scholarly journals Crosstalk between Inflammation and the BBB in Stroke

2020 ◽  
Vol 18 (12) ◽  
pp. 1227-1236
Author(s):  
Yuyou Huang ◽  
Shengpan Chen ◽  
Yumin Luo ◽  
Ziping Han
Keyword(s):  
Cerebral Ischemia ◽  
Neurovascular Unit ◽  
Circulatory System ◽  
Inflammatory Cells ◽  
Stroke Outcomes ◽  
Targeted Interventions ◽  
Repair Mechanisms ◽  
The Central Nervous System ◽  
Late Reperfusion ◽  
Astrocyte Endfeet

The blood-brain barrier (BBB), which is located at the interface between the central nervous system (CNS) and the circulatory system, is instrumental in establishing and maintaining the microenvironmental homeostasis of the CNS. BBB disruption following stroke promotes inflammation by enabling leukocytes, T cells and other immune cells to migrate via both the paracellular and transcellular routes across the BBB and to infiltrate the CNS parenchyma. Leukocytes promote the removal of necrotic tissues and neuronal recovery, but they also aggravate BBB injury and exacerbate stroke outcomes, especially after late reperfusion. Moreover, the swelling of astrocyte endfeet is thought to contribute to the ‘no-reflow’ phenomenon observed after cerebral ischemia, that is, blood flow cannot return to capillaries after recanalization of large blood vessels. Pericyte recruitment and subsequent coverage of endothelial cells (ECs) alleviate BBB disruption, which causes the transmigration of inflammatory cells across the BBB to be a dynamic process. Furthermore, interneurons and perivascular microglia also make contacts with ECs, astrocytes and pericytes to establish the neurovascular unit. BBB-derived factors after cerebral ischemia triggered microglial activation. During the later stage of injury, microglia remain associated with brain ECs and contribute to repair mechanisms, including postinjury angiogenesis, by acquiring a protective phenotype, which possibly occurs through the release of microglia-derived soluble factors. Taken together, we reviewed dynamic and bidirectional crosstalk between inflammation and the BBB during stroke and revealed targeted interventions based on the crosstalk between inflammation and the BBB, which will provide novel insights for developing new therapeutic strategies.

scholarly journals Early Loss of Pericytes and Perivascular Stromal Cell-Induced Scar Formation after Stroke

2012 ◽  
Vol 33 (3) ◽  
pp. 428-439 ◽  
Author(s):  
Francisco Fernández-Klett ◽  
Jason R Potas ◽  
Diana Hilpert ◽  
Katja Blazej ◽  
Josefine Radke ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Stromal Cells ◽  
Neurovascular Unit ◽  
Growth Factor Receptor ◽  
Scar Formation ◽  
Peripheral Tissues ◽  
Cord Injury ◽  
Repair Mechanisms ◽  
Human Stroke ◽  
Novel Target

Despite its limited regenerative capacity, the central nervous system (CNS) shares more repair mechanisms with peripheral tissues than previously recognized. Scar formation is a ubiquitous healing mechanism aimed at patching tissue defects via the generation of fibrous extracellular matrix (ECM). This process, orchestrated by stromal cells, can unfavorably affect the capacity of tissues to restore function. Vascular mural cells have been found to contribute to scarring after spinal cord injury. In the case of stroke, little is known about the responses of pericytes (PCs) and stromal cells. Here, we show that capillary PCs are rapidly lost after cerebral ischemia in both experimental and human stroke. Coincident with this loss is a massive proliferation of resident platelet-derived growth factor receptor beta (PDGFRβ)+ and CD105+ stromal cells, which originate from the neurovascular unit and deposit ECM in the ischemic mouse brain. The presence of PDGFRβ+ stromal cells demarcates a fibrotic, contracted, and macrophage-laden lesion core from the rim of hypertrophic astroglia in both experimental and human stroke. We suggest that a previously unrecognized population of CNS-resident stromal cells drives a dynamic process of scarring after cerebral ischemia, which appears distinct from the glial scar and represents a novel target for regenerative stroke therapies.

scholarly journals Stroke and the neurovascular unit: glial cells, sex differences, and hypertension

