scholarly journals Automated diffusion-based parcellation of the hypothalamus reveals subunit-specific associations with obesity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Melanie Spindler ◽  
Jale Özyurt ◽  
Christiane M. Thiel
Keyword(s):  
Food Intake ◽  
Ex Vivo ◽  
Functional Anatomy ◽  
Mean Diffusivity ◽  
Structural Mri ◽  
Clustering Methods ◽  
Endocrine Activity ◽  
Human Connectome Project ◽  
Using Data

AbstractThe hypothalamus is a small, yet highly versatile structure mainly involved in bodily functions such as control of food intake and endocrine activity. Functional anatomy of different hypothalamic areas is mainly investigated using structural MRI, validated by ex-vivo histological studies. Based on diffusion-weighted imaging (DWI), recent automated clustering methods provide robust tools for parcellation. Using data of 100 healthy adults provided by the Human Connectome Project Database, we applied DWI-based automated clustering to the hypothalamus and related microstructural properties in these hypothalamic compartments to obesity. Our results suggest that the hypothalamus can be reliably partitioned into four clusters in each hemisphere using diffusion-based parcellation. These correspond to an anterior–superior, anterior-inferior, intermediate, and posterior cluster. Obesity was predicted by mean diffusivity of the anterior–superior cluster, suggesting altered inhibition of food intake. The proposed method provides an automated hypothalamic parcellation technique based on DWI data to explore anatomy and function of hypothalamic subunits in vivo in humans.

scholarly journals Pannexin 1 Channels Control the Hemodynamic Response to Hypoxia by Regulating O2-Sensitive Extracellular ATP in Blood

2021 ◽  
Author(s):  
Brett S. Kirby ◽  
Matthew A. Sparks ◽  
Eduardo R. Lazarowski ◽  
Denise A Lopez Domowicz ◽  
Hongmei Zhu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Extracellular Atp ◽  
Metabolic Demand ◽  
Flow Transducer ◽  
Mechanically Ventilated ◽  
Pannexin 1 ◽  
Hypoxic Vasodilation ◽  
Using Data ◽  
Artery Flow

Pannexin1 (Panx1) channels export ATP and may contribute to increased concentration of the vasodilator ATP in plasma during hypoxia in vivo. We hypothesized that Panx1 channels and associated ATP export contributes to hypoxic vasodilation, a mechanism that facilitates the matching of oxygen delivery to tissue metabolic demand. Male and female mice devoid of Panx1 (Panx1-/-) and wild-type controls (WT) were anesthetized, mechanically ventilated, and instrumented with a carotid artery catheter or femoral artery flow transducer for hemodynamic and plasma ATP monitoring during inhalation of 21% (normoxia) or 10% oxygen (hypoxia). ATP export from WT vs. Panx1-/- erythrocytes (RBC) was determined ex vivo via tonometer experimentation across progressive deoxygenation. Mean arterial pressure (MAP) was similar in Panx1-/- (N=6) and WT (N=6) mice in normoxia, but the decrease in MAP in hypoxia seen in WT was attenuated in Panx1-/- mice (-16±9% vs -2±8%; P<0.05). Hindlimb blood flow (HBF) was significantly lower in Panx1-/- (N=6) vs. WT (N=6) basally, and increased in WT but not Panx1-/- mice during hypoxia (8±6% vs -10±13%; P<0.05). Estimation of hindlimb vascular conductance using data from the MAP and HBF experiments showed an average response of 28% for WT vs -9% for Panx1-/- mice. Mean venous plasma ATP during hypoxia was 57% lower in Panx1-/- (N=6) vs WT mice (N=6) (P<0.05). Mean hypoxia-induced ATP export from RBCs from Panx1-/- mice (N=8) was 82% lower than from WT (N=8) ( P<0.05). Panx1 channels participate in hemodynamic responses consistent with hypoxic vasodilation by regulating hypoxia-sensitive extracellular ATP levels in blood.

