Amsterdam Growth and Health Longitudinal Study

NARCIS (Netherlands)

Bonsen, T.; Wijnstok, N.J.; Hoekstra, T.; Eringa, E.C.; Serne, E.H.; Smulders, Y.M.; Twisk, J.W.R.

2015-01-01

Sleep and sleep disorders are related to cardiovascular disease, and microvascular function is an early cardiovascular disease marker. Therefore, the relationship of sleep (measured in sleep quality and duration) with microvascular function was examined in healthy adults. Sleep quality was assessed

Uptake of Single-Walled Carbon Nanotubes Conjugated with DNA by Microvascular Endothelial Cells

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Joseph Harvey

2012-01-01

Full Text Available Single-walled carbon nanotubes (SWCNTs have been proposed to have great therapeutic potential. SWCNTs conjugated with drugs or genes travel in the systemic circulation to reach target cells or tissues following extravasation from microvessels although the interaction between SWCNT conjugates and the microvascular endothelial cells (ECs remains unknown. We hypothesized that SWCNT-DNA conjugates would be taken up by microvascular ECs and that this process would be facilitated by SWCNTs compared to facilitation by DNA alone. ECs were treated with various concentrations of SWCNT-DNA-FITC conjugates, and the uptake and intracellular distribution of these conjugates were determined by a confocal microscope imaging system followed by quantitative analysis of fluorescence intensity. The uptake of SWCNT-DNA-FITC conjugates (2 μg/mL by microvascular ECs was significantly greater than that of DNA-FITC (2 μg/mL, observed at 6 hrs after treatment. For the intracellular distribution, SWCNT-DNA-FITC conjugates were detected in the nucleus of ECs, while DNA-FITC was restricted to the cytoplasm. The fluorescence intensity and distribution of SWCNTs were concentration and time independent. The findings demonstrate that SWCNTs facilitate DNA delivery into microvascular ECs, thus suggesting that SWCNTs serving as drug and gene vehicles have therapeutic potential.

Simple instrument for biochemical studies of the living human brain

International Nuclear Information System (INIS)

Bice, A.N.; Wagner, H.N. Jr.; Lee, M.C.; Frost, J.J.

1986-01-01

A simple, relatively inexpensive radiation detection system was developed for measurement of positron-emitting receptor-binding drugs in the human brain. This high-efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of [ 11 C]-carfentanil, a high-affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist exemplifies the use of this system for estimating different degrees of receptor binding of drugs in the human brain. The instrument has also been used for measurement of the transport into the brain of other positron-emitting radiotracers, such as large neutral amino acids

Genome-wide DNA methylation analyses in the brain reveal four differentially methylated regions between humans and non-human primates

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Wang Jinkai

2012-08-01

Full Text Available Abstract Background The highly improved cognitive function is the most significant change in human evolutionary history. Recently, several large-scale studies reported the evolutionary roles of DNA methylation; however, the role of DNA methylation on brain evolution is largely unknown. Results To test if DNA methylation has contributed to the evolution of human brain, with the use of MeDIP-Chip and SEQUENOM MassARRAY, we conducted a genome-wide analysis to identify differentially methylated regions (DMRs in the brain between humans and rhesus macaques. We first identified a total of 150 candidate DMRs by the MeDIP-Chip method, among which 4 DMRs were confirmed by the MassARRAY analysis. All 4 DMRs are within or close to the CpG islands, and a MIR3 repeat element was identified in one DMR, but no repeat sequence was observed in the other 3 DMRs. For the 4 DMR genes, their proteins tend to be conserved and two genes have neural related functions. Bisulfite sequencing and phylogenetic comparison among human, chimpanzee, rhesus macaque and rat suggested several regions of lineage specific DNA methylation, including a human specific hypomethylated region in the promoter of K6IRS2 gene. Conclusions Our study provides a new angle of studying human brain evolution and understanding the evolutionary role of DNA methylation in the central nervous system. The results suggest that the patterns of DNA methylation in the brain are in general similar between humans and non-human primates, and only a few DMRs were identified.

