Perivascular Components Research Articles

THE ORGANIZATION OF THE BASEMENT MEMBRANES IN THE CHOROID PLEXUS VILLI OF THE HUMAN BRAIN

THE ORGANIZATION OF THE BASEMENT MEMBRANES IN THE Choroid PLEXUS VILLI OF THE HUMAN BRAIN Authors O.V. Kirik 1*, O.S. Alekseeva 1,2, I.P. Grigorev 1, E.A. Fedorova 1, A.A. Beketova 1, D.E. Korzhevsky 1 Affiliation 1 Institute of Experimental Medicine, Saint Petersburg, Russian Federation 2 Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Saint Petersburg, Russian Federation Abstract BACKGROUND: The choroid plexus of the brain is the main component of the blood-cerebrospinal fluid barrier, separating these two biological fluids. Basement membranes of the choroid plexus have a special role in the implementation of barrier functions: they underlie the choroidal epithelium and capillary endothelium, and serve as an additional filter for substances penetrating from the blood into the cerebrospinal fluid. AIM: The purpose of this work was to study the organization of basement membranes in the villi of the human telencephalon choroid plexus using immunohistochemical detection of type IV collagen. METHODS: The study was performed on archival material from the choroid plexus of the human brain (age 29-50 years, n=10) using the immunohistochemical method for detecting type IV collagen. RESULTS: An immunohistochemical reaction using antibodies to type IV collagen showed the distribution of this protein in the subepithelial area and in the stroma of the choroid plexus villi. All immunopositive structures had clear contours; there was no reaction in the cell cytoplasm or a nonspecific background. Contacts of subepithelial and subcapillary basement membranes labeled with antibodies to type IV collagen were not detected. CONCLUSION: The study showed that the basement membranes of the villi of the choroid plexus of the human brain in the subepithelial and perivascular areas have a different organization. In this case, the union of the subepithelial and perivascular components containing type IV collagen, as a rule, does not occur.

Vimentin expression profiles in the testis and epididymis of prepubertal to aged African greater cane rat (Thryonomys swinderianus)

Introduction: Vimentin is a cytoskeletal protein that is expressed in different regions of the testicular and epididymal parenchyma with principal function of structural support. There is dearth of literature on testicular and epididymal vimentin expression in different ages of African greater cane rat (AGCR). Hence, this study investigated vimentin expression profiles in the testis and epididymis of prepubertal to aged AGCR. Methods: Twenty healthy AGCR procured from a commercial cane rat farm were used for this study. The rats were randomly divided into 4 groups (n=5) as follows; Group 1: prepubertal (1-4 months), Group 2: pubertal (5-11 months), Group 3: adult (12-30 months) and Group 4: aged (>30 months). Testicular and epididymal samples were harvested and processed for immunohistochemistry using anti-vimentin marker. Results: Testicular vimentin was expressed in the interstitium, perinuclear region and basal aspect of Sertoli cells and along the tip of elongated spermatids. In the various segments of the epididymis, vimentin expression was confined to the peritubular coat and interstitium (stroma and perivascular components). Vimentin staining intensity in the testis was significantly higher (p < 0.05) in the adult group relative to others and appeared to increase with age. For the epididymis, significantly higher (p < 0.05) vimentin intensity was observed prepubertally and decreased with age advancement. Significance: The result from this study has demonstrated that the testes of the adult AGCR as well as the epididymal segments of the prepubertal rat had increased vimentin intensities which are indicative of marked reproductive activity and robust content of undifferentiated cells respectively.

Coronary Artery Spasm and Perivascular Adipose Tissue Inflammation: Insights From Translational Imaging Research.

Perivascular adipose tissue, which constitutes perivascular components along with the adventitial vasa vasorum, plays an important role as a source of various inflammatory mediators in cardiovascular disease. Inflammatory changes in the coronary adventitia are thought to be involved in the pathogenesis of coronary artery spasm and vasospastic angina. Recent advances in translational research using non-invasive imaging modalities, including 18F-fluorodeoxyglucose PET and cardiac CT, have enabled us to visualise perivascular inflammation in the pathogenesis of coronary artery spasm. These modality approaches appear to be clinically useful as a non-invasive tool for examining the presence and severity of vasospastic angina.

