Neurovascular unit

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The neurovascular unit (NVU) comprises the components of the brain that collectively regulate cerebral blood flow in order to deliver the requisite nutrients to activated neurons. [1] The NVU addresses the brain's unique dilemma of having high energy demands yet low energy storage capacity. In order to function properly, the brain must receive substrates for energy metabolism–mainly glucose–in specific areas, quantities, and times. [2] Neurons do not have the same ability as, for example, muscle cells, which can use up their energy reserves and refill them later; therefore, cerebral metabolism must be driven in the moment. The neurovascular unit facilitates this ad hoc delivery and, thus, ensures that neuronal activity can continue seamlessly. [2]

Contents

The neurovascular unit was formalized as a concept in 2001, at the inaugural Stroke Progress Review Group of the National Institute of Neurological Disorders and Stroke (NINDS). [1] In prior years, the importance of both neurons and cerebral vasculature was well known; however, their interconnected relationship was not. The two were long considered distinct entities which, for the most part, operated independently. Since 2001, though, the rapid increase of scientific papers citing the neurovascular unit represents the growing understanding of the interactions that occur between the brain’s cells and blood vessels. [1]

The neurovascular unit consists of neurons, astrocytes, vasculature (endothelial and vascular mural cells), the vasomotor apparatus (smooth muscle cells and pericytes), and microglia. [1] Together these function in the homeostatic haemodynamic response of cerebral hyperaemia. [3] Cerebral hyperaemia is a fundamental central nervous system mechanism of homeostasis that increases blood supply to neural tissue when necessary. [3] This mechanism controls oxygen and nutrient levels using vasodilation and vasoconstriction in a multidimensional process involving the many cells of the neurovascular unit, along with multiple signaling molecules. [1] The interactions between the components of the NVU allow it to sense neurons' needs of oxygen and glucose and, in turn, trigger the appropriate vasodilatory or vasoconstrictive responses. [3] Thus, the NVU provides the architecture behind neurovascular coupling, which connects neuronal activity to cerebral blood flow and highlights the interdependence of their development, structure, and function. [1]

A schematic of the neurovascular unit (NVU), where astrocyte processes surround the capillary basement membrane and pericytes, creating the glia limitans. Also, resident in the perivascular space are antigen-presenting cells (APCs) and border-associated macrophages (BAMs). Neurovascular unit.jpg
A schematic of the neurovascular unit (NVU), where astrocyte processes surround the capillary basement membrane and pericytes, creating the glia limitans. Also, resident in the perivascular space are antigen-presenting cells (APCs) and border-associated macrophages (BAMs).

The temporal and spatial link between cerebral blood flow and neuronal activity allows the former to serve as a proxy for the latter. Neuroimaging techniques that directly or indirectly monitor blood flow, such as fMRI and PET scans, can, thus, measure and locate activity in the brain with precision. [1] Imaging of the brain also allows researchers to better understand the neurovascular unit and its many complexities. Furthermore, any impediments to the function of the neurovascular system will prevent neurons from receiving the appropriate nutrients. A complete stoppage for only a few minutes, which could be caused by arterial occlusion or heart failure, can result in permanent damage and death. Dysfunction in the NVU is also associated with neurodegenerative diseases including Alzheimer's and Huntington's disease. [1]

Function

Anatomical components

The neurovascular unit is made up of vascular cells (including endothelium, pericytes, and smooth muscle cells), glia (astrocytes and microglia), and neurons with synaptic junctions for signaling. [1] Cerebral vessels, namely arterioles and the perivascular compartment, form the network of the NVU. [4] Arterioles are made up of pial vessels and arterioles, and the perivascular compartment includes perivascular macrophages in addition to Mato, pial, and mast cells. Cerebral blood flow is a critical component of this overall system and it is facilitated by the neck arteries. Segmented vascular resistance, or the amount of flow control that each section of the brain maintains, is measured as the ratio of the blood pressure gradient to blood flow volume. [5] The blood flow within the NVU is a low resistance channel that allows blood to be distributed to different parts of the body. [6] The cells of the NVU sense the needs of neural tissue and release many different mediators that engage in signaling pathways and initiate effector systems such as the myogenic effect; these mediators trigger the vascular smooth muscle cells to increase blood flow through vasodilation or to reduce blood flow by vasoconstriction. [3] [1] This is recognized as a multidimensional response that operates across the cerebrovascular network as a whole. [1]