scholarly journals Astrocytes in the dorsal vagal complex are not activated by systemic glucoprivation and their chemogenetic activation does not elicit homeostatic glucoregulatory responses in mice

2021 ◽  
Author(s):  
Alastair J MacDonald ◽  
Katherine R Pye ◽  
Craig Beall ◽  
Kate LJ Ellacott
Keyword(s):  
Blood Glucose ◽  
Food Intake ◽  
Ex Vivo ◽  
Glucose Deprivation ◽  
Active Role ◽  
Glucose Absorption ◽  
Dorsal Vagal Complex ◽  
Gfap Immunoreactivity ◽  
Regulate Food Intake

The dorsal vagal complex (DVC) is a brainstem site regulating diverse aspects of physiology including food intake and blood glucose homeostasis. Astrocytes are purported to play an active role in regulating DVC function and, by extension, physiological parameters. Previous work has demonstrated that DVC astrocytes directly sense hormones that regulate food intake and blood glucose and are critical for their effect. In addition, DVC astrocytes in ex vivo slices respond to low tissue glucose. The response of neurons, including catecholaminergic neurons, to low glucose is conditional on intact astrocyte signalling in slice preparations suggesting astrocytes are possibly the primary sensors of glucose deprivation (glucoprivation). Based on these findings we hypothesised that if DVC astrocytes act as glucoprivation sensors in vivo they would both show a response to systemic glucoprivation and drive physiological responses to restore blood glucose. We found that 2 hours of systemic glucoprivation induced neither FOS nor glial fibrillary acidic protein (GFAP)-immunoreactivity in DVC astrocytes, specifically those in the nucleus of the solitary tract (NTS). Furthermore, we found that while chemogenetic activation of DVC astrocytes suppressed food intake by reducing both meal size and meal number, this manipulation also suppressed food intake under conditions of glucoprivation. Chemogenetic activation of DVC astrocytes did not increase basal blood glucose nor protect against insulin-induced hypoglycaemia. In male mice chemogenetic DVC astrocyte activation did not alter glucose tolerance, in female mice the initial glucose excursion was reduced, suggesting enhanced glucose absorption. Taken together this suggests that as a whole-population DVC astrocytes do not function as glucoprivation sensors in vivo in mice. Instead, we propose that DVC astrocytes play an indispensable, homeostatic role to maintain the function of glucoregulatory neuronal circuitry.

scholarly journals Diffusion kurtosis imaging of gray matter in young adults with autism spectrum disorder

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Faye McKenna ◽  
Laura Miles ◽  
Jeffrey Donaldson ◽  
F. Xavier Castellanos ◽  
Mariana Lazar
Keyword(s):  
Autism Spectrum Disorder ◽  
Young Adults ◽  
Gray Matter ◽  
Ex Vivo ◽  
Mean Diffusivity ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Diffusion Kurtosis Imaging ◽  
Adults With Autism

AbstractPrior ex vivo histological postmortem studies of autism spectrum disorder (ASD) have shown gray matter microstructural abnormalities, however, in vivo examination of gray matter microstructure in ASD has remained scarce due to the relative lack of non-invasive methods to assess it. The aim of this work was to evaluate the feasibility of employing diffusional kurtosis imaging (DKI) to describe gray matter abnormalities in ASD in vivo. DKI data were examined for 16 male participants with a diagnosis of ASD and IQ>80 and 17 age- and IQ-matched male typically developing (TD) young adults 18–25 years old. Mean (MK), axial (AK), radial (RK) kurtosis and mean diffusivity (MD) metrics were calculated for lobar and sub-lobar regions of interest. Significantly decreased MK, RK, and MD were found in ASD compared to TD participants in the frontal and temporal lobes and several sub-lobar regions previously associated with ASD pathology. In ASD participants, decreased kurtosis in gray matter ROIs correlated with increased repetitive and restricted behaviors and poor social interaction symptoms. Decreased kurtosis in ASD may reflect a pathology associated with a less restrictive microstructural environment such as decreased neuronal density and size, atypically sized cortical columns, or limited dendritic arborizations.

