scholarly journals Location Matters: Navigating Regional Heterogeneity of the Neurovascular Unit

2021 ◽  
Vol 15 ◽  
Author(s):  
Louis-Philippe Bernier ◽  
Clément Brunner ◽  
Azzurra Cottarelli ◽  
Matilde Balbi

The neurovascular unit (NVU) of the brain is composed of multiple cell types that act synergistically to modify blood flow to locally match the energy demand of neural activity, as well as to maintain the integrity of the blood-brain barrier (BBB). It is becoming increasingly recognized that the functional specialization, as well as the cellular composition of the NVU varies spatially. This heterogeneity is encountered as variations in vascular and perivascular cells along the arteriole-capillary-venule axis, as well as through differences in NVU composition throughout anatomical regions of the brain. Given the wide variations in metabolic demands between brain regions, especially those of gray vs. white matter, the spatial heterogeneity of the NVU is critical to brain function. Here we review recent evidence demonstrating regional specialization of the NVU between brain regions, by focusing on the heterogeneity of its individual cellular components and briefly discussing novel approaches to investigate NVU diversity.

Neuroglia ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 245-281 ◽  
Author(s):  
Alexandr Chvátal ◽  
Alexei Verkhratsky

Neuroscience, like most other divisions of natural philosophy, emerged in the Hellenistic world following the first experimental discoveries of the nerves connecting the brain with the body. The first fundamental doctrine on brain function highlighted the role for a specific substance, pneuma, which appeared as a substrate for brain function and, being transported through the hollow nerves, operated the peripheral organs. A paradigm shift occurred in 17th century when brain function was relocated to the grey matter. Beginning from the end of the 18th century, the existence of active and passive portions of the nervous tissue were postulated. The passive part of the nervous tissue has been further conceptualised by Rudolf Virchow, who introduced the notion of neuroglia as a connective tissue of the brain and the spinal cord. During the second half of the 19th century, the cellular architecture of the brain was been extensively studied, which led to an in-depth morphological characterisation of multiple cell types, including a detailed description of the neuroglia. Here, we present the views and discoveries of the main personalities of early neuroglial research.


2021 ◽  
Vol 22 (11) ◽  
pp. 5818
Author(s):  
Gaylia Jean Harry

A change in microglia structure, signaling, or function is commonly associated with neurodegeneration. This is evident in the patient population, animal models, and targeted in vitro assays. While there is a clear association, it is not evident that microglia serve as an initiator of neurodegeneration. Rather, the dynamics imply a close interaction between the various cell types and structures in the brain that orchestrate the injury and repair responses. Communication between microglia and neurons contributes to the physiological phenotype of microglia maintaining cells in a surveillance state and allows the cells to respond to events occurring in their environment. Interactions between microglia and astrocytes is not as well characterized, nor are interactions with other members of the neurovascular unit; however, given the influence of systemic factors on neuroinflammation and disease progression, such interactions likely represent significant contributes to any neurodegenerative process. In addition, they offer multiple target sites/processes by which environmental exposures could contribute to neurodegenerative disease. Thus, microglia at least play a role as a significant other with an equal partnership; however, claiming a role as an initiator of neurodegeneration remains somewhat controversial.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hironobu Tanigami ◽  
Takayuki Okamoto ◽  
Yuichi Yasue ◽  
Motomu Shimaoka

In the neurovascular units of the central nervous system, astrocytes form extensive networks that physically and functionally connect the neuronal synapses and the cerebral vascular vessels. This astrocytic network is thought to be critically important for coupling neuronal signaling activity and energy demand with cerebral vascular tone and blood flow. To establish and maintain this elaborate network, astrocytes must precisely calibrate their perisynaptic and perivascular processes in order to sense and regulate neuronal and vascular activities, respectively. Integrins, a prominent family of cell-adhesion molecules that support astrocytic migration in the brain during developmental and normal adult stages, have been implicated in regulating the integrity of the blood brain barrier and the tripartite synapse to facilitate the formation of a functionally integrated neurovascular unit. This paper describes the significant roles that integrins and connexins play not only in regulating astrocyte migration during the developmental and adult stages of the neurovascular unit, but also in general health and in such diseases as hepatic encephalopathy.


2021 ◽  
Author(s):  
Mitchell Clough ◽  
Ichen Anderson Chen ◽  
Seong-Wook Park ◽  
Allison M Ahrens ◽  
Jeffrey N Stirman ◽  
...  