Ultra-thin, aligned, free-standing nanofiber membranes to recapitulate multi-layered blood vessel/tissue interface for leukocyte infiltration study

Leukocyte infiltration plays critical roles in tissue inflammation for pathogen clearance and tumor eradication. This process is regulated by complex microenvironments in blood vessels, including inflamed endothelium, blood flow, and perivascular components. The role of perivascular components in leukocyte infiltration has not been systematically investigated until recently mostly due to lack of technology. In this work, we developed a three-dimensional multi-layered blood vessel/tissue model with a nanofiber membrane, enabling real-time visualization of dynamic leukocyte infiltration and subsequent interaction with perivascular macrophages. We directly fabricated a highly aligned, free-standing nanofiber membrane with an ultra-thin thickness of ∼1 μm in microfluidic systems. Coating the nanofiber membrane with matrigel showed synergetic topographical and biochemical effects on the reconstitution of a well-aligned endothelial monolayer on the membrane. Our 3D multi-layered blood vessel/tissue model will offer a powerful and versatile tool for investigating the mechanism of leukocyte tissue infiltration and subsequent immune responses.

Coronary Adventitial and Perivascular Adipose Tissue Inflammation in Patients With Vasospastic Angina

BackgroundRecent studies suggested that perivascular components, such as perivascular adipose tissue (PVAT) and adventitial vasa vasorum (VV), play an important role as a source of various inflammatory mediators in cardiovascular disease. ObjectivesThe authors tested their hypothesis that coronary artery spasm is associated with perivascular inflammation in patients with vasospastic angina (VSA) using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). MethodsThis study prospectively examined 27 consecutive VSA patients with acetylcholine-induced diffuse spasm in the left anterior descending artery (LAD) and 13 subjects with suspected angina but without organic coronary lesions or coronary spasm. Using CT coronary angiography and electrocardiogram-gated 18F-FDG PET/CT, coronary PVAT volume and coronary perivascular FDG uptake in the LAD were examined. In addition, adventitial VV formation in the LAD was examined with optical coherence tomography, and Rho-kinase activity was measured in circulating leukocytes. ResultsPatient characteristics were comparable between the 2 groups. CT coronary angiography and ECG-gated 18F-FDG PET/CT showed that coronary PVAT volume and coronary perivascular FDG uptake significantly increased in the VSA group compared with the non-VSA group. Furthermore, optical coherence tomography showed that adventitial VV formation significantly increased in the VSA group compared with the non-VSA group, as did Rho-kinase activity. Importantly, during the follow-up period with medical treatment, both coronary perivascular FDG uptake and Rho-kinase activity significantly decreased in the VSA group. ConclusionsThese results provide the first evidence that coronary spasm is associated with inflammation of coronary adventitia and PVAT, where 18F-FDG PET/CT could be useful for disease activity assessment. (Morphological and Functional Change of Coronary Perivascular Adipose Tissue in Vasospastic Angina [ADIPO-VSA Trial]; UMIN000016675)

Cellular distribution of interleukin-1α-immunoreactivity after MPTP intoxication in mice

In young rodents, peripheral injection of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) results in a dopaminergic nigrostriatal denervation (during the first week after injection), followed by a spontaneous dopaminergic reinnervation. Sprouting from residual neurons has been proposed to account for this event. It has been shown that an inflammatory process takes place during striatal dopaminergic denervation but its consequences remain controversial. Some clues notably indicate that interleukin (IL)-1α may participate in MPTP-induced inflammation and promote recovery. We therefore studied the immunohistochemical localization of IL-1α expression in the striatum and ventral mesencephalon at different times (1, 3, 6, 16, and 30 days) after MPTP injection in mice. IL-1α-immunoreactivity (ir) was observed in striatum, substantia nigra pars compacta, and ventral tegmental area. Apart from a few localization in mesencephalic activated microglia, IL-1α was almost exclusively found in activated astrocytes. However, in the striatal parenchyma, another component of IL-1α-ir colocalized with tyrosine hydroxylase (TH)-ir, a marker for dopaminergic neurons. Moreover, some parenchymal TH-positive axons were also found to express the growth cone-associated protein (GAP)-43, a marker for axonal growth cones. In the striatum, IL-1α-ir was also detected in a non-astrocytic perivascular component, with a distribution similar to GAP-43-ir. IL-1α could thus directly or indirectly influence striatal reorganization after MPTP.

