Wide Perivascular Spaces Research Articles

Prophylactic and Ameliorative Effect of N-Acetylcysteine on Doxorubicin-Induced Neurotoxicity in Wister Rats

Doxorubicin (DOX) is an anthracycline antibiotic and a quinone-containing chemotherapeutic drug used for various types of cancers. However, as with most anticancer drugs, it causes many toxic effects, one of them is cognitive impairment. The present study investigated the prophylactic and ameliorative effect of n-acetylcysteine (NAC) against DOX-induced neurotoxicity in rats. Rats were divided into four groups. Control group: rats received saline. NAC treated group: rats received NAC (100 mg/kg, p.o.) daily for 35 days. DOX-treated group: rats received DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28. DOX+NAC treated group 1: rats received NAC (100 mg/kg, p.o.) daily for 35 days and DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28). DOX+NAC treated group 2: rats received NAC (100 mg/kg, p.o.) daily started at the 7th day of the experiment till the end of the experiment and DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28. The present results showed a significant reduction in the body weight, which was associated with a significant increase in brain to body weight ratio in DOX-treated rats. Tumor necrosis factor (TNF-α) level, malondialdehyde (MDA) and total protein levels were significantly elevated. Whilst, reduced glutathione (GSH) and glutathione peroxidase (GPx) levels were significantly decreased. Moreover, there were histopathological abnormalities in the brain tissue of DOX-treated rats, as most of the neurons degenerated and the blood vessels surrounded with wide perivascular spaces. In addition, the neuropil was vacuolated. The present study demonstrated that NAC has a neuroprotective effect on the brain damage induced by DOX, through inhibition of inflammation and oxidative stress. This neuroprotective effect was more pronounced in DOX+NAC treated group 1, as it produced a significant increase in brain GSH and GPx levels and more improvement in the histopathological abnormality compared to DOX+NAC treated group 2.

Advances in Understanding of Structural Reorganization in the Hypothalamic Neurosecretory System.

The hypothalamic neurosecretory system synthesizes neuropeptides in hypothalamic nuclei and releases them from axonal terminals into the circulation in the neurohypophysis (NH) and median eminence (ME). This system plays a crucial role in regulating body fluid homeostasis and social behaviors as well as reproduction, growth, metabolism, and stress responses, and activity-dependent structural reorganization has been reported. Current knowledge on dynamic structural reorganization in the NH and ME, in which the axonal terminals of neurosecretory neurons directly contact the basement membrane (BM) of a fenestrated vasculature, is discussed herein. Glial cells, pituicytes in the NH and tanycytes in the ME, engulf axonal terminals and interpose their cellular processes between axonal terminals and the BM when hormonal demands are low. Increasing demands for neurosecretion result in the retraction of the cellular processes of glial cells from axonal terminals and the BM, permitting increased neurovascular contact. The shape conversion of pituicytes and tanycytes is mediated by neurotransmitters and sex steroid hormones, respectively. The NH and ME have a rough vascular BM profile of wide perivascular spaces and specialized extension structures called “perivascular protrusions.” Perivascular protrusions, the insides of which are occupied by the cellular processes of vascular mural cells pericytes, contribute to increasing neurovascular contact and, thus, the efficient diffusion of hypothalamic neuropeptides. A chronic physiological stimulation has been shown to increase perivascular protrusions via the shape conversion of pericytes and the profile of the vascular surface. Continuous angiogenesis occurs in the NH and ME of healthy normal adult rodents depending on the signaling of vascular endothelial growth factor (VEGF). The inhibition of VEGF signaling suppresses the proliferation of endothelial cells (ECs) and promotes their apoptosis, which results in decreases in the population of ECs and axonal terminals. Pituicytes and tanycytes are continuously replaced by the proliferation and differentiation of stem/progenitor cells, which may be regulated by matching those of ECs and axonal terminals. In conclusion, structural reorganization in the NH and ME is caused by the activity-dependent shape conversion of glial cells and vascular mural cells as well as the proliferation of endothelial and glial cells by angiogenesis and gliogenesis, respectively.

Imaging in cutis laxa syndrome caused by a dominant negative ALDH18A1 mutation, with hypotheses for intracranial vascular tortuosity andwide perivascular spaces.

The autosomal dominant progeroid form of cutis laxa is a recently identified multiple congenital anomaly disorder characterized by thin, wrinkled skin, a progeroid appearance, intra-uterine growth retardation, postnatal growth restriction, psychomotor developmental delay, microcephaly, cataract, hypotonia and contractures. De novo heterozygous mutations in ALDH18A1 have been described in this condition. We present neuroimaging abnormalities in three patients. One patient had intracranial arterial and venous tortuosity, widened ventricular and extra-axial cerebrospinal fluid (CSF) spaces, wide perivascular spaces and increased T2 signal intensity in the cerebral white matter over time. The second patient had vascular tortuosity. The third patient had prominent ventricular and extra-axial cerebrospinal fluid (CSF) spaces on CT. We propose an embryological mechanism for the development of intracranial vascular tortuosity and discuss the anatomical basis of wide perivascular spaces in relation to this syndrome. Although we do not know the clinical implications of these cerebral vascular anomalies, we suggest inclusion of neuroimaging in the baseline evaluation of these patients.