scholarly journals In vivo high-resolution structural MRI-based atlas of human thalamic nuclei

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Manojkumar Saranathan ◽  
Charles Iglehart ◽  
Martin Monti ◽  
Thomas Tourdias ◽  
Brian Rutt
Keyword(s):  
Multiple Sclerosis ◽  
Essential Tremor ◽  
Healthy Subjects ◽  
Neurological Diseases ◽  
Structural Mri ◽  
Thalamic Nuclei ◽  
Conventional Mri ◽  
Mri Scans ◽  
Using Data

AbstractThalamic nuclei play critical roles in regulation of neurological functions like sleep and wakefulness. They are increasingly implicated in neurodegenerative and neurological diseases such as multiple sclerosis and essential tremor. However, segmentation of thalamic nuclei is difficult due to their poor visibility in conventional MRI scans. Sophisticated methods have been proposed which require specialized MRI acquisitions and complex post processing. There are few high spatial resolution (1 mm3 or higher) in vivo MRI thalamic atlases available currently. The goal of this work is the development of an in vivo MRI-based structural thalamic atlas at 0.7 × 0.7 × 0.5 mm resolution based on manual segmentation of 9 healthy subjects using the Morel atlas as a guide. Using data analysis from healthy subjects as well as patients with multiple-sclerosis and essential tremor and at 3T and 7T MRI, we demonstrate the utility of this atlas to provide fast and accurate segmentation of thalamic nuclei when only conventional T1 weighted images are available.

Lesion growth and degeneration patterns measured using diffusion tensor 9.4-T magnetic resonance imaging in rat spinal cord injury

2010 ◽  
Vol 13 (2) ◽  
pp. 181-192 ◽  
Author(s):  
Benjamin M. Ellingson ◽  
Brian D. Schmit ◽  
Shekar N. Kurpad
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mr Imaging ◽  
Diffusion Tensor ◽  
Ex Vivo ◽  
Mean Diffusivity ◽  
Cavity Formation ◽  
Cord Injury ◽  
Lesion Growth

Object Using diffusion tensor MR imaging, the authors conducted a study to explore lesion growth and degeneration patterns, from the acute through chronic stages of spinal cord injury (SCI), in an experimental animal model. Methods In vivo and ex vivo diffusion tensor imaging was performed using a 9.4-T MR imaging system in rats allowed to recover from traumatic contusion SCI from 2 weeks through 25 weeks postinjury, mimicking progression of human SCI from the acute through chronic stages. Results Results showed significant growth of the traumatic lesion up to 15 weeks postinjury, where both the size and mean diffusivity (MD) reached a maximum that was maintained through the remainder of recovery. Mean diffusivity was sensitive to overall spinal cord integrity, whereas fractional anisotropy showed specificity to sites of cavity formation. The use of an MD contour map for in vivo data and a 3D surface map for ex vivo data, showing MD as a function of rostral-caudal distance and recovery time, allowed documentation of rostral and caudal spreading of the lesion. Conclusions Results from this study demonstrate changes in both lesion morphology and diffusivity beyond previously reported time points and provide a unique perspective on the process of cavity formation and degeneration following traumatic SCI. Additionally, results suggest that MD more accurately defines regions of histological damage than do regions of T2 signal hyperintensity. This could have significant clinical implications in the detection and potential treatment of posttraumatic syringes in SCI.

scholarly journals 3D Whole-Brain Imaging Approaches to Study Brain Tumors

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1897
Author(s):  
Julian Taranda ◽  
Sevin Turcan
Keyword(s):  
Brain Tumors ◽  
Ex Vivo ◽  
Tumor Biology ◽  
Three Dimensional ◽  
Light Sheet ◽  
Response To Therapy ◽  
Imaging Modalities ◽  
Two Photon ◽  
Using Data

