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Examines cerebral blood flow measurement. Recognition on the significance of the blood supply to the brain by the Greeks in early times; Elucidation that pressure on the vessels of the neck resulted in anesthesia sufficient to carry out certain surgical procedures; Development of techniques for the examination of the pial vessels; Focus of scientific investigations on the physiological aspects of the brain blood supply.

Careful examination of relevant literature shows that many of the most cherished concepts of the blood-brain barrier are incorrect. These include an almost mythological belief in its immaturity that is unfortunately often equated with absence or at least leakiness in the embryo and fetus. The original concept of a blood-brain barrier is often attributed to Ehrlich; however, he did not accept that permeability of cerebral vessels was different from other organs. Goldmann is often credited with the first experiments showing dye (trypan blue) exclusion from the brain when injected systemically, but not when injected directly into it. Rarely cited are earlier experiments of Bouffard and of Franke who showed methylene blue and trypan red stained all tissues except the brain. The term "blood-brain barrier" "Blut-Hirnschranke" is often attributed to Lewandowsky, but it does not appear in his papers. The first person to use this term seems to be Stern in the early 1920s. Studies in embryos by Stern and colleagues, Weed and Wislocki showed results similar to those in adult animals. These were well-conducted experiments made a century ago, thus the persistence of a belief in barrier immaturity is puzzling. As discussed in this review, evidence for this belief, is of poor experimental quality, often misinterpreted and often not properly cited. The functional state of blood-brain barrier mechanisms in the fetus is an important biological phenomenon with implications for normal brain development. It is also important for clinicians to have proper evidence on which to advise pregnant women who may need to take medications for serious medical conditions. Beliefs in immaturity of the blood-brain barrier have held the field back for decades. Their history illustrates the importance of taking account of all the evidence and assessing its quality, rather than selecting papers that supports a preconceived notion or intuitive belief. This review attempts to right the wrongs. Based on careful translation of original papers, some published a century ago, as well as providing discussion of studies claiming to show barrier immaturity, we hope that readers will have evidence on which to base their own conclusions. [ABSTRACT FROM AUTHOR]

The connection between the nasal cavity and the CNS by the olfactory neurones has been investigated extensively during the last decades with regard to its feasibility to serve as a direct drug transport route to the CSF and brain. This drug transport route has gained much interest as it may circumvent the blood-brain barrier (BBB), which prevents some drugs from entering the brain. Approximately 100 published papers mainly reporting animal experiments were reviewed to evaluate whether the experimental design used and the results generated provided adequate pharmacokinetic information to assess whether the investigated drug was transported directly from the olfactory area to the CNS. In the analysis the large anatomical differences between the olfactory areas of animals and humans and the experimental conditions used were evaluated. The aim of this paper was to establish the actual evidence for the feasibility of this direct transport route in humans. Twelve papers presented a sound experimental design to study direct nose to CNS transport of drugs based on the authors' criteria. Of these, only two studies in rats were able to provide results that can be seen as an indication for direct transport from the nose to the CNS. No pharmacokinetic evidence could be found to support a claim that nasal administration of drugs in humans will result in an enhanced delivery to their target sites in the brain compared with intravenous administration of the same drug under similar dosage conditions. [ABSTRACT FROM AUTHOR]

This paper describes the results of intraoperational monitoring of hemodynamic parameters (velocity and pressure) in brain vessels, carried out within the framework of 50 neurosurgical operations using a Volcano ComboMap instrumental measuring system. It is established that the introduced parameter of specific load used during the neurosurgical operations is a significant parameter for the success of the operation. [ABSTRACT FROM AUTHOR]

Subdural hematomas are one of the frequent complications of head injuries. Such hematomas result from exceeding the border strength values of bridging veins. Subdural haemorrhages are life-threatening and are a frequent cause of considerable pathologies. Traffic participants and also soldiers who participate in armed conflicts are the most vulnerable to head injuries. Although hematomas have been studied for many years the mechanism of hematoma formation has not been fully clarified as yet. In the paper, the effort of brain tissue structures due to the propagation of shock wave was analyzed. Particular attention was paid to the deformation ability and changes in the energy of bridging veins. This research was concerned with changes in mechanical properties of these veins in the frontal, parietal and occipital regions of the brain. For the present research the authors have constructed finite element models of brain tissue fragments and conducted numerical studies taking into account the boundary conditions arising from violent overloads that result from combat operations. As a result of the numerical analysis conducted, critical values of strain and stress have been obtained. The analysis showed high diversity in the properties of the different regions of the brain tissue. The studies carried out by the authors rendered it possible to assess the effort of the tissue structures of veins in connection with mechanical parameters, including geometrical parameters, in particular in relation to the likelihood of hematoma formation. [ABSTRACT FROM AUTHOR]

Current neuroimaging techniques with high spatial resolution constrain participant motion so that many natural tasks cannot be carried out. The aim of this paper is to show how a time-locked correlation-analysis of cerebral blood flow velocity (CBFV) lateralisation data, obtained with functional TransCranial Doppler (fTCD) ultrasound, can be used to infer cerebral activation patterns across tasks. In a first experiment we demonstrate that the proposed analysis method results in data that are comparable with the standard Lateralisation Index (LI) for within-task comparisons of CBFV patterns, recorded during cued word generation (CWG) at two difficulty levels. In the main experiment we demonstrate that the proposed analysis method shows correlated bloodflow patterns for two different cognitive tasks that are known to draw on common brain areas, CWG and Music Synthesis. We show that CBFV patterns for Music and CWG are correlated only for participants with prior musical training. CBFV patterns for tasks that draw on distinct brain areas, the Tower of London and CWG, are not correlated. The proposed methodology extends conventional fTCD analysis by including temporal information in the analysis of cerebral blood-flow patterns to provide a robust, non-invasive method to infer whether common brain areas are used in different cognitive tasks. It complements conventional high resolution imaging techniques. [ABSTRACT FROM AUTHOR]