Blood–brain barrier

The cells of the neurovascular unit also make up the blood–brain barrier (BBB), which plays an important role in maintaining the microenvironment of the brain. [7] In addition to regulating the exit and entrance of blood, the blood–brain barrier also filters toxins that may cause inflammation, injury, and disease. [8] The overall microvasculature unit functions as a defense for the central nervous system. [7] Encompassed within the BBB are two types of blood vessels: endothelial and mural cells. Endothelial cells form the wall of the BBB, while mural cells exist on the outer surface of this layer of endothelial cells. The mural cells also have their own abluminal layer which hosts pericytes that work to maintain the permeability of the barrier, and the epithelial cells filter the amount of toxins entering. These cells connect to different segments of the vascular tree that exist within the brain. [8]

Neurovascular coupling

Cellular processes critically rely on the production of adenosine triphosphate (ATP), which requires glucose and oxygen. [9] These need to be delivered to areas in the brain with consistency via cerebral blood flow. In order for the brain to receive enough blood flow when in high demand, coupling occurs between neurons and CBF. Neurovascular coupling encompasses the changes in cerebral blood flow that occur in response to the level of neuronal activity. [1] When the brain needs to exert more energy, there is an associated increase in the level of blood flow to compensate for this. The brain does not have a place where it stores energy, and, therefore, the response of blood flow has to be immediate so that crucial functions for continued life can persist. Difficulties arise when angiotensin proteins are present in higher concentrations, as there is an associated increase in blood flow that leads to hypertension and potential disorders. [5] Furthermore, modern imaging techniques have allowed researchers to view and study cerebral blood flow in a noninvasive manner. Ultimately, neurovascular coupling promotes brain health by moderating proper cerebral blood flow. There is still much more to be discovered about it, though; and, due to the difficulty of in vivo research, the growing body of knowledge on neurovascular coupling relies heavily on ex vivo techniques for imaging the neurovascular unit.

Imaging

The neurovascular unit enables imaging techniques to measure neuronal activity by tracking blood flow. Various other types of neuroimaging also allow the NVU itself to be studied by providing visual insights into the complex interactions between neurons, glial cells, and blood vessels in the brain.

Fluorescence microscopy

Fluorescence microscopy is a widely used imaging technique that utilizes fluorescent probes to visualize specific molecules or structures within the neurovascular unit. [10] It allows researchers to label and track cellular components, such as neurons, astrocytes, and blood vessel markers, with high specificity. [11] Fluorescence imaging offers excellent spatial resolution, allowing for detailed visualization of cellular morphology and localized molecular interactions. [12] By using different fluorophores, researchers can simultaneously examine multiple cellular components and molecular pathways of the neurovascular unit. However, limited tissue penetration depth, photobleaching, and phototoxicity negatively impact the potential for long-term imaging studies. [12]

Electron microscopy

Electron microscopy provides details of the neurovascular unit at the nanometer scale by using a focused beam of electrons instead of light, enabling higher resolution imaging. Transmission electron microscopy images thin tissue sections, providing detailed information about the fine cellular structures, including synapses and organelles. [13] Scanning electron microscopy, on the other hand, provides 3D information by scanning a focused electron beam across the sample's surface, allowing for the visualization of the topography of neurovascular unit components. [14] Electron microscopy techniques are, thus, invaluable for studying the precise cellular and subcellular interactions within the NVU. [15] However, it requires sample preparation involving fixation, dehydration, and staining, which can introduce artifacts, and it is not suitable for live or large-scale imaging due to its time-consuming nature.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is a non-invasive imaging technique that uses strong magnetic fields and radio waves to generate detailed images of the brain's anatomy and function. [16] It can provide information about blood flow, oxygenation levels, and structural characteristics of the neurovascular unit. The functional MRI (fMRI) allows researchers to study brain activity by measuring changes in blood oxygenation associated with neural activity, thus classifying it as a blood-oxygen-level-dependent imaging (BOLD imaging) technique. Diffusion MRI (dMRI) provides insights into the brain's structural connectivity by tracking the diffusion of water molecules in its tissue. [17] MRI, in general, has excellent spatial resolution and can be used for both human and animal studies, making it a valuable tool for studying the neurovascular unit in vivo. It has limited temporal resolution, though, and its ability to visualize finer cellular and molecular details within the neurovascular unit is relatively lower compared to microscopy techniques.