Although our understanding of the two-dimensional state of brain tumors has greatly expanded, relatively little is known about their spatial structures. The interactions between tumor cells and the tumor microenvironment (TME) occur in a three-dimensional (3D) space. This volumetric distribution is important for elucidating tumor biology and predicting and monitoring response to therapy. While static 2D imaging modalities have been critical to our understanding of these tumors, studies using 3D imaging modalities are needed to understand how malignant cells co-opt the host brain. Here we summarize the preclinical utility of in vivo imaging using two-photon microscopy in brain tumors and present ex vivo approaches (light-sheet fluorescence microscopy and serial two-photon tomography) and highlight their current and potential utility in neuro-oncology using data from solid tumors or pathological brain as examples.

scholarly journals Comparison of In Vivo and Ex Vivo Magnetic Resonance Imaging in a Rat Model for Glioblastoma-Associated Epilepsy

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1311
Author(s):  
Charlotte Bouckaert ◽  
Emma Christiaen ◽  
Jeroen Verhoeven ◽  
Benedicte Descamps ◽  
Valerie De Meulenaere ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Ex Vivo ◽  
Mean Diffusivity ◽  
Common Symptom ◽  
Peritumoral Edema ◽  
Resonance Imaging ◽  
Tumor Mass ◽  
Preclinical Treatment

Magnetic resonance imaging (MRI) is frequently used for preclinical treatment monitoring in glioblastoma (GB). Discriminating between tumors and tumor-associated changes is challenging on in vivo MRI. In this study, we compared in vivo MRI scans with ex vivo MRI and histology to estimate more precisely the abnormal mass on in vivo MRI. Epileptic seizures are a common symptom in GB. Therefore, we used a recently developed GB-associated epilepsy model from our group with the aim of further characterizing the model and making it useful for dedicated epilepsy research. Ten days after GB inoculation in rat entorhinal cortices, in vivo MRI (T2w and mean diffusivity (MD)), ex vivo MRI (T2w) and histology were performed, and tumor volumes were determined on the different modalities. The estimated abnormal mass on ex vivo T2w images was significantly smaller compared to in vivo T2w images, but was more comparable to histological tumor volumes, and might be used to estimate end-stage tumor volumes. In vivo MD images displayed tumors as an outer rim of hyperintense signal with a core of hypointense signal, probably reflecting peritumoral edema and tumor mass, respectively, and might be used in the future to distinguish the tumor mass from peritumoral edema—associated with reactive astrocytes and activated microglia, as indicated by an increased expression of immunohistochemical markers—in preclinical models. In conclusion, this study shows that combining imaging techniques using different structural scales can improve our understanding of the pathophysiology in GB.

scholarly journals In vivo structural MRI-based atlas of human thalamic nuclei

2020 ◽  
Author(s):  
Manojkumar Saranathan ◽  
Charles Iglehart ◽  
Martin Monti ◽  
Thomas Tourdias ◽  
Brian K Rutt
Keyword(s):  
Multiple Sclerosis ◽  
Essential Tremor ◽  
Healthy Subjects ◽  
Neurological Diseases ◽  
Structural Mri ◽  
Thalamic Nuclei ◽  
Conventional Mri ◽  
Mri Scans ◽  
Using Data

Thalamic nuclei play critical roles in regulation of neurological functions like sleep and wakefulness. They are increasingly implicated in neurodegenerative and neurological diseases such as multiple sclerosis and essential tremor. However, segmentation of thalamic nuclei is difficult due to their poor visibility in conventional MRI scans. Sophisticated methods have been proposed which require specialized MRI acquisitions and complex post processing. There are very few digital MRI thalamic atlases and they have been constructed using a small number of post-mortem brains. The goal of this work is the development of a structural thalamic atlas at high spatial resolution based on manual segmentation of 20 subjects that include healthy subjects and patients with multiple-sclerosis. Using data analysis from healthy subjects as well as patients with multiple-sclerosis and essential tremor and at 3T and 7T MRI, we demonstrate the utility of this atlas to provide fast and accurate segmentation of thalamic nuclei when only conventional T1 weighted images are available.

scholarly journals Linking immune-mediated damage to neurodegeneration in multiple sclerosis: could network-based MRI help?