Microvascular filtration is increased in the forearms of patients with breast cancer-related lymphedema

DEFF Research Database (Denmark)

Jensen, Mads Radmer; Simonsen, Lene; Karlsmark, Tonny

2013-01-01

-enhanced ultrasound; venous occlusion strain-gauge plethysmography; lower-body negative pressure; noninvasive blood pressure measurements; and skin (99m)Tc-pertechnetate clearance technique. Measurements were performed bilaterally and simultaneously in the forearms, enabling use of the nonedematous forearm...... relative microvascular volume, forearm blood flow, skin blood flow, or central or local sympathetic vascular reflexes. Forearm microvascular filtration is increased in patients with BCRL, and more so in the edematous arm. The vascular sympathetic control mechanisms seem to be preserved. We propose...... with unilateral BCRL, the following aspects of upper extremity peripheral circulation were examined: muscle relative microvascular volume; capillary filtration coefficient; central and local sympathetic vascular reflexes; skin blood flow; and forearm blood flow. These were studied via real-time, contrast...

Enhanced Local Skeletal Muscle Oxidative Capacity and Microvascular Blood Flow Following 7-Day Ischemic Preconditioning in Healthy Humans

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Owen Jeffries

2018-05-01

Full Text Available Ischemic preconditioning (IPC, which involves intermittent periods of ischemia followed by reperfusion, is an effective clinical intervention that reduces the risk of myocardial injury and confers ischemic tolerance to skeletal muscle. Repeated bouts of IPC have been shown to stimulate long-term changes vascular function, however, it is unclear what metabolic adaptations may occur locally in the muscle. Therefore, we investigated 7 days of bilateral lower limb IPC (4 × 5 min above limb occlusion pressure (220 mmHg; n = 10, or sham (20 mmHg; n = 10, on local muscle oxidative capacity and microvascular blood flow. Oxidative capacity was measured using near-infrared spectroscopy (NIRS during repeated short duration arterial occlusions (300 mmHg. Microvascular blood flow was assessed during the recovery from submaximal isometric plantar flexion exercises at 40 and 60% of maximal voluntary contraction (MVC. Following the intervention period, beyond the late phase of protection (72 h, muscle oxidative recovery kinetics were speeded by 13% (rate constant pre 2.89 ± 0.47 min-1 vs. post 3.32 ± 0.69 min-1; P < 0.05 and resting muscle oxygen consumption (mO2 was reduced by 16.4% (pre 0.39 ± 0.16%.s-1 vs. post 0.33 ± 0.14%.s-1; P < 0.05. During exercise, changes in deoxygenated hemoglobin (HHb from rest to steady state were reduced at 40 and 60% MVC (16 and 12%, respectively, P < 0.05 despite similar measures of total hemoglobin (tHb. At the cessation of exercise, the time constant for recovery in oxygenated hemoglobin (O2Hb was accelerated at 40 and 60% MVC (by 33 and 43%, respectively suggesting enhanced reoxygenation in the muscle. No changes were reported for systemic measures of resting heart rate or blood pressure. In conclusion, repeated bouts of IPC over 7 consecutive days increased skeletal muscle oxidative capacity and microvascular muscle blood flow. These findings are consistent with enhanced mitochondrial and vascular function following

An Integrated Neuroscience and Engineering Approach to Classifying Human Brain-States

Science.gov (United States)

2015-12-22

AFRL-AFOSR-VA-TR-2016-0037 An Integrated Neuroscience and Engineering Approach to Classifying Human Brain-States Adrian Lee UNIVERSITY OF WASHINGTON...to 14-09-2015 4. TITLE AND SUBTITLE An Integrated Neuroscience and Engineering Approach to Classifying Human Brain- States 5a.  CONTRACT NUMBER 5b...specific cognitive states remains elusive, owing perhaps to limited crosstalk between the fields of neuroscience and engineering. Here, we report a

Radioisotope albumin flux measurement of microvascular lung permeability: an independent parameter in acute respiratory failure?

International Nuclear Information System (INIS)

Hoegerle, S.; Nitzsche, E.U.; Reinhardt, M.J.; Moser, E.; Benzing, A.; Geiger, K.; Schulte Moenting, J.