2019 ◽  
Vol 316 (3) ◽  
pp. C325-C339 ◽  
Author(s):  
Helena W. Morrison ◽  
Jessica A. Filosa
Keyword(s):  
Neurovascular Unit ◽  
Cell Communication ◽  
Cell Loss ◽  
Epidemiological Studies ◽  
Human Condition ◽  
Cellular Mechanisms ◽  
Stroke Outcomes ◽  
Repair Mechanisms ◽  
Stroke Models ◽  
The Impact

A functional neurovascular unit (NVU) is central to meeting the brain’s dynamic metabolic needs. Poststroke damage to the NVU within the ipsilateral hemisphere ranges from cell dysfunction to complete cell loss. Thus, understanding poststroke cell-cell communication within the NVU is of critical importance. Loss of coordinated NVU function exacerbates ischemic injury. However, particular cells of the NVU (e.g., astrocytes) and those with ancillary roles (e.g., microglia) also contribute to repair mechanisms. Epidemiological studies support the notion that infarct size and recovery outcomes are heterogeneous and greatly influenced by modifiable and nonmodifiable factors such as sex and the co-morbid condition common to stroke: hypertension. The mechanisms whereby sex and hypertension modulate NVU function are explored, to some extent, in preclinical laboratory studies. We present a review of the NVU in the context of ischemic stroke with a focus on glial contributions to NVU function and dysfunction. We explore the impact of sex and hypertension as modifiable and nonmodifiable risk factors and the underlying cellular mechanisms that may underlie heterogeneous stroke outcomes. Most of the preclinical investigative studies of poststroke NVU dysfunction are carried out primarily in male stroke models lacking underlying co-morbid conditions, which is very different from the human condition. As such, the evolution of translational medicine to target the NVU for improved stroke outcomes remains elusive; however, it is attainable with further research.

scholarly journals COVID-19 Vaccination: From Interesting Agent to the Patient

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 120
Author(s):  
Anis Daou
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gastrointestinal Tract ◽  
Circulatory System ◽  
The Novel ◽  
Lead Compound ◽  
Fda Approval ◽  
The World ◽  
The Central Nervous System ◽  
Novel Coronavirus

The vaccination for the novel Coronavirus (COVID-19) is undergoing its final stages of analysis and testing. It is an impressive feat under the circumstances that we are on the verge of a potential breakthrough vaccination. This will help reduce the stress for millions of people around the globe, helping to restore worldwide normalcy. In this review, the analysis looks into how the new branch of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) came into the forefront of the world like a pandemic. This review will break down the details of what COVID-19 is, the viral family it belongs to and its background of how this family of viruses alters bodily functions by attacking vital human respiratory organs, the circulatory system, the central nervous system and the gastrointestinal tract. This review also looks at the process a new drug analogue undergoes, from (i) being a promising lead compound to (ii) being released into the market, from the drug development and discovery stage right through to FDA approval and aftermarket research. This review also addresses viable reasoning as to why the SARS-CoV-2 vaccine may have taken much less time than normal in order for it to be released for use.

scholarly journals Astroglial Integrins in the Development and Regulation of Neurovascular Units

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hironobu Tanigami ◽  
Takayuki Okamoto ◽  
Yuichi Yasue ◽  
Motomu Shimaoka
Keyword(s):  
Central Nervous System ◽  
Cell Adhesion Molecules ◽  
Energy Demand ◽  
Vascular Tone ◽  
Neurovascular Unit ◽  
Neuronal Synapses ◽  
The Central Nervous System ◽  
The Brain ◽  
Signaling Activity ◽  
Cerebral Vascular

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.

Overview of existing in vitro BBB models: advantages and disadvantages, current state and future prospects

2021 ◽  
Vol 10 (3) ◽  
pp. 109-120
Author(s):  
A. I. Mosiagina ◽  
A. V. Morgun ◽  
A. B. Salmina
Keyword(s):  
Neurovascular Unit ◽  
Clinical Trial Data ◽  
Advantages And Disadvantages ◽  
The Central Nervous System ◽  
Complex Relationships ◽  
On Chip ◽  
Induced Pluripotent ◽  
Level Of Understanding