Isolated symptomatic occlusion of the anterior cerebral artery (ACA) is a rare condition and until date, only few cases regarding the revascularization of the ACA have been reported. This paper reports on successful attempt to revascularize the ACA using superficial temporal artery (STA) in patient with isolated symptomatic occlusion of the ACA. A 69-year-old man presented with several episodes of transient weakness involving left lower extremity. Cerebral angiography showed occlusion of the right ACA at the A2 segment. After medical treatment failure, the patient underwent STAACA bypass surgery. Subsequent to surgery, there was immediate disappearance of transient ischemic attack and follow-up angiography showed favorable revascularization of the ACA territory. Bypass surgery can be considered in the patients with symptomatic occlusion of the ACA, who have experienced failure in medical treatment. [ABSTRACT FROM AUTHOR]

Chronic imaging of cerebral blood flow (CBF) is an important tool for investigating vascular remodeling after injury such as stroke. Although techniques such as Laser Speckle Contrast Imaging (LSCI) have emerged as valuable tools for imaging CBF in acute experiments, their utility for chronic measurements or cross-animal comparisons has been limited. Recently, an extension to LSCI called Multi-Exposure Speckle Imaging (MESI) was introduced that increases the quantitative accuracy of CBF images. In this paper, we show that estimates of chronic blood flow are better with MESI than with traditional LSCI. We evaluate the accuracy of the MESI flow estimates using red blood cell (RBC) photographic tracking as an absolute flow calibration in mice over several days. The flow measures computed using the MESI and LSCI techniques were found to be on average 10% and 24% deviant (n=9 mice), respectively, compared with RBC velocity changes. We also map CBF dynamics after photo-thrombosis of selected cortical microvasculature. Correlations of flow dynamics with RBC tracking were closer with MESI (r=0.88) than with LSCI (r=0.65) up to 2 weeks from baseline. With the increased quantitative accuracy, MESI can provide a platform for studying the efficacy of stroke therapies aimed at flow restoration. [ABSTRACT FROM AUTHOR]

Background: A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood-brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix®) and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design: Two centers will include a total of 600 smokers who are motivated to quit smoking. At week--2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7 days of varenicline treatment at week 1. Smokers will be followed up for 54 weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion: This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of nicotine vaccination for relapse prevention. Trial registration: ClinicalTrials.gov: (NCT00995033) [ABSTRACT FROM AUTHOR]

In multiple sclerosis (MS), compromised blood-brain barrier (BBB) integrity contributes to inflammatory T cell migration into the central nervous system. Matrix metalloproteinase-9 (MMP-9) is associated with BBB disruption and subsequent T cell migration into the CNS. The aim of this paper was to evaluate the effects of omega-3 fatty acids on MMP-9 levels and T cell migration. Peripheral blood mononuclear cells (PBMC) from healthy controls were pretreated with two types of omega-3 fatty acids, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Cell supernatants were used to determine MMP-9 protein and activity levels. Jurkat cells were pretreated with EPA and DHA and were added to fibronectin-coated transwells to measure T cell migration. EPA and DHA significantly decreased MMP-9 protein levels, MMP-9 activity, and significantly inhibited human T cell migration. The data suggest that omega-3 fatty acids may benefit patients with multiple sclerosis by modulating immune cell production of MMP-9. [ABSTRACT FROM AUTHOR]

The linearized filtering approach to the hemodynamic system is limited in capturing the inherent nonlinearities of physiological systems. The nonlinear estimation method therefore should be thought of as a natural way to access the nonlinear data assimilation problem. In this paper, we present a nonlinear filtering algorithm which is computationally expensive compared to the existing linearization filtering algorithms, for hemodynamic data assimilation, to address the deficiencies inherent to linearization. Simultaneous estimation of the physiological states and the system parameters have been demonstrated in a simulated and real data. The method provides more reasonable inference about the parameters of models for hemodynamic data assimilation. [ABSTRACT FROM AUTHOR]

This paper proposes a novel computational methodology for modelling the haemodynamic effects of endovascular coil embolization for cerebral aneurysms. We employ high-resolution 3-D angiographic data to reconstruct the intracranial geometry and we model the coiled part of the aneurysm as a porous medium, with porosity decreasing as coils are inserted. The actual dimensions of the coils employed are used to determine the characteristics of the porous medium. Simulation results for saccular aneurysms from the anterior communicating and middle cerebral arteries show that insertion of coils rapidly changes intraaneurysmal blood flow and causes reduction in mural pressure and blood velocity up to stagnation, providing favorable conditions for thrombus formation and obliteration of the aneurysm. [ABSTRACT FROM AUTHOR]

In most tissues and organs, the lymphatic circulation is responsible for the removal of interstitial protein and fluid but the parenchyma of the brain and spinal cord is devoid of lymphatic vessels. On the other hand, the literature is filled with qualitative and quantitative evidence supporting a lymphatic function in cerebrospinal fluid (CSF) absorption. The experimental data seems to warrant a re-examination of CSF dynamics and consideration of a new conceptual foundation on which to base our understanding of disorders of the CSF system. The objective of this paper is to review the key studies pertaining to the role of the lymphatic system in CSF absorption. [ABSTRACT FROM AUTHOR]

In 1948, Seymour S. Kety and Carl F. Schmidt published back-to-back papers in the JCI that are widely acknowledged as landmarks. Upon publication, the studies resolved a century-old debate, irrefutably demonstrating that cerebral blood flow is regionally regulated. The reported findings turned out to be so powerful in their implications that they provided the inspirational spark that illuminated a brand-new field: functional brain imaging. Thus these papers are landmarks of the rarest kind, not only ending a controversy, but also giving birth to one of the most exciting fields within modern day neuro science. [ABSTRACT FROM AUTHOR]

A new vascular structure segmentation method, which is based on a cylindrical flux-based higher order tensor (HOT), is presented. On a vessel structure, the HOT naturally models branching points, which create challenges for vessel segmentation algorithms. In a general linear HOT model embedded in 3D, one has to work with an even order tensor due to an enforced antipodal-symmetry on the unit sphere. However, in scenarios such as in a bifurcation, the antipodally-symmetric tensor embedded in 3D will not be useful. In order to overcome that limitation, we embed the tensor in 4D and obtain a structure that can model asymmetric junction scenarios. During construction of a higher order tensor (e.g. third or fourth order) in 4D, the orientation vectors lie on the unit 3-sphere, in contrast to the unit 2-sphere in 3D tensor modeling. This 4D tensor is exploited in a seed-based vessel segmentation algorithm, where the principal directions of the 4D HOT is obtained by decomposition, and used in a HOT tractography approach. We demonstrate quantitative validation of the proposed algorithm on both synthetic complex tubular structures as well as real cerebral vasculature in Magnetic Resonance Angiography (MRA) datasets and coronary arteries from Computed Tomography Angiography (CTA) volumes. [ABSTRACT FROM AUTHOR]