2001-01-01

Aim: To evaluate the extent to which single measurements of microvascular lung permeability may be relevant as an additional parameter in a heterogenous clinical patient collective with Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). Methods: In 36 patients with pneumonia (13), non pneumogenic sepsis (9) or trauma (14) meeting the consensus conference criteria of ALI or ARDS double-isotope protein flux measurements ( 51 Cr erythrocytes as intravascular tracer, Tc-99m human albumin as diffusible tracer) of microvascular lung permeability were performed using the Normalized Slope Index (NSI). The examination was to determine whether there is a relationship between the clinical diagnosis of ALI/ARDS, impaired permeability and clinical parameters, that is the underlying disease, oxygenation, duration of mechanical ventilation and mean pulmonary-artery pressure (PAP). Results: At the time of study, 25 patients presented with increased permeability (NSI > 1 x 10 -3 min -1 ) indicating an exudative stage of disease, and 11 patients with normal permeability. The permeability impairment correlated with the underlying disease (p > 0.05). With respect to survival, there was a negative correlation to PAP (p [de

Main-, minor- and trace elements distribution in human brain

International Nuclear Information System (INIS)

Zoeger, N.; Streli, C.; Wobrauschek, P.; Jokubonis, C.; Pepponi, G.; Roschger, P.; Bohic, S.; Osterode, W.

2004-01-01

Lead (Pb) is known to induce adverse health effects in humans. In fact, cognitive deficits are repeatedly described with Pb exposure, but little is known about the distribution of lead in brain. Measurements of the distribution of Pb in human brain and to study if Pb is associated with the distribution of other chemical elements such as zinc (Zn), iron (Fe) is of great interest and could reveal some hints about the metabolism of Pb in brain. To determine the local distribution of lead (Pb) and other trace elements x-ray fluorescence spectroscopy (XRF) measurements have been performed, using a microbeam setup and highest flux synchrotron radiation. Experiments have been carried out at ID-22, ESRF, Grenoble, France. The installed microprobe setup provides a monochromatic beam (17 keV) from an undulator station focused by Kirkpatrick-Baez x-ray optics to a spot size of 5 μm x 3μm. Brain slices (20 μm thickness, imbedded in paraffin and mounted on Kapton foils) from areas of the frontal cortex, thalamus and hippocampus have been investigated. Generally no significant increase in fluorescence intensities could be detected in one of the investigated brain compartments. However Pb and other (trace) elements (e.g. S, Ca, Fe, Cu, Zn, Br) could be detected in all samples and showed strong inhomogeneities across the analyzed areas. While S, Ca, Fe, Cu, Zn and Br could be clearly assigned to the investigated brain structures (vessels, etc.) Pb showed a very different behavior. In some cases (e.g. plexus choroidei) Pb was located at the walls of the vessel, whereas with other structures (e.g. blood vessel) this correlation was not found. Moreover, the detected Pb in different brain areas was individually correlated with various elements. The local distribution of the detected elements in various brain structures will be discussed in this work. (author)

Characterization of the melanoma brain metastatic niche in mice and humans

International Nuclear Information System (INIS)

Amit, Moran; Laider-Trejo, Leonor; Shalom, Vardit; Shabtay-Orbach, Ayelet; Krelin, Yakov; Gil, Ziv

2013-01-01

Brain metastases occur in 15% of patients with melanoma and are associated with a dismal prognosis. Here, we investigate the architectural phenotype and stromal reaction of melanoma brain metastasis in mice and humans. A syngeneic, green fluorescence protein (GFP)-expressing murine B16-F1 melanoma clone was introduced via intracardiac injection, and was examined in vivo in comparison with human specimens. Immunofluorescence analyses of the brain metastases revealed that F4/80 + macrophages/microglia were most abundant at the tumor front, but rare in its core, where they were found only around blood vessels (P = 0.01). Similar pattern of infiltration was found in CD3 + T cells (P < 0.01). Infiltrating T cells were prominently CD4 + compared with CD8 + T cells (P < 0.001). Blood vessels (CD31 + ) were less abundant at the tumor front than in its center (12 ± 1 vs. 4 ± 0.6 vessels per high-power field [HPF], P < 0.001). In contrast, there were few vessels at the tumor front, but their diameter was significantly larger at the front (8236 μm 2 vs. 4617 μm 2 average cross-sectional area, P < 0.005). This is the first comparative analysis of melanoma brain metastases showing similar stromal reaction in murine models and human specimens. Our results validate the utility of this murine model of melanoma brain metastases for investigating the mechanism of the human disease

Human brain mass: similar body composition associations as observed across mammals.