There is growing research focusing on endothelial cells as separate units of the blood-brain barrier (BBB), and on the complex relationships between different types of cells within a neurovascular unit. To conduct this type of studies, researches use vastly different in vitro BBB models. The main objective of such models is to study the BBB permeability for different molecules, and to advance the current level of understanding the mechanisms of disease and to develop methods of targeted therapy for the central nervous system. The analysis of the existing Abstract in vitro BBB models and their advantages/disadvantages was conducted using the clinical trial data obtained in Russian/foreign countries. In this review, the authors highlight the most relevant assessment parameters and propose a unified classification of in vitro BBB models. According to the performed analysis, there is a tendency to move from 2D BBB models based on semipermeable inserts to 3D BBB spheroid and microfluidic organ-on-chip models. Moreover, the use of human induced pluripotent stem cells instead of animal primary cells will make it possible to reliably scale the results obtained in vitro to conditions in vivo.

scholarly journals Regenerative Effects of Heme Oxygenase Metabolites on Neuroinflammatory Diseases

2018 ◽  
Vol 20 (1) ◽  
pp. 78 ◽  
Author(s):  
Huiju Lee ◽  
Yoon Choi
Keyword(s):  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Neurovascular Unit ◽  
Vascular Diseases ◽  
Cell Types ◽  
Cns Injury ◽  
Perivascular Cells ◽  
Major Barrier ◽  
The Central Nervous System

Heme oxygenase (HO) catabolizes heme to produce HO metabolites, such as carbon monoxide (CO) and bilirubin (BR), which have gained recognition as biological signal transduction effectors. The neurovascular unit refers to a highly evolved network among endothelial cells, pericytes, astrocytes, microglia, neurons, and neural stem cells in the central nervous system (CNS). Proper communication and functional circuitry in these diverse cell types is essential for effective CNS homeostasis. Neuroinflammation is associated with the vascular pathogenesis of many CNS disorders. CNS injury elicits responses from activated glia (e.g., astrocytes, oligodendrocytes, and microglia) and from damaged perivascular cells (e.g., pericytes and endothelial cells). Most brain lesions cause extensive proliferation and growth of existing glial cells around the site of injury, leading to reactions causing glial scarring, which may act as a major barrier to neuronal regrowth in the CNS. In addition, damaged perivascular cells lead to the breakdown of the blood-neural barrier, and an increase in immune activation, activated glia, and neuroinflammation. The present review discusses the regenerative role of HO metabolites, such as CO and BR, in various vascular diseases of the CNS such as stroke, traumatic brain injury, diabetic retinopathy, and Alzheimer’s disease, and the role of several other signaling molecules.

scholarly journals Regional CNS responses to IFN-γ determine lesion localization patterns during EAE pathogenesis

2008 ◽  
Vol 205 (11) ◽  
pp. 2633-2642 ◽  
Author(s):  
Jason R. Lees ◽  
Paul T. Golumbek ◽  
Julia Sim ◽  
Denise Dorsey ◽  
John H. Russell
Keyword(s):  
Spinal Cord ◽  
T Cells ◽  
Brain Stem ◽  
Clinical Outcomes ◽  
Clinical Symptoms ◽  
Inflammatory Cells ◽  
Th1 Cells ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Ifn Γ

The localization of inflammatory foci within the cerebellum is correlated to severe clinical outcomes in multiple sclerosis (MS). Previous studies of experimental autoimmune encephalomyelitis (EAE), a model of MS, revealed distinct clinical outcomes correlated with the capacity of the animal to produce IFN-γ. Outcomes were linked to localization of inflammatory cells in either the spinal cord (wild type [WT]) or the cerebellum and brain stem (IFN-γ deficient). We demonstrate, using an adoptive transfer system, that the ability of the central nervous system (CNS) to sense pathogenic T cell–produced IFN-γ during EAE initiation determines the sites of CNS pathogenesis. Transfer of WT Th1 cells into IFN-γ receptor–deficient mice results in pathogenic invasion of the brain stem and cerebellum with attendant clinical symptoms, which are identical to the disease observed after transfer of IFN-γ–deficient T cells to WT hosts. Inflammation of the spinal cord associated with classical EAE is abrogated in both IFN-γ–deficient systems. Cotransfer of CNS antigen-specific WT Th1 cells with IFN-γ–deficient T cells is sufficient to restore spinal cord invasion and block cerebellar and brain stem invasion. These data demonstrate that interaction between IFN-γ and host CNS cells during the initiation of EAE can selectively promote or suppress neuroinflammation and pathogenesis.

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