Microarchitecture of the cat testis with special reference to Leydig cells: a three-dimensional study by alkali maceration method and scanning electron microscopy.

Testes from adult cats were studied by means of parallel transmission and scanning electron microscopy (SEM) after NaOH digestion technique, which selectively removed connective tissues or cells. The testis is covered by a dense fibroconnective tunica albuginea that partially divides the organ in lobules by sending septa into the parenchyma. The lamina propria of the seminiferous tubules consisted of one or two rows of cells. The interstitium was made up of randomly arranged collagen bundles. The most significant feature was the numerous Leydig cells rich in lipid droplets and displaying epithelioid features. Following alkali digestion and SEM these cells showed a cord-like arrangement. The cords were formed by one or two closely apposed cells, in between which some labyrinthine or canalicular-like spaces were left that in some areas opened in wide perivascular spaces. This particular arrangement of Leydig cells and the labyrinthine intercellular spaces is very likely designed to improve cell secretion of hormones, facilitating their transport into the blood, as well as the traffic of fluids and metabolites. The present techniques allowed the visualization of a real three-dimensional testicular microarchitecture and microtopography, not detectable with other methods. Such a study may help to better highlight the testicular morphophysiology.

Recent advances in andrology research: physiopathology and clinical application to fertility and infertility.

Sperm maturation depends on androgen and is mediated by several unidentified epididymal factors: glycoproteins and metabolites affecting acrosomal stability and fertilizing potential of capacitated sperm. Several genes encoding human epididymis-specific proteins have been described. One of the cloned epididymal cDNA encodes a polypeptide designated as HE4 with an estimated molecular mass of 10,000. Leydig cells are rich in lipid droplets and display epithelioid features. These cells have a cord-like arrangement; the cords are formed by one or two closely apposed cells. In between these cells, labyrinthine or canalicular-like spaces are opened in wide perivascular spaces that improve cell secretion of hormones and facilitate their transport into the blood, as well as the traffic of fluids and metabolites. Coagulation and liquefaction in human semen plays an important role in the capacitation of semen. The liquefaction of semen is retarded by the powerful synthetic inhibitors of 6-amidino-2-naphtyl-p-guanidinobenzoate dimethansulfonate.

Organum vasculosum laminae terminalis (OVLT) in rabbit and rat: topographic studies.

The microcirculation and fine structure of the rabbit and rat organum vasculosum laminae terminalis (OVLT) were examined by light microscopy and scanning and transmission electron microscopy. In both animals, the microcirculation is composed of a superficial and a deep vascular bed but the system is more complex and extensive in the rabbit. This was particularly true of the deep vascular bed. In the rabbit, the deep bed is composed of fenestrated capillaries, which are arranged in glomerular tufts surrounded by very wide perivascular spaces (PVS). In contrast, the deep vascular bed of the rat OVLT usually consists of only one or two small vessels. These are either fenestrated and surrounded by a PVS or lined by continuous endothelium with only a few fenestrae and without a dilated PVS. A corresponding difference was seen in the contours of the ventricular surface. It is much more irregular in the rabbit than in the rat and numerous bulges reflect the underlying vascular tufts and pockets of PVS in the rabbit. Supraependymal cells are present in both species and two sizes of them occur in the rabbit. The results demonstrate that the microcirculation of the OVLT is more elaborate and more highly developed in the rabbit than in the rat. We suggest that this might result in a different neurohemal microenvironment and, ultimately, in functional differences.

The fine structure of the area postrema of the sheep.

The ultrastructural features of the area postrema (AP) were investigated in the suckling lamb, weaned lamb and adult sheep. No morphological differences were observed between lambs and sheep. Unciliated ependymal cells, linked by zonulae adherentes-type junctions and gap junctions, cover the AP ventricular surface. Clusters of pyriform neurons, glial cells, and axons are present in the parenchyma. The blood vessels are surrounded by wide perivascular spaces, which present an inner and outer basal lamina. The capillaries are of the fenestrated type. Perivascular glial cells rest on the outer basal lamina of the perivascular space and form a continuous ensheathment with their cell bodies or with flattened interdigitating processes. Along adjacent perivascular glial processes gap junctions are present. From our ultrastructural observations it appears that the overall cellular morphology of AP of the sheep does not differ substantially from that of monogastric mammals.