Science.gov (United States)

Heymsfield, Steven B; Müller, Manfred J; Bosy-Westphal, Anja; Thomas, Diana; Shen, Wei

2012-01-01

A classic association is the link between brain mass and body mass across mammals that has now been shown to derive from fat-free mass (FFM) and not fat mass (FM). This study aimed to establish for the first time the associations between human brain mass and body composition and to compare these relations with those established for liver as a reference organ. Subjects were 112 men and 148 women who had brain and liver mass measured by magnetic resonance imaging with FM and FFM measured by dual-energy X-ray absorptiometry. Brain mass scaled to height (H) with powers of ≤0.6 in men and women; liver mass and FFM both scaled similarly as H(~2) . The fraction of FFM as brain thus scaled inversely to height (P FFM was independent of height. After controlling for age, brain, and liver mass were associated with FFM while liver was additionally associated with FM (all models P ≤ 0.01). After controlling for age and sex, FFM accounted for ~5% of the variance in brain mass while levels were substantially higher for liver mass (~60%). Brain mass was significantly larger (P FFM. As across mammals, human brain mass associates significantly, although weakly, with FFM and not FM; the fraction of FFM as brain relates inversely to height; brain differs in these relations from liver, another small high metabolic rate organ; and the sexual dimorphism in brain mass persists even after adjusting for age and FFM. Copyright © 2012 Wiley Periodicals, Inc.

[Introduction of neuroethics: out of clinic, beyond academia in human brain research].

Science.gov (United States)

Fukushi, Tamami; Sakura, Osamu

2008-11-01

Higher cognitive function in human brain is one of well-developed fields of neuroscience research in the 21st century. Especially functional magnetic resonance imaging (fMRI) and near infrared recording system have brought so many non-clinical researchers whose background is such as cognitive psychology, economics, politics, pedagogy, and so on, to the human brain mapping study. Authors have introduced the ethical issues related to incidental findings during the fMRI recording for non-clinical purpose, which is a typical problem derived from such expanded human brain research under non clinical condition, that is, neuroethics. In the present article we would introduce neuroethical issues in contexts of "out of clinic" and "beyond academia".

Unveiling the mystery of visual information processing in human brain.

Science.gov (United States)

Diamant, Emanuel

2008-08-15

It is generally accepted that human vision is an extremely powerful information processing system that facilitates our interaction with the surrounding world. However, despite extended and extensive research efforts, which encompass many exploration fields, the underlying fundamentals and operational principles of visual information processing in human brain remain unknown. We still are unable to figure out where and how along the path from eyes to the cortex the sensory input perceived by the retina is converted into a meaningful object representation, which can be consciously manipulated by the brain. Studying the vast literature considering the various aspects of brain information processing, I was surprised to learn that the respected scholarly discussion is totally indifferent to the basic keynote question: "What is information?" in general or "What is visual information?" in particular. In the old days, it was assumed that any scientific research approach has first to define its basic departure points. Why was it overlooked in brain information processing research remains a conundrum. In this paper, I am trying to find a remedy for this bizarre situation. I propose an uncommon definition of "information", which can be derived from Kolmogorov's Complexity Theory and Chaitin's notion of Algorithmic Information. Embracing this new definition leads to an inevitable revision of traditional dogmas that shape the state of the art of brain information processing research. I hope this revision would better serve the challenging goal of human visual information processing modeling.

Steady-state cerebral glucose concentrations and transport in the human brain

OpenAIRE

Gruetter, R.; Ugurbil, K.; Seaquist, E. R.

1998-01-01

Understanding the mechanism of brain glucose transport across the blood- brain barrier is of importance to understanding brain energy metabolism. The specific kinetics of glucose transport nave been generally described using standard Michaelis-Menten kinetics. These models predict that the steady- state glucose concentration approaches an upper limit in the human brain when the plasma glucose level is well above the Michaelis-Menten constant for half-maximal transport, K(t). In experiments wh...

Information flow between interacting human brains: Identification, validation, and relationship to social expertise.

Science.gov (United States)

Bilek, Edda; Ruf, Matthias; Schäfer, Axel; Akdeniz, Ceren; Calhoun, Vince D; Schmahl, Christian; Demanuele, Charmaine; Tost, Heike; Kirsch, Peter; Meyer-Lindenberg, Andreas

2015-04-21

Social interactions are fundamental for human behavior, but the quantification of their neural underpinnings remains challenging. Here, we used hyperscanning functional MRI (fMRI) to study information flow between brains of human dyads during real-time social interaction in a joint attention paradigm. In a hardware setup enabling immersive audiovisual interaction of subjects in linked fMRI scanners, we characterize cross-brain connectivity components that are unique to interacting individuals, identifying information flow between the sender's and receiver's temporoparietal junction. We replicate these findings in an independent sample and validate our methods by demonstrating that cross-brain connectivity relates to a key real-world measure of social behavior. Together, our findings support a central role of human-specific cortical areas in the brain dynamics of dyadic interactions and provide an approach for the noninvasive examination of the neural basis of healthy and disturbed human social behavior with minimal a priori assumptions.

