Micro- and macrovascular changes as the direct cause of parenchymal destruction in congenital murine hydrocephalus (original) (raw)
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Role of the subcommissural organ in the pathogenesis of congenital hydrocephalus in the HTx rat
Cell and Tissue Research, 2013
The present investigation was designed to clarify the role of the subcommissural organ (SCO) in the pathogenesis of hydrocephalus occurring in the HTx rat. The brains of non-affected and hydrocephalic HTx rats from embryonic day 15 (E15) to postnatal day 10 (PN10) were processed for electron microscopy, lectin binding and immunocytochemistry by using a series of antibodies. Cerebrospinal fluid (CSF) samples of non-affected and hydrocephalic HTx rats were collected at PN1, PN7 and PN30 and analysed by one-and two-dimensional electrophoresis, immunoblotting and nanoLC-ESI-MS/MS. A distinct malformation of the SCO is present as early as E15. Since stenosis of the Sylvius aqueduct (SA) occurs at E18 and dilation of the lateral ventricles starts at E19, the malformation of the SCO clearly precedes the onset of hydrocephalus. In the affected rats, the cephalic and caudal thirds of the SCO showed high secretory activity with all methods used, whereas the middle third showed no signs of secretion. At E18, the middle non-secretory third of the SCO progressively fused with the ventral wall of SA, resulting in marked aqueduct stenosis and severe hydrocephalus. The abnormal development of the SCO resulted in the permanent absence of Reissner's fibre (RF) and led to changes in the protein composition of the CSF. Since the SCO is the source of a large mass of sialilated glycoproteins that form the RF and of those that remain CSF-soluble, we hypothesize that the absence of this large mass of negatively charged molecules from the SA domain results in SA stenosis and impairs the bulk flow of CSF through the aqueduct.
Acta Neuropathologica, 1991
Tx rat first develops in late gestation and causes death at 4-7 weeks. The effect of hydrocephalus on overall cortical dimensions and on five specific regions (frontal, sensory-motor, parietal, auditory and visual) has been studied by quantitative light microscopy at 10 and 30 days after birth. The lateral ventricle volumes in hydrocephalic rats were about 40x larger than controls and increased fourfold between 10 and 30 days. Cortical volume was reduced by a small amount at 10 days but was larger in hydrocephalics at 30 days. Thinning of the cortical mantle was severe with disruption of the laminar structure, particularly in the auditory and visual regions, where it was already present at 10 days. The density of cortical cells (neurones and glia) was not altered in hydrocephalics at 10 days but was reduced in all regions at 30 days. Estimates of total cell number suggest that the lower density was not associated with an overall loss of cells. Capillary numerical density was not affected by the hydrocephalus at 10 days after birth but by 30 days it was significantly lower, particularly in the worst-affected posterior regions. The results show that the cerebral cortex is severely distorted and that in advanced hydrocephalus, although overall cell number is not affected, both cell density and capillary density are lower by up to 3O%.
Spontaneous Congenital Hydrocephalus in Sprague Dawley Rat
2014
Hydrocephalus is a neurological disorder that results from the accumulation of excess cerebrospinal fluid in the ventricles of the brain culminating in an enlarged cranium. This sporadic disorder may occur as a congenital malformation in many mammalian species including inbred rodent colonies at an early juvenile stage of life. Under conventional husbandry practice of breeding, 5 pups showing some clinical signs of neurological dysfunction at the age of 20 days were examined thoroughly. Detailed macroscopic examination demonstrated dome shaped head, thinned and deformed parietal bone, open/closed suture depending upon the severity of ventricular dilatation. Microscopic examination revealed dilated lateral ventricles, compressed and attenuated cortical mantle, spongy appearance of the sub-ventricular zone, stretched ventricular ependyma, flattened ependymal cell lining and infiltration of mononuclear cells in the ventricular lining.
Cerebrovascular Adaptation in Chronic Hydrocephalus
Journal of Cerebral Blood Flow & Metabolism, 2001
This study characterizes the regional changes in vascularity, which accompanies chronic progressive hydrocephalus. Fifteen dogs underwent surgical induction of hydrocephalus and were used for histologic studies. Animals were divided into 4 groups: surgical control, short term (≤5 weeks), intermediate term ((8 weeks), and long term (10 to 12 weeks). Vessel diameter, density, and luminal area were calculated by imaging quantification after manual vessel identification in the cortical gray, white matter, and caudate nucleus. Capillary vessel diameter decreased 23.5% to 30.2% ( P < 0.01) in the caudate, but then returned to normal at 12 weeks. Capillary vessel density decreased 53.5% ( P < 0.05) in the cortical gray, but then increased to 234.8% ( P < 0.01) over surgical controls at 12 weeks. There was no initial decrease in capillary density in the caudate; however, the long-term group capillary density was significantly greater (172.8% to 210.5%, P < 0.01) than surgical co...