2021 ◽  
Author(s):  
Sergiu Groppa ◽  
Gabriel Gonzalez-Escamilla ◽  
Arman Eshaghi ◽  
Sven G Meuth ◽  
Olga Ciccarelli
Keyword(s):  
Multiple Sclerosis ◽  
Grey Matter ◽  
Dynamic Models ◽  
Ex Vivo ◽  
Unmet Need ◽  
Neuronal Loss ◽  
Structural Mri ◽  
Conceptual Shift ◽  
Brain Reorganization

Abstract Inflammatory demyelination characterizes the initial stages of multiple sclerosis, while progressive axonal and neuronal loss are coexisting and significantly contribute to the long-term physical and cognitive impairment. There is an unmet need for a conceptual shift from a dualistic view of multiple sclerosis pathology, involving either inflammatory demyelination or neurodegeneration, to integrative dynamic models of brain reorganization, where, glia-neuron interactions, synaptic alterations, and grey matter pathology are longitudinally envisaged at the whole-brain level. Functional and structural MRI can delineate network hallmarks for relapses, remissions or disease progression, which can be linked to the pathophysiology behind inflammatory attacks, repair, and neurodegeneration. Here, we aim to unify recent findings of grey matter circuits dynamics in multiple sclerosis within the framework of molecular and pathophysiological hallmarks combined with disease-related network reorganization, while highlighting advances from animal models (in vivo and ex vivo) and human clinical data (imaging and histological). We propose that MRI-based brain networks characterization is essential for better delineating ongoing pathology and elaboration of particular mechanisms that may serve for accurate modelling and prediction of disease courses throughout disease stages.

scholarly journals Role of Neuronal Energy Status in the Regulation of Adenosine 5′-Monophosphate-Activated Protein Kinase, Orexigenic Neuropeptides Expression, and Feeding Behavior

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Kichoon Lee ◽  
Bing Li ◽  
Xiaochun Xi ◽  
Yeunsu Suh ◽  
Roy J. Martin
Keyword(s):  
Protein Kinase ◽  
Food Intake ◽  
Feeding Behavior ◽  
High Glucose ◽  
Ex Vivo ◽  
Nutrient Sensing ◽  
Central Administration ◽  
Energy Status ◽  
Low Glucose

Nutrient sensing in the hypothalamus is tightly related to food intake regulation. However, the mechanisms by which the nutrient-sensing cells of the brain translate this signal of energy need into feeding behavior via regulation of neuropeptide expression are not known. To address this issue, we investigated two neuronal cell lines expressing agouti-related protein (AgRP), ex vivo hypothalamic tissues, and in vivo whole animals. Maintaining cells in a low cellular ATP concentration generated by low glucose, 2-deoxyglucose (2-DG), ATP synthesis inhibitor, and 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside increased phosphorylation of AMP-activated protein kinase (AMPK) and increased AgRP expression, whereas maintaining cells in high ATP status by high glucose and pyruvate supplementation in 2-DG-treated cells decreased phosphorylation of AMPK and decreased AgRP expression. Overexpression of a dominant-inhibitory mutant of AMPK significantly decreased low-glucose- or 2-DG-induced AgRP expression. Furthermore, ex vivo hypothalamus culture in high glucose concentrations decreased both expression and phosphorylation of AMPK and expression of both AgRP and neuropeptide Y, whereas pyruvate supplementation suppressed a 2-DG-induced AgRP expression. Finally, our in vivo studies clearly show that central administration of pyruvate dramatically delayed 2-DG-induced food intake. These data indicate that modulation of ATP levels in neuronal cells triggers a cascade of events via AMPK that modulate feeding behavior to restore energy status of cells.

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