Human Brain Organoids on a Chip Reveal the Physics of Folding.

Science.gov (United States)

Karzbrun, Eyal; Kshirsagar, Aditya; Cohen, Sidney R; Hanna, Jacob H; Reiner, Orly

2018-05-01

Human brain wrinkling has been implicated in neurodevelopmental disorders and yet its origins remain unknown. Polymer gel models suggest that wrinkling emerges spontaneously due to compression forces arising during differential swelling, but these ideas have not been tested in a living system. Here, we report the appearance of surface wrinkles during the in vitro development and self-organization of human brain organoids in a micro-fabricated compartment that supports in situ imaging over a timescale of weeks. We observe the emergence of convolutions at a critical cell density and maximal nuclear strain, which are indicative of a mechanical instability. We identify two opposing forces contributing to differential growth: cytoskeletal contraction at the organoid core and cell-cycle-dependent nuclear expansion at the organoid perimeter. The wrinkling wavelength exhibits linear scaling with tissue thickness, consistent with balanced bending and stretching energies. Lissencephalic (smooth brain) organoids display reduced convolutions, modified scaling and a reduced elastic modulus. Although the mechanism here does not include the neuronal migration seen in in vivo , it models the physics of the folding brain remarkably well. Our on-chip approach offers a means for studying the emergent properties of organoid development, with implications for the embryonic human brain.

In Vivo H MR spectroscopic imaging of human brain

International Nuclear Information System (INIS)

Choe, Bo Young; Suh, Tae Suk; Choi, Kyo Ho; Bahk, Yong Whee; Shinn, Kyung Sub

1994-01-01

To evaluate the spatial distribution of various proton metabolites in the human brain with use of water-suppressed in vivo H MR spectroscopic imaging (MRSI) technique. All of water-suppressed in vivo H MRSI were performed on 1.5 T whole-body MRI/MRS system using Stimulated Echo Acquisition Method (STEAM) Chemical Shift Imaging (CSI) pulse sequence. T1-weighted MR images were used for CSI field of view (FOV; 24 cm). Voxel size of 1.5 cm 3 was designated from the periphery of the brain which was divided by 1024 X 16 X 16 data points. Metabolite images of N-acetylaspartate (NAA), creatine/ phosphocreatine (Cr) + choline/phosphocholine (Cho), and complex of γ-aminobutyric acid (GABA) + glutamate (Glu) were obtained on the human brain. Our preliminary study suggests that in vivo H MRSI could provide the metabolite imaging to compensate for hypermetabolism on Positron Emission Tomography (PET) scans on the basis of the metabolic informations on brain tissues. The unique ability of in vivo H MRSI to offer noninvasive information about tissue biochemistry in disease states will stimulate on clinical research and disease diagnosis

The role of positron emission tomography in neuropharmacology in the living human brain and drug development

International Nuclear Information System (INIS)

Yanai, Kazuhiko

1999-01-01

Neuroimaging is a powerful and innovative tool for studying the pathology of psychiatric and neurological diseases and, more recently, for studying the drugs used in their treatment. Technological advances in imaging have made it possible to noninvasively extract information from the human brain regarding a drug's mechanism and site of action. Until now, our understanding of human brain pharmacology has depended primarily on indirect assessments or models derived from animal studies. However, the advent of multiple techniques for human brain imaging allows researchers to focus directly on human pharmacology and brain function. In this review article, our PET studies on the histaminergic neuron system were presented as an example. We have developed and used the PET techniques for 10 years in order to examine the H 1 receptors in the living human brain. This review outlines available PET techniques and examine how these various methods have already been applied to the drug development process and neuropharmacology in the living human brain. (author)

The role of positron emission tomography in neuropharmacology in the living human brain and drug development

Energy Technology Data Exchange (ETDEWEB)