The regulatory interplay between laminar shear stress and proinflammatory cytokines during homeostatic maintenance of the brain microvascular endothelium is largely undefined. We hypothesized that laminar shear could counteract the injurious actions of proinflammatory cytokines on human brain microvascular endothelial cell (HBMvEC) barrier properties, in-part through suppression of cellular redox signaling. For these investigations, HBMvECs were exposed to either shear stress (8 dynes/cm2, 24 hours) or cytokines (tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6), 0 to 100 ng/mL, 6 or 18 hours). Human brain microvascular endothelial cell 'preshearing'±cytokine exposure was also performed. Either cytokine dose-dependently decreased expression and increased phosphorylation (pTyr/pThr) of interendothelial occludin, claudin-5, and vascular endothelial-cadherin; observations directly correlating to endothelial barrier reduction, and in precise contrast to effects seen with shear. We further observed that, relative to unsheared cells, HBMvECs presheared for 24 hours exhibited significantly reduced reactive oxygen species production and barrier permeabilization in response to either TNF-α or IL-6 treatment. Shear also downregulated NADPH oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) activation in HBMvECs, as manifested in the reduced expression and coassociation of gp91phox and p47phox. These findings lead us to conclude that physiologic shear can protect the brain microvascular endothelium from injurious cytokine effects on interendothelial junctions and barrier function by regulating the cellular redox state in-part through NADPH oxidase inhibition. [ABSTRACT FROM AUTHOR]

The primary angiitis of the central nervous system (PACNS) is an entity with a very low incidence and prevalence. It is not clear why the inflammatory process of this entity is limited to the cerebral vasculature without systemic manifestations. Its clinical manifestations are very heterogeneous and make clinical diagnosis difficult. In most cases, a brain biopsy is required. Only the clinical suspicion and the ability to recognize the possible clinical and imagenological patterns of presentation make an accurate diagnosis possible. The vast majority of the treatment recommendations are given by series of case reports. The following paper described the clinical, imagenological, and histopathological characteristics of three Colombian patients with PACNS.Thestrategic therapeutic used in shown. [ABSTRACT FROM AUTHOR]

The article focuses on the neural activity regulation of T cells in the blood-brain barrier of a mouse with multiple sclerosis, wherein a gateway in the blood vessel was formed that allows T cells to enter the central nervous system (CNS).

Background: As a continuation of the previous findings in human fetuses, accidental finding of an accessory vascular component in the posterior part of CAC of human adult cadavers inspired the authors to present and compare its posterior part configuration. Case presentation: Examination was carried out on brains of 48 human adult cadavers, routinely dissected at the Institute of Forensic Medicine. The aberrant vessel in the posterior part of four CACs was discovered. Vascular components of the posterior segment of CAC or of the whole CAC were described and photographed. A comparison between fetal and adult cases was also presented. Conclusions: Based on the fact that the age of the four presented cases ranged from 73 to 84 and based on the causes of their death, we concluded that the angioarchitecture of the posterior part of the CAC is a consequence of the embryonic or primitive arterial stabilization and interaction with normal adult vessels. [ABSTRACT FROM AUTHOR]

The negative surface charge of brain microvessel endothelial cells is derived from the special composition of their membrane lipids and the thick endothelial surface glycocalyx. They are important elements of the unique defense systems of the blood–brain barrier. The tissue-specific properties, components, function and charge of the brain endothelial glycocalyx have only been studied in detail in the past 15 years. This review highlights the importance of the negative surface charge in the permeability of macromolecules and nanoparticles as well as in drug interactions. We discuss surface charge and glycoxalyx changes in pathologies related to the brain microvasculature and protective measures against glycocalyx shedding and damage. We present biophysical techniques, including a microfluidic chip device, to measure surface charge of living brain endothelial cells and imaging methods for visualization of surface charge and glycocalyx. [ABSTRACT FROM AUTHOR]

The article discuss studies on the role of pericytes in the blood-brain barrier (BBB) function. The first study showed that a functional BBB is present during embryogenesis while the second study proved that pericytes are essential in BBB regulation. Aside from that, the two research groups also studied how the absence of pericytes cause leakiness and results show that the increased leakiness in the mouse models was caused by increased endothelial transcytosis.

Objective: This study analyzed variability in cerebral blood flow velocity (CBFV) and its association with emotional, clinical and functional variables and medication use in fibromyalgia syndrome (FMS). Methods: Using transcranial Doppler sonography, CBFV were bilaterally recorded in the anterior (ACA) and middle (MCA) cerebral arteries of 44 FMS patients and 31 healthy individuals during a 5-min resting period. Participants also completed questionnaires assessing pain, fatigue, insomnia, anxiety, depression and health-related quality of life (HRQoL). Results: Fast Fourier transformation revealed a spectral profile with four components: (1) a first very low frequency (VLF) component with the highest amplitude at 0.0024 Hz; (2) a second VLF component around 0.01-to-0.025 Hz; (3) a low frequency (LF) component from 0.075-to-0.11 Hz; and (4) a high frequency (HF) component with the lowest amplitude from 0.25-to-0.35 Hz. Compared to controls, FMS patients exhibited lower LF and HF CBFV variability in the MCAs (p < .005) and right ACA (p = .03), but higher variability at the first right MCA (p = .04) and left ACA (p = .005) VLF components. Emotional, clinical and functional variables were inversely related to LF and HF CBFV variability (r≥-.24, p≤.05). However, associations for the first VLF component were positive (r≥.28, p≤.05). While patients´ medication use was associated with lower CBFV variability, comorbid depression and anxiety disorders were unrelated to variability. Conclusions: Lower CBFV variability in the LF and HF ranges were observed in FMS, suggesting impaired coordination of cerebral regulatory systems. CBFV variability was differentially associated with clinical variables as a function of time-scale, with short-term variability being related to better clinical outcomes. CBFV variability analysis may be a promising tool to characterize FMS pathology and it impact on facets of HRQoL. [ABSTRACT FROM AUTHOR]