Axo-glial relations in the retina-optic nerve junction of the adult rat: electron-microscopic observations

The retina-optic nerve junction (ROJ) was examined by electron microscopy in adult rats, with particular emphasis on the unmyelinated-myelinated nerve fibre transition. Both single sections and serial sections were used. The non-retinal part of the ROJ is covered by an extensively folded glia limitans, facing the choroidea, sclera and pia mater. The blood vessels within the ROJ follow a transverse course and are surrounded by unusually wide perivascular spaces with a glia limitans-like outer delimitation. The endothelial cells exhibit numerous pinocytotic vesicles on their abluminal aspect. In the unmyelinated part of the ROJ the axons are embedded in an extensive meshwork of fibrous astrocytic processes. Some unmyelinated axons exhibit patches of axolemmal undercoating with externally associated astrocytic processes. Typical oligodendrocytes are not found, but a few small dark glial cells of unknown identity can be observed. Atypical ensheathment and myelination of axons at this level by ectopic Schwann cells occurred in one case. In the transition segment of the ROJ a pattern similar to that along dysmyelinated axons is observed, including aberrant axo-glial contacts, unusually thin and short myelin sheaths, intercalated unmyelinated segments, distorted myelin termination regions, bizarre paranodes and myelin termination regions without associated nodally differentiated axolemma. Neither sheath length nor number of myelin lamellae is related to axon diameter in the transition region. Axon diameter tends to be somewhat larger at myelinated than unmyelinated levels of the same axon. We suggest that the unusual axo-glial relations in this region are due to a deficient proliferation and differentiation of oligodendroglial cells, and that the pattern of glial ensheathment in the ROJ might be a consequence of the locally deficient blood-brain barrier.

Blood vessels surrounded by connective tissue (perivascular space) in the brain of Lepidosteus (Ganoikei) and some teleost fishes.

Blood vessels surrounded by unusually wide perivascular spaces rich in connective tissue were observed in the brain of Lepidosteus (Ganoidei). Connective-tissue sheaths measuring up to 13 μm in width enclose arterioles and venules (40–70 μm in diameter), and even capillaries may be encompassed by a cuff formed by collagen fibers. Blood vessels with wide perivascular spaces are mainly located in the subependymal layer of the lateral ventricles, near the mesencephalic aqueduct and in the folded basal lining of the fourth ventricle. At the light-microscopic level these vessels do not show any distinct contact with nervous elements (axons). Some other brain regions of Lepidosteus, e.g. mesencephalic tectum, are supplied by a conventional type of capillaries, free of connective-tissue linings. For comparative reasons, brains of several selachian and teleostean species were examined with comparable histological methods. Distinct perivascular spaces were found in the pike, in the trout and in the eel. They are considerably richer in connective tissue than the occasionally observed narrow perivascular spaces in the shark. The significance of the abundant perivascular connective tissue in the brain of Lepidosteus is open to discussion; structural and functional problems of the brain-blood-barrier have been reviewed in this context. The brain of Lepidosteus appears to be a very suitable model for studies of blood supply, vascular ultrastructure and blood-brain-barrier functions.

Connective tissue in pericapillary spaces of the human spinal cord.

The ultrastructure of the spinal cord capillary bed in man was studied. About 70% of all vessels without muscular wall or adventitia and showing a diameter of not more than 10 μ have wide perivascular spaces containing large amounts of connective tissue. The vessels of both grey and white matter show this phenomenon. The implications of these findings are discussed.

Fine structure of the vessels of the hypophysial portal system of the white-crowned sparrow, Zonotrichia leucophrys gambelii.

The angioarchitecture of the hypophysial portal system of the White-crowned Sparrow, Zonotrichia leucophrys gambelii, was investigated by electron microscopy in conjunction with light microscopy of serial thick sections. The small arteries or arterioles supplying the primary capillary plexus of the median eminence have the typical form of arterioles. The vessels of the primary capillary plexus, on the surface of the median eminence, with their many fenestrations and pinocytotic vesicles, are typical of the form of capillary usually found in other endocrine organs. The portal vessels in the pars tuberalis have wide perivascular spaces between the basement membrane of the endothelium and that of parenchymal lobules of the pars tuberalis. These perivascular spaces are occupied usually by the perivascular cells, but sometimes contain erythrocytes. The endothelial cells of the portal vessels often protrude into vascular lumen giving the appearance of valve-like structures. These may have a role in the regulation of blood flow. The endothelial cells of the portal vessels are invested by a definitive basement membrane and by the cytoplasm of pericytes which are oriented spirally to the longitudinal axes of the vessels. The pericytes may have a function in the mechanical support of the vascular wall and a contractile function that might regulate the flow rate of blood.