Yanai, Kazuhiko [Tohoku Univ., Sendai (Japan). School of Medicine

1999-09-01

Neuroimaging is a powerful and innovative tool for studying the pathology of psychiatric and neurological diseases and, more recently, for studying the drugs used in their treatment. Technological advances in imaging have made it possible to noninvasively extract information from the human brain regarding a drug's mechanism and site of action. Until now, our understanding of human brain pharmacology has depended primarily on indirect assessments or models derived from animal studies. However, the advent of multiple techniques for human brain imaging allows researchers to focus directly on human pharmacology and brain function. In this review article, our PET studies on the histaminergic neuron system were presented as an example. We have developed and used the PET techniques for 10 years in order to examine the H{sub 1} receptors in the living human brain. This review outlines available PET techniques and examine how these various methods have already been applied to the drug development process and neuropharmacology in the living human brain. (author)

The influence of heroin abuse on glutathione-dependent enzymes in human brain.

Science.gov (United States)

Gutowicz, Marzena; Kaźmierczak, Beata; Barańczyk-Kuźma, Anna

2011-01-01

Heroin is an illicit narcotic abused by millions of people worldwide. In our earlier studies we have shown that heroin intoxication changes the antioxidant status in human brain. In the present work we continued our studies by estimating the effect of heroin abuse on reduced glutathione (GSH) and enzymes related to this cofactor, such as glutathione S-transferase detoxifying electrophilics (GST) and organic peroxides (as Se-independent glutathione peroxidase-GSHPx), and Se-dependent glutathione peroxidase (Se-GSHPx) specific mainly for hydrogen peroxide. Studies were conducted on human brains obtained from autopsy of 9 heroin abusers and 8 controls. The level of GSH and the activity of glutathione-related enzymes were determined spectrophotometrically. The expression of GST pi on mRNA and protein level was studied by RT-PCR and Western blotting, respectively. The results indicated significant increase of GST and GSHPx activities, unchanged Se-GSHPx activity, and decreased level of GSH in frontal, temporal, parietal and occipital cortex, brain stem, hippocampus, and white matter of heroin abusers. GST pi expression was increased on both mRNA and protein levels, however the increase was lower in brain stem than in other regions. Heroin affects all regions of human brain, and especially brain stem. Its intoxication leads to an increase of organic rather then inorganic peroxides in various brain regions. Glutathione S-transferase plays an important role during heroin intoxication, however its protective effect is lower in brain stem than in brain cortex or hippocampus. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Microvascularization on collared peccary placenta

DEFF Research Database (Denmark)

Santos, Tatiana Carlesso; Oliveira, Moacir Franco; Dantzer, Vibeke

2012-01-01

and fetal compartments of the placentae. The immunolocalization of vimentin in the vascular endothelium and in the smooth muscle cells of blood vessels showed indented capillaries along the uterine epithelium and the trophoblast at the sides of complementary maternal and fetal microfolds, or rugae...... into a microvascular network wall in a basket-like fashion. At the base of these baskets venules were formed. On the fetal side, arterioles branched centrally in the fetal rugae into a capillary network in a bulbous form, complementary to the opposite maternal depressions forming the baskets. At the base...

A new method to study changes in microvascular blood volume in muscle and adipose tissue: Real time imaging in humans and rat

DEFF Research Database (Denmark)

Sjøberg, Kim Anker; Rattigan, Stephen; Hiscock, Natalie J

2011-01-01

We employed and evaluated a new application of contrast enhanced ultrasound for real time imaging of changes in microvascular blood volume (MVB) in tissues in females, males and rat. Continuous real time imaging was performed using contrast enhanced ultrasound to quantify infused gas filled micro...

The human sexual response cycle : Brain imaging evidence linking sex to other pleasures

NARCIS (Netherlands)

Georgiadis, J. R.; Kringelbach, M. L.