Understanding brain function requires monitoring local and global brain dynamics. Two-photon imaging of the brain across mesoscopic scales has presented trade-offs between imaging area and acquisition speed. We describe a flexible cellular resolution two-photon microscope capable of simultaneous video rate acquisition of four independently targetable brain regions spanning an approximate five-millimeter field of view. With this system, we demonstrate the ability to measure calcium activity across mouse sensorimotor cortex at behaviorally relevant timescales.


2021 ◽  
Vol 11 (5) ◽  
pp. 1481-1488
Author(s):  
C. Gunasundari ◽  
K. Selva Bhuvaneswari

Brain tumor is considered to be widely analyzed disease for effective diagnosis and treatment planning. Several approaches were framed to detect and diagnose tumor at early stage. In this work, texture analysis is carried out to analyze the nature of tumor and categorize it. Around 3064 images were analyzed during this study consisting of meningioma, glioma and pituitary tumors. Intensity and gradient pixel based texture analysis is carried out in this analysis. Results confirm that the tumors can be classified and categorized based on the intensity and gradient pixel information. A total of 2216 feature vector is extracted it is observed that the gradient based information aids for better classification of tumors. Localized binary patterns are found to provide detailed information about the subtle variation in the brain regions due to the presence of abnormality in brain tissues. It is further observed that the normalized feature vectors show better differentiation between tumor categories. The ROC and PRC curves exhibit the high classification ability using the extracted features to differentiate tumor grades.


1987 ◽  
Vol 252 (6) ◽  
pp. H1183-H1191
Author(s):  
C. Iadecola ◽  
P. M. Lacombe ◽  
M. D. Underwood ◽  
T. Ishitsuka ◽  
D. J. Reis

We studied whether adrenal medullary catecholamines (CAs) contribute to the metabolically linked increase in regional cerebral blood flow (rCBF) elicited by electrical stimulation of the dorsal medullary reticular formation (DMRF). Rats were anesthetized (alpha-chloralose, 30 mg/kg), paralyzed, and artificially ventilated. The DMRF was electrically stimulated with intermittent trains of pulses through microelectrodes stereotaxically implanted. Blood gases were controlled and, during stimulation, arterial pressure was maintained within the autoregulated range for rCBF. rCBF and blood-brain barrier (BBB) permeability were determined in homogenates of brain regions by using [14C]iodoantipyrine and alpha-aminoisobutyric acid (AIB), respectively, as tracers. Plasma CAs (epinephrine and norepinephrine) were measured radioenzymatically. DMRF stimulation increased rCBF throughout the brain (n = 5; P less than 0.01, analysis of variance) and elevated plasma CAs substantially (n = 4). Acute bilateral adrenalectomy abolished the increase in plasma epinephrine (n = 4), reduced the increases in flow (n = 6) in cerebral cortex (P less than 0.05), and abolished them elsewhere in brain (P greater than 0.05). Comparable effects on rCBF were obtained by selective adrenal demedullation (n = 7) or pretreatment with propranolol (1.5 mg/kg iv) (n = 5). DMRF stimulation did not increase the permeability of the BBB to AIB (n = 5). We conclude that the increases in rCBF elicited from the DMRF has two components, one dependent on, and the other independent of CAs. Since the BBB is impermeable to CAs and DMRF stimulation fails to open the BBB, the results suggest that DMRF stimulation allows, through a mechanism not yet determined, circulating CAs to act on brain and affect brain function.


2020 ◽  
Vol 49 (D1) ◽  
pp. D1029-D1037
Author(s):  
Liting Song ◽  
Shaojun Pan ◽  
Zichao Zhang ◽  
Longhao Jia ◽  
Wei-Hua Chen ◽  
...  

Abstract The human brain is the most complex organ consisting of billions of neuronal and non-neuronal cells that are organized into distinct anatomical and functional regions. Elucidating the cellular and transcriptome architecture underlying the brain is crucial for understanding brain functions and brain disorders. Thanks to the single-cell RNA sequencing technologies, it is becoming possible to dissect the cellular compositions of the brain. Although great effort has been made to explore the transcriptome architecture of the human brain, a comprehensive database with dynamic cellular compositions and molecular characteristics of the human brain during the lifespan is still not available. Here, we present STAB (a Spatio-Temporal cell Atlas of the human Brain), a database consists of single-cell transcriptomes across multiple brain regions and developmental periods. Right now, STAB contains single-cell gene expression profiling of 42 cell subtypes across 20 brain regions and 11 developmental periods. With STAB, the landscape of cell types and their regional heterogeneity and temporal dynamics across the human brain can be clearly seen, which can help to understand both the development of the normal human brain and the etiology of neuropsychiatric disorders. STAB is available at http://stab.comp-sysbio.org.