Folia Neuropathologica Association of Polish Neuropathologists and Medical Research Centre Polish Academy of Sciences, 2009
Cortical biopsies of 13 patients with clinical diagnosis of congenital hydrocephalus, Arnold-Chiari malformation and hydrocephalus, and postmeningitis hydrocephalus were examined by transmission electron microscopy to study the damage of endothelial cells, basement membrane, astrocytic end-feet layer, and perivascular space. Capillaries from the parietal and frontal cortex showed increased vesicular and vacuolar transport, intact endothelial junctions, thin and immature basement membrane, swollen perivascular astrocytic end-feet layer, and enlarged perivascular space. In areas of severe oedema, open endothelial junctions, swollen basement membrane, absent perivascular astrocytic end-feet layer, enlarged perivascular space, and disrupted perivascular neuropil were observed. The electron microscopic findings demonstrated breakdown of the blood-brain barrier in all cases examined.
Journal of Neuroscience Methods, 1985
Key words: CNS microcirculation -cerebral vasculature -brain capillary -central nervous systemhorseradish peroxidase -light and electron microscopy A new method is described for morphological studies of blood vessels and related cellular elements in the mammalian central nervous system (CNS). The tracer protein, horseradish peroxidase (HRP), in solution, is infused intraventricularly or intracisternally in anesthetized animals over 5-10 min. During this period, HRP in the subarachnoid space enters the perivascular spaces around penetrating arterioles and rapidly permeates the giiovascular basal laminae surrounding capillaries. After fixation by intravascular perfusion of aldehydes, brain sections are incubated with the highly sensitive chromogen, tetramethylbenzidine. Intraparenchymal blood vessels throughout the CNS are vividly demonstrated for light microscopy by HRP reaction product in their perivascular spaces or basal laminae. Correlative ultrastructural investigations of specific blood vessels and related parenchymal elements can be conducted using adjacent sections.
SCO-ping Out the Mechanisms Underlying the Etiology of Hydrocephalus
Physiology, 2009
The heterogeneous nature of congenital hydrocephalus has hampered our understanding of the molecular basis of this common clinical problem. However, disease gene identification and characterization of multiple transgenic mouse models has highlighted the importance of the subcommissural organ (SCO) and the ventricular ependymal (vel) cells. Here, we review how altered development and function of the SCO and vel cells contributes to hydrocephalus.
Ependymal changes in experimental hydrocephalus
The Anatomical record, 1979
A morphologic investigation of ependyma over gray matter (caudate nucleus) and over periventricular white matter (tapetum) of the rabbit lateral ventricle was performed four months after the induction of experimental hydrocephalus. Ependymal cells over the caudate nucleus are not modified by hydrocephalus. They remain cuboidal and heavily ciliated. Numerous microvilli cover the cell surface. The extracellular space of the neuropil is not expanded. Ependymal cells over the periventricular white matter are markedly modified. The characteristic response of these ependymal cells is to enlarge and to form lacunae in their apical cytoplasm. Their apical, horizontal cytoplasmic processes elongate as adjacent ependymal cells separate. The extracellular space of the neuropil is expanded.
Review article Submicroscopic pathology of human and experimental hydrocephalic cerebral cortex
Folia Neuropathologica, 2010
The ultrastructural pathology of cerebral cortex in human hydrocephalus is reviewed and compared with experimental hydrocephalus. Nerve cells show moderate and severe swelling. The neighboring neuropil exhibits notable enlargement of extracellular space, synaptic plasticity and degeneration, damage of myelinated axons, and myelination delay. The astrocytes display edematous changes and phagocytic activity. Glycogen rich-and glycogen-depleted astrocytes are observed. Some oligodendroglial cells exhibit normal morphology, and other exhibit hydropic changes. The capillary wall shows signs of blood-brain barrier dysfunction. The role of ischemia, oxidative stress, increased calcium concentration, activation of NMDA receptors, and disturbance of ion homeostasis are discussed in relationship with the fine structural alterations of hydrocephalic brain parenchyma.