Optical coherence tomography

Optical coherence tomography (OCT) is an imaging technique that utilizes low-coherence interferometry to generate high-resolution cross-sectional images of biological tissues. [18] It can, thus, provide information about the microstructure and vascular network of the neurovascular unit. [19] More specifically, OCT has been used to study cerebral blood flow dynamics, changes in vessel diameter, and blood–brain barrier integrity. It also has real-time imaging capabilities and can, thus, be effectively applied in both clinical and preclinical settings. [19] Downsides of optical coherence tomography include limited depth penetration in highly scattering tissues and a lower resolution in increasing depth, which can limit its application in deep brain regions. [18]

Clinical significance

Neurovascular failure

Neurovascular failure, or neurovascular disease, refers to a range of conditions that negatively affect the function of blood vessels in the brain and spinal cord. [20] While the exact mechanisms behind neurovascular disease are unknown, people with inherited conditions (such as a family history of heart disease, diabetes, and/or high cholesterol), poor lifestyle choices, genetic changes during pregnancy, physical trauma, and other specific genetic characteristics are generally at higher risk. [20] In particular, neurovascular failure can be caused by problems arising in the blood vessels, including blockages (embolism), clot formation (thrombosis), narrowing (stenosis), and rupture (hemorrhage). In response to pathogenic stimuli, such as tissue hypoxia, signaling pathways involved in neurovascular coupling are impaired. [21] [22] Neuronal injury is often preceded by the expression and release of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF); in addition to this, the upregulation of astrocyte receptors in endothelial cells can stimulate endothelial proliferation and migration, which can dangerously increase blood–brain barrier (BBB) permeability. [21] Ultimately, vascular dysfunction results in decreased cerebral blood flow and abnormalities in the blood–brain barrier, which poses a threat to the normal functioning of the brain. [23]

Effects of neurovascular failure

Efficient blood supply to the brain is extremely significant to its normal functioning, and improper blood flow can lead to potentially devastating neurological consequences. [23] Alterations of vascular regulatory mechanisms lead to brain dysfunction and disease. The emerging view is that neurovascular dysfunction is a feature not only of cerebrovascular pathologies, such as stroke, but also of neurodegenerative conditions, such as Alzheimer's disease. [24] While studies are still ongoing to determine the precise effects of neurovascular failure, there is emerging evidence that neurovascular dysfunction plays a pivotal role in the degeneration of the nervous system, which contrasts the typical view that neurodegeneration is caused by intrinsic neuronal effects. [21] [25] The breakdown of neurovascular coupling (e.g., modulations in neuronal activity that cause changes in local blood flow [5] ) and the pathophysiology of the NVU is commonly observed across a wide variety of neurological and psychiatric disorders, including Alzheimer’s disease. [21] The combination of recent hypotheses and evidence suggests that the pathophysiology of the NVU may contribute to cognitive impairment and be an initiating trigger for neurological manifestations of diseases such as Alzheimer's and dementia. [26] [22] Ultimately, despite the vast amount of current literature supporting vascular contributions to neurological phenotypes, there is still much to be investigated, especially with respect to the effect of neurovasculature on neurological diseases; namely, whether the initiating event occurs at the neuronal level and "mobilizes" vascular response or the vascular event triggers neuronal dysfunction. [21] [22]

Alzheimer's disease

Alzheimer's disease (AD) is the most common type of dementia, a neurodegenerative disease with progressive impairment of behavioral and cognitive functions. [27] Neuropathologically, there are two major indicators of Alzheimer's: neurofibrillary tangles (NFTs) and an accumulation of amyloid β peptide (Aβ) in the brain, known as amyloid plaques, or around blood vessels, known as amyloid angiopathy. [28] There is growing support for the vascular hypothesis of AD, which posits that blood vessels are the origin for a variety of pathogenic pathways that lead to neuronal damage and AD. [29] Vascular risk factors can result in dysregulation of the neurovascular unit and hypoxia. Destruction of the organization of the blood–brain barrier, decreased cerebral blood flow, and the establishment of an inflammatory context often result in neuronal damage since these factors promote the aggregation of β-amyloid peptide in the brain. [29] During a review of various consortium data, it was shown that more than 30% of AD cases exhibit cerebrovascular disease on post-mortem examination, and almost all have evidence of cerebral amyloid angiopathy, microvascular degeneration, and white matter lesions. [30] Despite this data, it is still insufficient to reach a pathologic diagnosis, making it unclear whether AD is a cause or a consequence of neuronal dysfunction. [24] [29] However, considering that AD seems to include a combination of vascular and neurodegenerative processes and that disruption to the vascular physiology occurs early in the disease process, targeting the vascular component may help potentially decelerate the pathologic progression of AD. [31] Currently, only a few vascular targets have been the subject of large-scale randomised controlled trials. [31]