Cerebral air embolism is a known complication from a myriad of iatrogenic causes. This case describes a 60-year-old female presenting from hemodialysis with altered mental status, bilateral homonymous hemianopia, and repetitive speech. A noncontrast head CT revealed air in the vein of Galen and the deep cerebral veins of the left thalamus and occipital sulcus, a complication from air being introduced into the patient via improper flushing of dialysis tubing. The retrograde flow of air bubbles in the upright patient during dialysis was likely responsible for the air embolus lodging in the cerebral vasculature. This patient was transferred to receive hyperbaric therapy, whereupon the patient survived with residual attention and spatial deficits. [ABSTRACT FROM AUTHOR]

Emotionally salient cues are detected more readily, remembered better, and evoke greater visual cortical responses compared with neutral stimuli. The current study used concurrent EEG-fMRI recordings to identify large-scale network interactions involved in the amplification of visual cortical activity when viewing aversively conditioned cues. To generate a continuous neural signal from pericalcarine visual cortex, we presented rhythmic (10/sec) phase-reversing gratings, the orientation of which predicted the presence (CS+) or absence (CS-) of a cutaneous electric shock (i.e., the unconditioned stimulus). The resulting single trial steady-state visual evoked potential (ssVEP) amplitude was regressed against the wholebrain BOLD signal, resulting in a measure of ssVEP-BOLD coupling. Across all trial types, ssVEP-BOLD coupling was observed in both primary and extended visual cortical regions, the rolandic operculum, as well as the thalamus and bilateral hippo-campus. For CS+ relative to CS- trials during the conditioning phase, BOLD-alone analyses showed CS+ enhancement at the occipital pole, superior temporal sulci, and the anterior insula bilaterally, whereas ssVEP-BOLD coupling was greater in the pericalcarine cortex, inferior parietal cortex, and middle frontal gyrus. Dynamic causal modeling analyses supported connectivity models in which heightened activity in pericalcarine cortex for threat (CS+) arises from cortico-cortical top-down modulation, specifically from the middle frontal gyrus. No evidence was observed for selective pericalcarine modulation by deep cortical structures such as the amygdala or anterior insula, suggesting that the heightened engagement of pericalcarine cortex for threat stimuli ismediated by cortical structures that constitute key nodes of canonical attention networks. [ABSTRACT FROM AUTHOR]

Background: 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. 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. Results: 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 × cm2 across multiple iPSC lines, with a maximum TEER value of 4678 ± 49 Ω × cm2 and fluorescein permeability below 1.95 × 10-7 cm/s. E6-derived BMECs maintained TEER above 1000 Ω × cm2 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 with Parkinson's Disease. Finally, BMECs differentiated using E6 medium responded to inductive cues from astrocytes and pericytes and achieved a maximum TEER value of 6635 ± 315 Ω × cm2, which to our knowledge is the highest reported in vitro TEER value to date. Conclusions: Given the accelerated differentiation, equivalent performance, and reduced cost to produce BMECs, our updated methods should make iPSC-derived in vitro BBB models more accessible for a wide variety of applications. [ABSTRACT FROM AUTHOR]

Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin’s predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours. [ABSTRACT FROM AUTHOR]

Purpose: Quantitative susceptibility mapping (QSM) enables cerebral venous characterization and physiological measurements, such as oxygen extraction fraction (OEF). The exquisite sensitivity of QSM to deoxygenated blood makes it possible to image small veins; however partial volume effects must be addressed for accurate quantification. We present a new method, Iterative Cylindrical Fitting (ICF), to estimate voxel-based partial volume effects for susceptibility maps and use it to improve OEF quantification of small veins with diameters between 1.5 and 4 voxels. Materials and Methods: Simulated QSM maps were generated to assess the performance of the ICF method over a range of vein geometries with varying echo times and noise levels. The ICF method was also applied to in vivo human brain data to assess the feasibility and behavior of OEF measurements compared to the maximum intensity voxel (MIV) method. Results: Improved quantification of OEF measurements was achieved for vessels with contrast to noise greater than 3.0 and vein radii greater than 0.75 voxels. The ICF method produced improved quantitative accuracy of OEF measurement compared to the MIV approach (mean OEF error 7.7 vs. 12.4%). The ICF method provided estimates of vein radius (mean error <27%) and partial volume maps (root mean-squared error <13%). In vivo results demonstrated consistent estimates of OEF along vein segments. Conclusion: OEF quantification in small veins (1.5-4 voxels in diameter) had lower error when using partial volume estimates from the ICF method. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Sotalol and digoxin in fetal atrial flutter: correlation with fetal cardiac output, ejection fraction by planimetrie and middle cerebral artery" by J. C. Otero and colleagues is presented.

The brain is critically dependent on the regulation of blood flow to nourish active neurons. One widely held hypothesis of blood flow regulation holds that active neurons stimulate Ca2+ increases in glial cells, triggering glial release of vasodilating agents. This hypothesis has been challenged, as arteriole dilation can occur in the absence of glial Ca2+ signaling. We address this controversy by imaging glial Ca2+ signaling and vessel dilation in the mouse retina. We find that sensory stimulation results in Ca2+ increases in the glial endfeet contacting capillaries, but not arterioles, and that capillary dilations often follow spontaneous Ca2+ signaling. In IP3R2-/- mice, where glial Ca2+ signaling is reduced, light-evoked capillary, but not arteriole, dilation is abolished. The results show that, independent of arterioles, capillaries actively dilate and regulate blood flow. Furthermore, the results demonstrate that glial Ca2+ signaling regulates capillary but not arteriole blood flow. [ABSTRACT FROM AUTHOR]

The performance of photoacoustic microscopy (PAM) degrades due to the turbidity of the skull that introduces attenuation and distortion of both laser and stimulated ultrasound. In this manuscript, we demonstrated that a newly developed skull optical clearing solution (SOCS) could enhance not only the transmittance of light, but also that of ultrasound in the skull in vitro. Thus the photoacoustic signal was effectively elevated, and the relative strength of the artifacts induced by the skull could be suppressed. Furthermore in vivo studies demonstrated that SOCS could drastically enhance the performance of photoacoustic microscopy for cerebral microvasculature imaging. [ABSTRACT FROM AUTHOR]