Sexual behavior is critical to species survival, yet comparatively little is known about the neural mechanisms in the human brain. Here we systematically review the existing human brain imaging literature on sexual behavior and show that the functional neuroanatomy of sexual behavior is comparable

Microvascular Architecture of Hepatic Metastases in a Mouse Model

Directory of Open Access Journals (Sweden)

Darshini Kuruppu

1997-01-01

Full Text Available Development of effective treatment for hepatic metastases can be initiated by a better understanding of tumour vasculature and blood supply. This study was designed to characterise the microvascular architecture of hepatic metastases and observe the source of contributory blood supply from the host. Metastases were induced in mice by an intrasplenic injection of colon carcinoma cells (106 cells/ml. Vascularization of tumours was studied over a three week period by scanning electron microscopy of microvascular corrosion casts. Metastatic liver involvement was observed initially within a week post induction, as areas approximately 100 μm in diameter not perfused by the casting resin. On histology these spaces corresponded to tumour cell aggregates. The following weeks highlighted the angiogenesis phase of these tumours as they received a vascular supply from adjacent hepatic sinusoids. Direct sinusoidal supply of metastases was maintained throughout tumour growth. At the tumour periphery most sinusoids were compressed to form a sheath demarcating the tumour from the hepatic vasculature. No direct supply from the hepatic artery or the portal vein was observed. Dilated vessels termed vascular lakes dominated the complex microvascular architecture of the tumours, most tapering as they traversed towards the periphery. Four vascular branching patterns could be identified as true loops, bifurcations and trifurcations, spirals and capillary networks. The most significant observation in this study was the direct sinusoidal supply of metastases, together with the vascular lakes and the peripheral sinusoidal sheaths of the tumour microculature.

Skull and cerebrospinal fluid effects on microwave radiation propagation in human brain

Science.gov (United States)

Ansari, M. A.; Zarei, M.; Akhlaghipour, N.; Niknam, A. R.

2017-12-01

The determination of microwave absorption distribution in the human brain is necessary for the detection of brain tumors using thermo-acoustic imaging and for removing them using hyperthermia treatment. In contrast to ionizing radiation, hyperthermia treatment can be applied to remove tumors inside the brain without the concern of including secondary malignancies, which typically form from the neuronal cells of the septum pellucidum. The aim of this study is to determine the microwave absorption distribution in an adult human brain and to study the effects of skull and cerebrospinal fluid on the propagation of microwave radiation inside the brain. To this end, we simulate the microwave absorption distribution in a realistic adult brain model (Colin 27) using the mesh-based Monte Carlo (MMC) method. This is because in spite of there being other numerical methods, the MMC does not require a large memory, even for complicated geometries, and its algorithm is simple and easy to implement with low computational cost. The brain model is constructed using high-resolution (1 mm isotropic voxel) and low noise magnetic resonance imaging (MRI) scans and its volume contains 181×217×181 voxels, covering the brain completely. Using the MMC method, the radiative transport equation is solved and the absorbed microwave energy distribution in different brain regions is obtained without any fracture or anomaly. The simulation results show that the skull and cerebrospinal fluid guide the microwave radiation and suppress its penetration through deep brain compartments as a shielding factor. These results reveal that the MMC can be used to predict the amount of required energy to increase the temperature inside the tumour during hyperthermia treatment. Our results also show why a deep tumour inside an adult human brain cannot be efficiently treated using hyperthermia treatment. Finally, the accuracy of the presented numerical method is verified using the signal flow graph technique.

Automated Measurement Of The Density Of Vessels On Whole Slide Images Of Paediatric Brain Tumours

Directory of Open Access Journals (Sweden)

Christophe Deroulers

2016-06-01

Only a few parameters have to be chosen, once and for all samples (e.g., the minimal acceptable size of a blood vessel fragment, which makes the method more robust than assessment by a (panel of human expert(s. The automatic calibration steps enable one to deal with a heterogeneous set of slides (e.g., slight differences in background colour and staining. The method uses only open-source software. It is easy to extend or improve and not tight to a single immunomarker. We applied the method to 129 paediatric brain tumours of 8 different types and 3 locations (posterior fossa, thalamus, hemispheres — 185 samples in total. For each patient, the density of microvessels in the sample is compared to the cerebral blood flow as assessed by preoperative perfusion-weighted-imaging using arterial-spin-labeling. We find a good correlation between microvascular density, MRI data and tumour grading. The microvascular density is broadly distributed among the samples. Visualisation in a web browser is slightly more fluid when images are uploaded in the DeepZoom format rather than as pyramidal TIFF images, but the former consumes roughly 20 times more disk space and needs the transfer of a very large number of files after each modification, which is less tractable.

Brain barriers and functional interfaces with sequential appearance of ABC efflux transporters during human development

DEFF Research Database (Denmark)

Møllgård, Kjeld; Dziegielewska, Katarzyna M.; Holst, Camilla B.