Huntington's disease

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an abnormal repetition of the CAG trinucleotide repeat within the Huntingtin gene (Htt). [32] Common features of Huntington's include involuntary movements (chorea), bradykinesia, psychiatric symptoms, and cognitive decline, all of which are accelerated through neuronal cell death. [33] [34] The idea that neurovascular impairments may contribute to early neuronal cell loss in Huntington’s disease has been attracting significant attention in the HD community. Reduced cerebral blood flow, increased small vessel density, and increased blood–brain barrier (BBB) permeability–all traits of neurovascular dysfunction–have been reported in both rodent and patient post-mortem tissue. [35] [36] [37] Preliminary findings support that neurovascular alterations occur in Huntington's disease and may contribute to its early neuropathology. [38] It has also been proposed that neurovascular dysregulation manifests earlier in Huntington's than other pathologies, triggering innate immune signaling and a reduction of protein levels critical for maintaining the blood–brain barrier. [39] While neurovascular failure in HD pathogenesis is still being tested, recent work supports clinical application. For example, immunohistological assays revealed vessel aberrations in brain tissue, establishing the early onset of such aberrations as a potential biomarker for early Huntington's diagnosis. [25]

Related Research Articles

<span class="mw-page-title-main">Cerebrovascular disease</span> Condition that affects the arteries that supply the brain

Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.

<span class="mw-page-title-main">Microangiopathy</span> Medical condition

Microangiopathy is a disease of the microvessels, small blood vessels in the microcirculation. It can be contrasted to macroangiopathies such as atherosclerosis, where large and medium-sized arteries are primarily affected.

<span class="mw-page-title-main">Haemodynamic response</span>

In haemodynamics, the body must respond to physical activities, external temperature, and other factors by homeostatically adjusting its blood flow to deliver nutrients such as oxygen and glucose to stressed tissues and allow them to function. Haemodynamic response (HR) allows the rapid delivery of blood to active neuronal tissues. The brain consumes large amounts of energy but does not have a reservoir of stored energy substrates. Since higher processes in the brain occur almost constantly, cerebral blood flow is essential for the maintenance of neurons, astrocytes, and other cells of the brain. This coupling between neuronal activity and blood flow is also referred to as neurovascular coupling.

<span class="mw-page-title-main">Astrogliosis</span> Increase in astrocytes in response to brain injury

Astrogliosis is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease. In healthy neural tissue, astrocytes play critical roles in energy provision, regulation of blood flow, homeostasis of extracellular fluid, homeostasis of ions and transmitters, regulation of synapse function and synaptic remodeling. Astrogliosis changes the molecular expression and morphology of astrocytes, in response to infection for example, in severe cases causing glial scar formation that may inhibit axon regeneration.

Cerebral atrophy is a common feature of many of the diseases that affect the brain. Atrophy of any tissue means a decrement in the size of the cell, which can be due to progressive loss of cytoplasmic proteins. In brain tissue, atrophy describes a loss of neurons and the connections between them. Brain atrophy can be classified into two main categories: generalized and focal atrophy. Generalized atrophy occurs across the entire brain whereas focal atrophy affects cells in a specific location. If the cerebral hemispheres are affected, conscious thought and voluntary processes may be impaired.

<span class="mw-page-title-main">Pericyte</span> Cells associated with capillary linings

Pericytes are multi-functional mural cells of the microcirculation that wrap around the endothelial cells that line the capillaries throughout the body. Pericytes are embedded in the basement membrane of blood capillaries, where they communicate with endothelial cells by means of both direct physical contact and paracrine signaling. The morphology, distribution, density and molecular fingerprints of pericytes vary between organs and vascular beds. Pericytes help to maintain homeostatic and hemostatic functions in the brain, one of the organs with higher pericyte coverage, and also sustain the blood–brain barrier. These cells are also a key component of the neurovascular unit, which includes endothelial cells, astrocytes, and neurons. Pericytes have been postulated to regulate capillary blood flow and the clearance and phagocytosis of cellular debris in vitro. Pericytes stabilize and monitor the maturation of endothelial cells by means of direct communication between the cell membrane as well as through paracrine signaling. A deficiency of pericytes in the central nervous system can cause increased permeability of the blood–brain barrier.