Targeting therapy for migraine

This article reviews the overall pathophysiology of migraine and identifies specific pathways and potential targets for the acute treatment of migraine. This will include a review of our current understanding of the primary sites of action of commonly used antimigraine therapies, including triptans, analgesics (opioids, barbiturates, and narcotics), anti-inflammatories (NSAIDs, COX-2 inhibitors), and potential future treatments. The article closes with the suggestion that targeting multiple migraine mechanisms may enhance the effectiveness of antimigraine treatment compared to traditional monotherapeutic approaches. Over the past 25 years the field of migraine research has witnessed an explosion of information on the understanding of the pathophysiology and mechanisms involved in the disorder. Advances in molecular biology, genomic science, and imaging techniques have helped to better define pathways involved in the migraine process. Head pain is generated when pain-sensitive intracranial structures are stimulated. These include vascular, meningeal, and neural elements. The circle of Willis and proximal cerebral arteries, middle meningeal, superficial, and trochlear arteries, superior sagittal sinus, and sylvian veins are all vascular pain structures.1,2 Neuronal structures that mediate head pain include the trigeminal, glossopharyngeal, and vagus cranial nerves. Finally, the cranial meninges, and especially the perivascular components of the dura, are important sources of headache. Pain signals are transmitted from the nociceptive structures, mostly via A-δ- and C-fibers that contain glutamate and neuropeptides such as calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A (NKA). Cat studies indicate that the middle meningeal artery nociceptive fibers travel through the ophthalmic branch of the trigeminal nerve to the projection area of the ipsilateral ganglion. On the other hand, fibers from the dura of the middle cranial fossa travel to the mandibular projection area of the ipsilateral trigeminal ganglion. From the first relay in the trigeminal ganglion, fibers project centrally to synapse on secondary sensory neurons …

Glioma-associated Antigen Expression in Oligodendroglial Neoplasms: Tenascin and Epidermal Growth Factor Receptor

Epidermal growth factor receptor (EGFR), its variant, EGFRvIII, and tenascin are glioma-associated antigens that are hyperexpressed by neoplastic glial cells relative to normal brain, making them attractive antigenic targets for immunotherapy. Preliminary surveys indicate that oligodendroglial tumors also produce these proteins, although the exact patterns and degrees of reactivity are not known. In this study we examined the immunoreactivity of tenascin among 50 oligodendroglial tumors, including 25 well-differentiated oligodendrogliomas (WDOs) and 12 glioblastomas (GBMs) exhibiting high proportions of oligodendroglia-like cells. We used well-characterized immunoreagents with defined specificities against the target antigens on formalin-fixed, paraffin-embedded archival tissue. The tumors were graded according to WHO guidelines. Immunoreactivity was reported on a 1-3 scale according to staining intensity multiplied by a 1-3 distribution scale distribution within tumor as focal (1), multifocal (2), and diffuse (3) for both the parenchymal and the perivascular components. Although there is considerable overlap in antigen production among the grades of tumor, this study establishes the production of tenascin and wild-type EGFR (but not EGFR vIII) in oligodendroglial neoplasms and supports the concept that antigen production increases with tumor grade.

Microcirculatory homeostasis 1930-1990: insight into microcirculatory readjustments provided by studies on the peripheral circulatory insufficiency of the shock syndrome.