As high-resolution functional magnetic resonance imaging (fMRI) and fMRI of cortical layers become more widely used, the question how well high-resolution fMRI signals reflect the underlying neural processing, and how to interpret laminar fMRI data becomes more and more relevant. High-resolution fMRI has shown laminar differences in cerebral blood flow (CBF), volume (CBV), and neurovascular coupling. Features and processes that were previously lumped into a single voxel become spatially distinct at high resolution. These features can be vascular compartments such as veins, arteries, and capillaries, or cortical layers and columns, which can have differences in metabolism. Mesoscopic models of the blood oxygenation level dependent (BOLD) response therefore need to be expanded, for instance, to incorporate laminar differences in the coupling between neural activity, metabolism and the hemodynamic response. Here we discuss biological and methodological factors that affect the modeling and interpretation of high-resolution fMRI data. We also illustrate with examples from neuropharmacology and the negative BOLD response how combining BOLD with CBF- and CBV-based fMRI methods can provide additional information about neurovascular coupling, and can aid modeling and interpretation of high-resolution fMRI. [ABSTRACT FROM AUTHOR]

Background: Functional transcranial Doppler ultrasound (fTCD) is a convenient approach to examine cerebral blood flow velocity (CBFV) in major cerebral arteries. Methods: In this study, the anterior cerebral artery (ACA) was insonated on both sides, that is, right ACA (R-ACA) and left ACA (L-ACA). The envelope signals (the maximum velocity) and the raw signals were analyzed during cognitive processes, i.e. word-generation tasks, geometric tasks and resting state periods separating each task. Data which were collected from 20 healthy participants were used to investigate the changes and the hemispheric functioning while performing cognitive tasks. Signal characteristics were analyzed in time domain, frequency domain and time-frequency domain. Results: Significant results have been obtained through the use of both classic/modern methods (i.e. envelope/raw, time and frequency/information-theoretic and time-frequency domains). The frequency features extracted from the raw signals highlighted sex effects on cerebral blood flow which revealed distinct brain response during each process and during resting periods. In the time-frequency analysis, the distribution of wavelet energies on the envelope signals moved around the low frequencies during mental processes and did not experience any lateralization during cognitive tasks. Conclusions: Even if no lateralization effects were noticed during resting-state, verbal and geometric tasks, understanding CBFV in ACA during cognitive tasks could complement information extracted from cerebral blood flow in middle cerebral arteries during similar cognitive tasks (i.e. sex effects). [ABSTRACT FROM AUTHOR]

The cerebral vasculature provides the massive blood supply that the brain needs to grow and survive. By acquiring distinctive cellular and molecular characteristics it becomes the blood-brain barrier (BBB), a selectively permeable and protective interface between the brain and the peripheral circulation that maintains the extracellular milieu permissive for neuronal activity. Accordingly, there is great interest in uncovering the mechanisms that modulate the formation and differentiation of the brain vasculature. By performing a forward genetic screen in zebrafish we isolated no food for thought (nfty72), a recessive late-lethalmutant that lacksmost of the intracerebral central arteries (CtAs), but not other brain blood vessels. We found that the cerebral vascularization deficit of nft y72 mutants is caused by an inactivating lesion in reversion-inducing cysteine-rich protein with Kazal motifs [reck; also known as suppressor of tumorigenicity 15 protein (ST15)], which encodes a membrane-anchored tumor suppressor glycoprotein. Our findings highlight Reck as a novel and pivotal modulator of the canonical Wnt signaling pathway that acts in endothelial cells to enable intracerebral vascularization and proper expression of molecular markers associated with BBB formation. Additional studies with cultured endothelial cells suggest that, in other contexts, Reck impacts vascular biology via the vascular endothelial growth factor (VEGF) cascade. Together, our findings have broad implications for both vascular and cancer biology. [ABSTRACT FROM AUTHOR]

The hippocampus is one of the earliest and most affected regions in Alzheimer’s disease (AD), followed by the cortex while the cerebellum is largely spared. Importantly, endothelial dysfunction is a common feature of cerebral blood vessels in AD. In this study, we sought to determine if regional heterogeneity of cerebral microvessels might help explain the susceptibility of the hippocampus and cortex as compared to the cerebellum. We isolated microvessels from wild type mice from the cerebellum, cortex, and hippocampus to characterize their vascular phenotype. Superoxide anion was significantly higher in microvessels isolated from the cortex and hippocampus as compared to the cerebellum. Importantly, protein levels of NADPH oxidase (NOX)-2 and NOX-4 were significantly higher in the cortical and hippocampal microvessels as compared to microvessels from the cerebellum. In addition, expression of manganese superoxide dismutase protein was significantly lower in microvessels from the cortex and hippocampus as compared to cerebellum while other antioxidant enzymes were unchanged. There was no difference in eNOS protein expression between the microvessels of the three brain regions; however, bioavailability of tetrahydrobiopterin (BH4), an essential cofactor for eNOS activity, was significantly reduced in microvessels from the hippocampus and cortex as compared to the cerebellum. Higher levels of superoxide and reduced tetrahydrobiopterin bioavailability may help explain the vulnerability of the hippocampus and cortical microvessels to oxidative stress and development of endothelial dysfunction. [ABSTRACT FROM AUTHOR]

The article offers information on a study which suggests the benefits of spontaneous blood pressure (BP) fluctuations to regulate cerebral blood flow (CBF) and cerebral autoregulation (CA). Topics include the relationship between CBF and BP, two indices of dynamic CA (dCA) such as autoregulation index (ARI) and rate of regulation (RoR), and the challenges featured in acquiring accurate dCA measurement.