<span class="mw-page-title-main">Perivascular space</span>

A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain blood vessels in several organs, including the brain, potentially having an immunological function, but more broadly a dispersive role for neural and blood-derived messengers. The brain pia mater is reflected from the surface of the brain onto the surface of blood vessels in the subarachnoid space. In the brain, perivascular cuffs are regions of leukocyte aggregation in the perivascular spaces, usually found in patients with viral encephalitis.

<span class="mw-page-title-main">Watershed stroke</span> Medical condition

A watershed stroke is defined as a brain ischemia that is localized to the vulnerable border zones between the tissues supplied by the anterior, posterior and middle cerebral arteries. The actual blood stream blockage/restriction site can be located far away from the infarcts. Watershed locations are those border-zone regions in the brain supplied by the major cerebral arteries where blood supply is decreased. Watershed strokes are a concern because they comprise approximately 10% of all ischemic stroke cases. The watershed zones themselves are particularly susceptible to infarction from global ischemia as the distal nature of the vasculature predisposes these areas to be most sensitive to profound hypoperfusion.

Signal enhancement by extravascular water protons, or SEEP, is a contrast mechanism for functional magnetic resonance imaging (fMRI), which is an alternative to the more commonly employed BOLD contrast. This mechanism for image contrast changes corresponding to changes in neuronal activity was first proposed by Dr. Patrick Stroman in 2001. SEEP contrast is based on changes in tissue water content which arise from the increased production of extracellular fluid and swelling of neurons and glial cells at sites of neuronal activity. Because the dominant sources of MRI signal in biological tissues are water and lipids, an increase in tissue water content is reflected by a local increase in MR signal intensity. A correspondence between BOLD and SEEP signal changes, and sites of activity, has been observed in the brain and appears to arise from the common dependence on changes in local blood flow to cause a change in blood oxygenation or to produce extracellular fluid. The advantage of SEEP contrast is that it can be detected with MR imaging methods which are relatively insensitive to magnetic susceptibility differences between air, tissues, blood, and bone. Such susceptibility differences can give rise to spatial image distortions and areas of low signal, and magnetic susceptibility changes in blood give rise to the BOLD contrast for fMRI. The primary application of SEEP to date has been fMRI of the spinal cord because the bone/tissue interfaces around the spinal cord cause poor image quality with conventional fMRI methods. The disadvantages of SEEP compared to BOLD contrast are that it reveals more localized areas of activity, and in the brain the signal intensity changes are typically lower, and it can therefore be more difficult to detect.

Connectomics is the production and study of connectomes: comprehensive maps of connections within an organism's nervous system. More generally, it can be thought of as the study of neuronal wiring diagrams with a focus on how structural connectivity, individual synapses, cellular morphology, and cellular ultrastructure contribute to the make up of a network. The nervous system is a network made of billions of connections and these connections are responsible for our thoughts, emotions, actions, memories, function and dysfunction. Therefore, the study of connectomics aims to advance our understanding of mental health and cognition by understanding how cells in the nervous system are connected and communicate. Because these structures are extremely complex, methods within this field use a high-throughput application of functional and structural neural imaging, most commonly magnetic resonance imaging (MRI), electron microscopy, and histological techniques in order to increase the speed, efficiency, and resolution of these nervous system maps. To date, tens of large scale datasets have been collected spanning the nervous system including the various areas of cortex, cerebellum, the retina, the peripheral nervous system and neuromuscular junctions.

<span class="mw-page-title-main">Glymphatic system</span> System for waste clearance in the central nervous system of vertebrates

The glymphatic system is a system for waste clearance in the central nervous system (CNS) of vertebrates. According to this model, cerebrospinal fluid (CSF) flows into the paravascular space around cerebral arteries, combining with interstitial fluid (ISF) and parenchymal solutes, and exiting down venous paravascular spaces. The pathway consists of a para-arterial influx route for CSF to enter the brain parenchyma, coupled to a clearance mechanism for the removal of interstitial fluid (ISF) and extracellular solutes from the interstitial compartments of the brain and spinal cord. Exchange of solutes between CSF and ISF is driven primarily by arterial pulsation and regulated during sleep by the expansion and contraction of brain extracellular space. Clearance of soluble proteins, waste products, and excess extracellular fluid is accomplished through convective bulk flow of ISF, facilitated by astrocytic aquaporin 4 (AQP4) water channels.