2003 ◽  
Vol 83 (4) ◽  
pp. 1183-1221 ◽  
Author(s):  
MITCHELL CHESLER

Chesler, Mitchell. Regulation and Modulation of pH in the Brain. Physiol Rev 83: 1183-1221, 2003; 10.1152/physrev.00010.2003.—The regulation of pH is a vital homeostatic function shared by all tissues. Mechanisms that govern H+ in the intracellular and extracellular fluid are especially important in the brain, because electrical activity can elicit rapid pH changes in both compartments. These acid-base transients may in turn influence neural activity by affecting a variety of ion channels. The mechanisms responsible for the regulation of intracellular pH in brain are similar to those of other tissues and are comprised principally of forms of Na+/H+ exchange, Na+-driven Cl-/HCO3- exchange, Na+-HCO3- cotransport, and passive Cl-/HCO3- exchange. Differences in the expression or efficacy of these mechanisms have been noted among the functionally and morphologically diverse neurons and glial cells that have been studied. Molecular identification of transporter isoforms has revealed heterogeneity among brain regions and cell types. Neural activity gives rise to an assortment of extracellular and intracellular pH shifts that originate from a variety of mechanisms. Intracellular pH shifts in neurons and glia have been linked to Ca2+ transport, activation of acid extrusion systems, and the accumulation of metabolic products. Extracellular pH shifts can occur within milliseconds of neural activity, arise from an assortment of mechanisms, and are governed by the activity of extracellular carbonic anhydrase. The functional significance of these compartmental, activity-dependent pH shifts is discussed.


1989 ◽  
Vol 121 (2) ◽  
pp. 331-335 ◽  
Author(s):  
M. C. Ruiz de Elvira ◽  
A. K. Sinha ◽  
M. Pickard ◽  
M. Ballabio ◽  
M. Hubank ◽  
...  

ABSTRACT Calmodulin-regulated phosphatase activity was measured in the brain of 2-month-old rats born from hypothyroid and normal dams, using a fluorometric enzyme assay developed for this purpose. Calmodulin content was measured in the same brain regions by radioimmunoassay. Significant differences between groups in weight and protein content, basal phosphatase and calmodulin-regulated phosphatase activity were found. The brain region most affected was the cerebellum, where basal and calmodulin-regulated phosphatase activities, and protein content were increased. The data point towards a lasting effect of maternal hypothyroxinaemia on the brain function of the progeny. Journal of Endocrinology (1989) 121, 331–335


2020 ◽  
Author(s):  
Doris Voina ◽  
Stefano Recanatesi ◽  
Brian Hu ◽  
Eric Shea-Brown ◽  
Stefan Mihalas

AbstractAs animals adapt to their environments, their brains are tasked with processing stimuli in different sensory contexts. Whether these computations are context dependent or independent, they are all implemented in the same neural tissue. A crucial question is what neural architectures can respond flexibly to a range of stimulus conditions and switch between them. This is a particular case of flexible architecture that permits multiple related computations within a single circuit.Here, we address this question in the specific case of the visual system circuitry, focusing on context integration, defined as the integration of feedforward and surround information across visual space. We show that a biologically inspired microcircuit with multiple inhibitory cell types can switch between visual processing of the static context and the moving context. In our model, the VIP population acts as the switch and modulates the visual circuit through a disinhibitory motif. Moreover, the VIP population is efficient, requiring only a relatively small number of neurons to switch contexts. This circuit eliminates noise in videos by using appropriate lateral connections for contextual spatio-temporal surround modulation, having superior denoising performance compared to circuits where only one context is learned. Our findings shed light on a minimally complex architecture that is capable of switching between two naturalistic contexts using few switching units.Author SummaryThe brain processes information at all times and much of that information is context-dependent. The visual system presents an important example: processing is ongoing, but the context changes dramatically when an animal is still vs. running. How is context-dependent information processing achieved? We take inspiration from recent neurophysiology studies on the role of distinct cell types in primary visual cortex (V1).We find that relatively few “switching units” — akin to the VIP neuron type in V1 in that they turn on and off in the running vs. still context and have connections to and from the main population — is sufficient to drive context dependent image processing. We demonstrate this in a model of feature integration, and in a test of image denoising. The underlying circuit architecture illustrates a concrete computational role for the multiple cell types under increasing study across the brain, and may inspire more flexible neurally inspired computing architectures.


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