Postsynaptic density-95 (PSD95) is a scaffolding protein in cerebral vascular smooth muscle cells (cVSMCs), which binds to Shaker-type K+ (KV1) channels and facilitates channel opening through phosphorylation by protein kinase A. β1-Adrenergic receptors (β1ARs) also have a binding motif for PSD95. Functional association of β1AR with KV1 channels through PSD95 may represent a novel vasodilator complex in cerebral arteries (CA). We explored whether a β1AR-PSD95-KV1 complex is a determinant of rat CA dilation. RT-PCR and western blots revealed expression of β1AR in CA. Isoproterenol induced a concentration-dependent dilation of isolated, pressurized rat CA that was blocked by the β1AR blocker CGP20712. Cranial window imaging of middle cerebral arterioles in situ showed isoproterenol- and norepinephrine-induced dilation that was blunted by β1AR blockade. Isoproterenol-induced hyperpolarization of cVSMCs in pressurized CA was blocked by CGP20712. Confocal images of cVSMCs immunostained with antibodies against β1AR and PSD95 indicated strong colocalization, and PSD95 co-immunoprecipitated with β1AR in CA lysate. Blockade of KV1 channels, β1AR or disruption of PSD95-KV1 interaction produced similar blunting of isoproterenol-induced dilation in pressurized CA. These findings suggest that PSD95 mediates a vasodilator complex with β1AR and KV1 channels in cVSMCs. This complex may be critical for proper vasodilation in rat CA. [ABSTRACT FROM AUTHOR]

The (−)- and (+)-clausenamide (CLA) enantiomers have different pharmacokinetic effects in animals, but their association with putative stereoselective regulation of P-glycoprotein (P-gp) remains unclear. Using three cells expressing P-gp—Caco-2, KBv and rat brain microvessel endothelial cells(RBMEC), this study investigated the association of CLA enantiomers with P-gp. The results showed that the rhodamine 123 (Rh123) accumulation, an indicator of P-gp activity, in Caco-2, KBv and RBMECs was increased by (−)CLA (1 or 5 μmol/L) at 8.2%–28.5%, but reduced by (+)CLA at 11.7%–25.9%, showing stereoselectivity in their regulation of P-gp activity. Following co-treatment of these cells with each CLA enantiomer and verapamil as a P-gp inhibitor, the (+)-isomer clearly antagonized the inhibitory effects of verapamil on P-gp efflux, whereas the (−)-isomer had slightly synergistic or additive effects. When higher concentrations (5 or 10 μmol/L) of CLA enantiomers were added, the stimulatory effects of the (+)-isomer were converted into inhibitory ones, leading to an enhanced intracellular uptake of Rh123 by 24.5%–58.2%; but (−)-isomer kept its inhibition to P-gp activity, causing 30.0%–63.0% increase in the Rh123 uptake. The biphasic effects of (+)CLA were confirmed by CLA uptake in the Caco-2 cells. (+)CLA at 1 μmol/L had significantly lower intracellular uptake than (−)CLA with a ratio[(−)/(+)] of 2.593, which was decreased to 2.167 and 1.893 after CLA concentrations increased to 2.5 and 5 μmol/L. Besides, in the non-induced KB cells, (+)CLA(5 μmol/L) upregulated P-gp expression at 54.5% relative to vehicle control, and decreased Rh123 accumulation by 28.2%, while (−)CLA(5 μmol/L) downregulated P-gp expression at 15.9% and increased Rh123 accumulation by 18.0%. These results suggested that (−)CLA could be a P-gp inhibitor and (+)CLA could be a modulator with concentration-dependent biphasic effects on P-gp activity, which may result in drug—drug interactions when combined with other P-gp substrate drugs. [ABSTRACT FROM AUTHOR]

Directional beating of ependymal (E) cells' cilia in the walls of the ventricles in the brain is essential for proper CSF flow. E cells display two forms of planar cell polarity (PCP): rotational polarity of individual cilium and translational polarity (asymmetric positioning of cilia in the apical area). The orientation of individual E cells varies according to their location in the ventricular wall (location-specific PCP). It has been hypothesized that hydrodynamic forces on the apical surface of radial glia cells (RGCs), the embryonic precursors of E cells, could guide location-specific PCP in the ventricular epithelium. However, the detection mechanisms for these hydrodynamic forces have not been identified. Here, we show that the mechanosensory proteins polycystic kidney disease 1 (Pkd1) and Pkd2 are present in primary cilia of RGCs. Ablation of Pkd1 or Pkd2 in Nestin-Cre;Pkd1flox/flox or Nestin-Cre;Pkd2flox/flox mice, affected PCP development in RGCs and E cells. Early shear forces on the ventricular epithelium may activate Pkd1 and Pkd2 in primary cilia of RGCs to properly polarize RGCs and E cells. Consistently, Pkd1, Pkd2, or primary cilia on RGCs were required for the proper asymmetric localization of the PCP protein Vangl2 in E cells' apical area. Analyses of single- and double-heterozygous mutants for Pkd1 and/or Vangl2 suggest that these genes function in the same pathway to establish E cells' PCP. We conclude that Pkd1 and Pkd2 mechanosensory proteins contribute to the development of brain PCP and prevention of hydrocephalus. [ABSTRACT FROM AUTHOR]

In the last decade spatially nonselective arterial spin labeling (SNS-ASL) methods such as velocity-selective ASL (VS-ASL) and acceleration-selective ASL have been introduced, which label spins based on their flow velocity or acceleration rather than spatial localization. Since labeling also occurs within the imaging plane, these methods suffer less from transit delay effects than traditional ASL methods. However, there is a need for validation of these techniques. In this study, a comparison was made between these SNS-ASL techniques with [15O]H2O positron emission tomography (PET), which is regarded as gold standard to measure quantitatively cerebral blood flow (CBF) in humans. In addition, the question of whether these techniques suffered from sensitivity to arterial cerebral blood volume (aCBV), as opposed to producing pure CBF contrast, was investigated. The results show high voxelwise intracranial correlation (0.72 to 0.89) between the spatial distribution of the perfusion signal from the SNS-ASL methods and the PET CBF maps. A similar gray matter (GM) CBF was measured by dual VS-ASL compared with PET (46.7±4.1 versus 47.1±6.5 mL/100 g/min, respectively). Finally, only minor contribution of aCBV patterns in GM to all SNS-ASL methods was found compared with pseudo-continuous ASL. In conclusion, VS-ASL provides a similar quantitative CBF, and all SNS-ASL methods provide qualitatively similar CBF maps as [15O]H2O PET. [ABSTRACT FROM AUTHOR]