2017-01-01

Adult brain is protected from entry of drugs and toxins by specific mechanisms such as ABC (ATP-binding Cassette) efflux transporters. Little is known when these appear in human brain during development. Cellular distribution of three main ABC transporters (ABCC1, ABCG2, ABCB1) was determined...... at blood-brain barriers and interfaces in human embryos and fetuses in first half of gestation. Antibodies against claudin-5 and-11 and antibodies to α-fetoprotein were used to describe morphological and functional aspects of brain barriers. First exchange interfaces to be established, probably at 4...... three transporters. Results provide evidence for sequential establishment of brain exchange interfaces and spatial and temporal timetable for three main ABC transporters in early human brain....

Impact of an endothelial progenitor cell capturing stent on coronary microvascular function: comparison with drug-eluting stents.

Science.gov (United States)

Choi, Woong Gil; Kim, Soo Hyun; Yoon, Hyung Seok; Lee, Eun Joo; Kim, Dong Woon

2015-01-01

Although drug-eluting stents (DESs) effectively reduce restenosis following percutaneous coronary intervention (PCI), they also delay re-endothelialization and impair microvascular function, resulting in adverse clinical outcomes. Endothelial progenitor cell (EPC) capturing stents, by providing a functional endothelial layer on the stent, have beneficial effects on microvascular function. However, data on coronary microvascular function in patients with EPC stents versus DESs are lacking. Seventy-four patients who previously underwent PCI were enrolled in this study. Microvascular function was evaluated 6 months after PCI based on the index of microvascular resistance (IMR) and the coronary flow reserve (CFR). IMR was calculated as the ratio of the mean distal coronary pressure at maximal hyperemia to the inverse of the hyperemic mean transit time (hTmn). The CFR was calculated by dividing the hTmn by the baseline mean transit time. Twenty-one patients (age, 67.2 ± 9.6 years; male:female, 15:6) with an EPC stent and 53 patients (age, 61.5 ± 14.7 years; male:female, 40:13) with second-generation DESs were included in the study. There were no significant differences in the baseline clinical and angiographic characteristics of the two groups. Angiography performed 6 months postoperatively did not show significant differences in their CFR values. However, patients with the EPC stent had a significantly lower IMR than patients with second-generation DESs (median, 25.5 [interquartile range, 12.85 to 28.18] vs. 29.0 [interquartile range, 15.42 to 39.23]; p = 0.043). Microvascular dysfunction was significantly improved after 6 months in patients with EPC stents compared to those with DESs. The complete re-endothelialization achieved with the EPC stent may provide clinical benefits over DESs, especially in patients with microvascular dysfunction.

Conflicting interactions of apolipoprotein A and high density lipoprotein cholesterol with microvascular complications of type 2 diabetes.

Science.gov (United States)

Aryan, Zahra; Afarideh, Mohsen; Ghajar, Alireza; Esteghamati, Sadaf; Esteghamati, Alireza; Nakhjavani, Manouchehr

2017-11-01

This study is amid at investigating the associations, and interactions of serum lipid biomarkers with microvascular complications of type 2 diabetes (T2D). A nested case-control study was conducted within an ongoing prospective study on patients with T2D. Microvascular complications of T2D including diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were investigated. A total of 444 cases with at least one of the microvascular complications of T2D and 439 age- and gender-matched controls free of any of the chronic microvascular complications of T2D were included. The associations and interactions of a panel of serum lipid biomarkers with the microvascular complications of T2D were investigated. Serum triglyceride had the strongest association with microvascular complications of T2D (crude model: β=0.632, P value=0.045). Each standard deviation increment in serum TG was associated with 3.7 times increased frequency of microvascular complications. Despite high density lipoprotein cholesterol (HDL-C), serum apolipoprotein A1 (Apo A1) was positively associated with the presence of diabetic neuropathy. Each standard deviation increment in serum ApoA1 was associated with increased frequency of diabetic neuropathy (OR, 1.2, 95% CI, (1.1-1.3), P value=0.006). The frequency of diabetic neuropathy was higher in 2nd and 3rd quartiles of serum Lp(a) compared to diabetic patients in the first quartile (OR, 5.52, 95% (1.17-25.8), P value=0.047). ApoA1 but not HDL-C is straightly associated with diabetic neuropathy. Even Slight rise in serum Lp(a) is associated with increased frequency of diabetic retinopathLipid variables could serve as specific predictors of vascular complications in diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.