The present overview is intended to serve several purposes. It highlights efforts over the years to resolve the difficult key issues raised by August Krogh in the 1930s and by the urgent need created in the 1940s and 1950s by World War II to come to grips with the basic problems underlying the collapse of tissue perfusion in the syndrome of circulatory shock. The complex operational issues raised by circulatory insufficiency at the systemic, as well as the local tissue level, during the shock syndrome, are used as a framework to keep in perspective the impact of advances in methodology, ultrastructure, and in recent years in molecular biology on microvascular research. In view of the current continuing need to integrate the newly emerging body of in vitro information into specific aspects of the operation of the peripheral vascular tree, emphasis is placed on the advances in dealing with data provided by in vivo microscopy of selected tissues. This overall review had made it clear that a top priority remains the need to separate the effects of systemic and locally derived readjustments, and to identify the basis for the substantial differences in cellular behavior exhibited by the vascular and perivascular components of the various organs and tissues of the body that can serve as predisposing factors in regional pathophysiology.

Nerve growth factor receptor in neural lobe of rat pituitary gland: immunohistochemical localization, biochemical characterization and regulation

Nerve growth factor-receptor immunoreactivity was detected in the neural lobe of the pituitary gland in developing and adult rats of both sexes. The presence of nerve growth factor receptor in the neural lobe was further verified by a quantitative 125I-nerve growth factor/crosslink/immunoprecipitation assay and subsequent visualization by SDS-PAGE autoradiography. Nerve growth factor-receptor immunoreactivity was detected in the neural lobe of postnatal 5-day-old rats, had increased by 2 months and was much higher in 1-year-old rats. In 2-month-old rats, no immunoreactivity was observed in anterior or intermediate lobes. Pituitary stalk transection in young adult rats greatly increased the expression of nerve growth factor-receptor immunoreactivity in the neural lobe, although the staining pattern remained the same. This increase began 3 days after surgery, and reached peak levels at approximately 15 days. Other physiological or non-physiological changes did not alter the nerve growth factor-receptor immunoreactivity in the neural lobe; these changes included dehydration, pregnancy and lactation, castration of male rats, bilateral superior cervical ganglionectomy and intraventricular injection of colchicine. Intravenously injected 125I-nerve growth factor was specifically accumulated in both normal and denervated neural lobe. Nerve growth factor-receptor immunohistochemical electron microscopy showed that the receptor-positive cells are fusiform and found both inside and outside the basal lamina that delimits the neural lobe parenchyma. Based upon the anatomical localization, morphology and response to axotomy, we identify, at least the perivascular component, as microglia. These data suggest a role for nerve growth factor and/or nerve growth factor receptor in microglial function.

Computerized three-dimensional reconstruction of the developing blood-brain barrier.

Computer-aided techniques for three-dimensional reconstruction of images were employed in a morphological and morphometrical study of blood-brain barrier (BBB) development in the microvasculature of the chick embryo optic tectum. The method proved very useful for understanding the spatial relationships between BBB vascular and perivascular components, and of their modifications during embryonic life. The results indicate that the perivascular astrocytic endfeet, the main periendothelial components of the BBB, appear on the 14th incubation day and form an almost continuous perivascular envelope at hatching time.

Endothelial and perivascular anionic sites during immediate transient vascular leakage.

To study surface charge characteristics of small blood vessels and perivascular components in vivo, rat cremaster vessels exposed to serotonin or mild thermal injury were labelled with systemically injected cationized ferritin and studied by electron microscopy. Leaky vessels showed increased density of anionic sites on the luminal endothelial plasma membrane, compared to controls. Binding of cationized ferritin and the increased density of anionic sites in leaky vessels occurred in the absence of serum factors; albumin diminished both phenomena. Anionic sites were also demonstrated a) on the surface membranes of open interendothelial junctions, b) on the attachment surface of endothelial cells, c) along the vascular basal lamina, perimysial membrane, and interstitial collagen. The biological significance of these findings is considered in relation to ligand-anionic sites interaction, inflammation, vascular permeability, and thrombosis.

Some morphological considerations of the blood-brain barrier

The fine structure of the perivascular components of the CNS is reviewed. Recent work using electron-opaque markers comparing the passage of large molecules and colloidal particles in brain capillaries with other sites is discussed. The maintenance of a barrier to certain substances is partly dependent on the maintenance of a closed gap between the endothelial cells of the brain. In this respect, it is concluded that the properties of the capillary endothelial cells of the brain differ from those in other sites.