Cerebral ischemia results in damage to neuronal circuits and lasting impairment in function. We have previously reported that stimulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors with the ampakine, CX1837, increases brain-derived neurotrophic factor (BDNF) levels and affords significant motor recovery after stroke in young mice. Here, we investigated whether administration of CX1837 in aged (24 months old) mice was equally effective. In a model of focal ischemia, administration of CX1837 from 5 days after stroke resulted in a small gain of motor function by week 6 after stroke. Mice that received a local delivery of BDNF via hydrogel implanted into the stroke cavity also showed a small gain of function from 4 to 6 weeks after stroke. Combining both treatments, however, resulted in a marked improvement in motor function from 2 weeks after insult. Assessment of peri-infarct tissue 2 weeks after stroke revealed a significant increase in p-AKT and p-CREB after the combined drug treatment. Using the pan-AKT inhibitor, GSK-690693, or deletion of CREB from forebrain neurons using the CREB-flox/CAMKii-cre mice, we were able to block the recovery of motor function. These data suggest that combined CX1837 and local delivery of BDNF are required to achieve maximal functional recovery after stroke in aged mice, and is occurring via the AKT-GSK3-CREB signaling pathway. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common form of dementia, affecting more than 35 million people worldwide. Brain hypometabolism is a major feature of AD, appearing decades before cognitive decline and pathologic lesions. To date, the majority of studies on hypometabolism in AD have used transgenic animal models or imaging studies of the human brain. As it is almost impossible to validate these findings using human tissue, alternative models are required. In this study, we show that human stem cell-derived neuron and astrocyte cultures treated with oligomers of amyloid beta 1-42 (Aβ1-42) also display a clear hypometabolism, particularly with regard to utilization of substrates such as glucose, pyruvate, lactate, and glutamate. In addition, a significant increase in the glycogen content of cells was also observed. These changes were accompanied by changes in NAD+/NADH, ATP, and glutathione levels, suggesting a disruption in the energy-redox axis within these cultures. The high energy demands associated with neuronal functions such as memory formation and protection from oxidative stress put these cells at particular risk from Aβ-induced hypometabolism. Further research using this model may elucidate the mechanisms associated with Aβ-induced hypometabolism. [ABSTRACT FROM AUTHOR]

Hemispherectomy is often followed by remarkable recovery of cognitive and motor functions. This reflects plastic capacities of the remaining hemisphere, involving large-scale structural and functional adaptations. Better understanding of these adaptations may (1) provide new insights in the neuronal configuration and rewiring that underlies sensorimotor outcome restoration, and (2) guide development of rehabilitation strategies to enhance recovery after hemispheric lesioning. We assessed brain structure and function in a hemispherectomy model. With MRI we mapped changes in white matter structural integrity and gray matter functional connectivity in eight hemispherectomized rats, compared with 12 controls. Behavioral testing involved sensorimotor performance scoring. Diffusion tensor imaging and resting-state functional magnetic resonance imaging were acquired 7 and 49 days post surgery. Hemispherectomy caused significant sensorimotor deficits that largely recovered within 2 weeks. During the recovery period, fractional anisotropy was maintained and white matter volume and axial diffusivity increased in the contralateral cerebral peduncle, suggestive of preserved or improved white matter integrity despite overall reduced white matter volume. This was accompanied by functional adaptations in the contralateral sensorimotor network. The observed white matter modifications and reorganization of functional network regions may provide handles for rehabilitation strategies improving functional recovery following large lesions. [ABSTRACT FROM AUTHOR]

Locally administered tissue plasminogen activator (TPA) accelerates clearance of intraventricular hemorrhage (IVH), but its impact on neurologic outcomes remains unclear and preclinical research suggests it may have pro-inflammatory effects. We randomly allocated patients with ruptured cerebral aneurysms and IVH, treated with endovascular coiling and ventricular drainage, to receive either 2-mg intraventricular TPA or placebo every 12 hours. Cerebrospinal fluid (CSF) and serum cytokine and white blood cell (WBC) concentrations were measured before drug administration and daily for 72 hours. Cerebrospinal fluid D-dimer levels were assessed 6 and 12 hours after administration to quantify fibrinolysis. Six patients were randomized to each group. Patients treated with TPA developed higher CSF cytokine concentrations compared with placebo-treated patients (P<0.05 for tumor necrosis factor-α, interferon-γ, interleukin (IL)-1α, IL-1β, IL-2, IL-4, and IL-6), as well as higher CSF WBC counts (P=0.03). Differences were greatest after 24 hours and decreased over 48 to 72 hours. The magnitude of the inflammatory response was significantly associated with peak CSF D-dimer concentration and extent of IVH clearance. We conclude that intraventricular TPA administration produces a transient local inflammatory response, the severity of which is strongly associated with the degree of fibrinolysis, suggesting it may be induced by release of hematoma breakdown products, rather than the drug itself. [ABSTRACT FROM AUTHOR]

Increased plasma glucose levels are known to reduce fluorine-18-labeled fluorodeoxyglucose (18F-FDG) uptake in Alzheimer's disease (AD)-related regions, resulting in the appearance of an AD-like pattern. However, the relationships of its appearance with cerebral blood flow and insulin levels are uncertain. We performed 18F-FDG and oxygen-15-labeled water (15O-H2O) positron emission tomography in the fasting and glucose-loading conditions on nine young healthy volunteers with no cognitive impairments. Measurement of plasma glucose and insulin levels confirmed that all subjects were free of insulin resistance, and that glucose loading significantly increased plasma glucose and insulin levels. Fluorine-18-labeled fluorodeoxyglucose and 15O-H2O images were compared between the two conditions, focusing on AD-related regions: precuneus/posterior cingulate (PP), lateral parietal cortex (LPC), and frontal cortex (FC). Volume-of-interest analyses showed significantly lower uptake of both 18F-FDG and 15O-H2O in PP, LPC, and FC after glucose loading (P<0.05). Whole-brain voxel-wise analyses also revealed the PP, LPC, and FC areas where uptake of both 18F-FDG and 15O-H2O decreased (P<0.05, familywise error rate-corrected). We concluded that increased plasma glucose and insulin levels can cause the appearance of the AD-like pattern in both 18F-FDG and 15O-H2O images, and this phenomenon can occur even in subjects without insulin resistance. [ABSTRACT FROM AUTHOR]