<span class="mw-page-title-main">Cerebral atherosclerosis</span> Medical condition

Cerebral atherosclerosis is a type of atherosclerosis where build-up of plaque in the blood vessels of the brain occurs. Some of the main components of the plaques are connective tissue, extracellular matrix, including collagen, proteoglycans, fibronectin, and elastic fibers; crystalline cholesterol, cholesteryl esters, and phospholipids; cells such as monocyte derived macrophages, T-lymphocytes, and smooth muscle cells. The plaque that builds up can lead to further complications such as stroke, as the plaque disrupts blood flow within the intracranial arterioles. This causes the downstream sections of the brain that would normally be supplied by the blocked artery to suffer from ischemia. Diagnosis of the disease is normally done through imaging technology such as angiograms or magnetic resonance imaging. The risk of cerebral atherosclerosis and its associated diseases appears to increase with increasing age; however there are numerous factors that can be controlled in attempt to lessen risk.

Neuroangiogenesis is the coordinated growth of nerves and blood vessels. The nervous and blood vessel systems share guidance cues and cell-surface receptors allowing for this synchronised growth. The term neuroangiogenesis only came into use in 2002 and the process was previously known as neurovascular patterning. The combination of neurogenesis and angiogenesis is an essential part of embryonic development and early life. It is thought to have a role in pathologies such as endometriosis, brain tumors, and Alzheimer's disease.

<span class="mw-page-title-main">Pathophysiology of Parkinson's disease</span> Medical condition

The pathophysiology of Parkinson's disease is death of dopaminergic neurons as a result of changes in biological activity in the brain with respect to Parkinson's disease (PD). There are several proposed mechanisms for neuronal death in PD; however, not all of them are well understood. Five proposed major mechanisms for neuronal death in Parkinson's Disease include protein aggregation in Lewy bodies, disruption of autophagy, changes in cell metabolism or mitochondrial function, neuroinflammation, and blood–brain barrier (BBB) breakdown resulting in vascular leakiness.

<span class="mw-page-title-main">MRI pulse sequence</span>

An MRI pulse sequence in magnetic resonance imaging (MRI) is a particular setting of pulse sequences and pulsed field gradients, resulting in a particular image appearance.

<span class="mw-page-title-main">Functional ultrasound imaging</span>

Functional ultrasound imaging (fUS) is a medical ultrasound imaging technique of detecting or measuring changes in neural activities or metabolism, for example, the loci of brain activity, typically through measuring blood flow or hemodynamic changes. The method can be seen as an extension of Doppler imaging.

Chenghua Gu is a Professor of Neurobiology at the Harvard Medical School where her research focuses on the Blood–brain barrier. She is also part of the Harvard Brain Science Initiative and has won numerous awards for her groundbreaking research on the brain's vascular component.

<span class="mw-page-title-main">Hypertension and the brain</span>

Hypertension is a condition characterized by an elevated blood pressure in which the long term consequences include cardiovascular disease, kidney disease, adrenal gland tumors, vision impairment, memory loss, metabolic syndrome, stroke and dementia. It affects nearly 1 in 2 Americans and remains as a contributing cause of death in the United States. There are many genetic and environmental factors involved with the development of hypertension including genetics, diet, and stress.

VINE-seq is a method to isolate and molecularly characterize the vascular and perivascular cells of the human brain microvessels at single-nuclei resolution. This technique is achieved by combining various known laboratory-based strategies involving the mechanical dissociation of brain tissue samples into single cells, density gradient centrifugation and filtration to isolate nuclei of microvessels, fluorescence-activated cell sorting (FACs) of cellular populations and droplet-based single-nuclei RNA sequencing (drop-snRNA-seq). Altogether, this generates a single-nuclei transcriptomic profile of the various cell types present in the vasculature of the brain. Through processing and analyzing the single-nuclei transcriptomic data, the heterogeneity within and between cell types can be distinguished to construct the molecular landscape of the human brain vasculature that was not previously done before.

Nozomi Nishimura is an American biomedical engineer and associate professor at Cornell University. She was awarded the L'Oréal for Women in Science Fellowship in 2009.

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