The Radiotracer [11C]OMAR was developed for positron emission tomography (PET) imaging of cannabinoid type-1 receptors (CB1R). The objectives of the present study were to evaluate kinetic analysis methods, determine test-retest reliability, and assess gender differences in receptor availability. Dynamic PET data were acquired in 10 human subjects, and analyzed with one-tissue (1T) and two-tissue (2T) compartment models and by the Logan and multilinear analysis (MA1) methods to estimate regional volume of distribution (VT). The 2T model inclusive of a vascular component (2TV) and MA1 were the preferred techniques. Test-retest reliability of VT was good (mean absolute deviation ~9%; intraclass correlation coefficient ~0.7). Tracer parent fraction in plasma was lower in women (P<0.0001). Cerebral uptake normalized by body weight and injected dose was higher in men by 17% (P<0.0001), but VT was significantly greater in women by 23% (P<0.0001). These findings show that [11C]OMAR binding can be reliably quantified by the 2T model or MA1 method and demonstrate the utility of this tracer for in vivo imaging of CB1R. In addition, results from the present study indicate that gender difference in receptor binding should be taken into consideration when [11C]OMAR is used to quantify CB1R availability in neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a psychostimulant that causes neurologic and psychiatric abnormalities. Recent studies have suggested that its neurotoxicity may also result from its ability to compromise the blood-brain barrier (BBB). Herein, we show that METH rapidly increased the vesicular transport across endothelial cells (ECs), followed by an increase of paracellular transport. Moreover, METH triggered the release of tumor necrosis factor-alpha (TNF-α), and the blockade of this cytokine or the inhibition of nuclear factor-kappa B (NF-κB) pathway prevented endothelial dysfunction. Since astrocytes have a crucial role in modulating BBB function, we further showed that conditioned medium obtained from astrocytes previously exposed to METH had a negative impact on barrier properties also via TNF-α/NF-κB pathway. Animal studies corroborated the in vitro results. Overall, we show that METH directly interferes with EC properties or indirectly via astrocytes through the release of TNF-α and subsequent activation of NF-κB pathway culminating in barrier dysfunction. [ABSTRACT FROM AUTHOR]

Dynamic positron emission tomography (PET) data are usually quantified using compartment models (CMs) or derived graphical approaches. Often, however, CMs either do not properly describe the tracer kinetics, or are not identifiable, leading to nonphysiologic estimates of the tracer binding. The PET data are modeled as the convolution of the metabolite-corrected input function and the tracer impulse response function (IRF) in the tissue. Using nonparametric deconvolution methods, it is possible to obtain model-free estimates of the IRF, from which functionals related to tracer volume of distribution and binding may be computed, but this approach has rarely been applied in PET. Here, we apply nonparametric deconvolution using singular value decomposition to simulated and test-retest clinical PET data with four reversible tracers well characterized by CMs ([11C]CUMI-101, [11C]DASB, [11C]PE2I, and [11C]WAY-100635), and systematically compare reproducibility, reliability, and identifiability of various IRF-derived functionals with that of traditional CMs outcomes. Results show that nonparametric deconvolution, completely free of any model assumptions, allows for estimates of tracer volume of distribution and binding that are very close to the estimates obtained with CMs and, in some cases, show better test-retest performance than CMs outcomes. [ABSTRACT FROM AUTHOR]

Traumatic brain injury causes progressive brain atrophy and cognitive decline. Surprisingly, an early treatment with erythropoietin (EPO) prevents these consequences of secondary neurodegeneration, but the mechanisms have remained obscure. Here we show by advanced imaging and innovative analytical tools that recombinant human EPO, a clinically established and neuroprotective growth factor, dampens microglial activity, as visualized also in vivo by a strongly attenuated injury-induced cellular motility. [ABSTRACT FROM AUTHOR]

We present a noninvasive method of photoacoustic tomography (PAT) for imaging cerebral hemodynamics in awake-moving rats. The wearable PAT (wPAT) system has a size of 15 mm in height and 33 mm in diameter, and a weight of ~8 g (excluding cabling). The wPAT achieved an imaging rate of 3.33 frames/s with a lateral resolution of 243 μm. Animal experiments were designed to show wPAT feasibility for imaging cerebral hemodynamics on awake-moving animals. Results showed that the cerebral oxy-hemoglobin and deoxy-hemoglobin changed significantly in response to hyperoxia; and, after the injection of pentylenetetrazol (PTZ), cerebral blood volume changed faster over time and larger in amplitude for rats in awake-moving state compared with rats under anesthesia. By providing a light-weight, high-resolution technology for in vivo monitoring of cerebral hemodynamics in awake-behaving animals, it will be possible to develop a comprehensive understanding on how activity alters hemodynamics in normal and diseased states. [ABSTRACT FROM AUTHOR]

In the bolus tracking technique with computed tomography (CT) or magnetic resonance imaging, cerebral blood flow (CBF) is computed from deconvolution analysis, but its accuracy is unclear. To evaluate the reliability of CT perfusion (CTP)-derived CBF, we examined 27 patients with symptomatic or asymptomatic unilateral cerebrovascular steno-occlusive disease. Results from three deconvolution algorithms, standard singular value decomposition (sSVD), delay-corrected SVD (dSVD), and block-circulant SVD (cSVD), were compared with 15O positron emission tomography (PET) as a reference standard. To investigate CBF errors associated with the deconvolution analysis, differences in lesion-to-normal CBF ratios between PET and CTP were correlated with prolongation of arterial-tissue delay (ATD) and mean transit time (MTT) in the lesion hemisphere. Computed tomography perfusion results strongly depended on the deconvolution algorithms used. Standard singular value decomposition showed ATD-dependent underestimation of CBF ratio, whereas cSVD showed overestimation of the CBF ratio when MTT was severely prolonged in the lesions. The computer simulations reproduced the trend observed in patients. Deconvolution by dSVD can provide lesion-to-normal CBF ratios less dependent on ATD and MTT, but requires accurate ATD maps in advance. A practical and accurate method for CTP is required to assess CBF in patients with MTT-prolonged regions. [ABSTRACT FROM AUTHOR]