Astrocyte plasticity ensures continued endfoot coverage of cerebral blood vessels and integrity of the blood brain barrier, with plasticity declining with normal aging

2021 ◽  
Author(s):  
Ranabir Chakraborty
Keyword(s):  
Blood Vessels ◽  
Blood Brain Barrier ◽  
Normal Aging ◽  
Brain Barrier ◽  
Cerebral Blood Vessels ◽  
Blood Brain

Effects of endothelin and vasopressin on cerebral blood vessels

1989 ◽  
Vol 257 (3) ◽  
pp. H799-H803 ◽  
Author(s):  
F. M. Faraci
Keyword(s):  
Blood Vessels ◽  
Blood Brain Barrier ◽  
Basilar Artery ◽  
Brain Barrier ◽  
Fluorescein Sodium ◽  
Cerebral Blood Vessels ◽  
Blood Brain ◽  
Pial Arterioles ◽  
High Doses ◽  
The Brain

Endothelin is a recently described peptide which has been suggested to be one type of endothelium-derived contracting factor. The goals of the present study were to examine the effects of endothelin and vasopressin on diameter of cerebral vessels and on permeability of the blood-brain barrier to fluorescein sodium (mol wt of 376). In anesthetized rats, topical suffusion of arginine vasopressin (10(-10) to 10(-7) M) decreased the diameter of pial arterioles, with a reduction of 27 +/- 1% at 10(-7) M in cerebrum and 35 +/- 2% at 10(-8) M for the basilar artery. A low concentration of endothelin (10(-10) M) produced modest (5 +/- 1%) dilatation of pial arterioles. Higher concentrations of endothelin (10(-8) and 10(-7) M) constricted pial arterioles with a reduction in diameter of 22 +/- 5% at 10(-7) M. Dilatation to endothelin was not observed in the basilar artery. The basilar artery constricted to lower doses of vasopressin than endothelin, but vasoconstriction to 10(-7) M endothelin (56 +/- 4%) was greater (P less than 0.05) than that for the same dose of vasopressin. Permeability of the blood-brain barrier to fluorescein sodium was not increased by vasopressin or endothelin. Thus 1) vasopressin produces constriction of brain blood vessels; 2) endothelin produces dilatation of pial arterioles at low doses but constriction at high doses; 3) constrictor responses to both peptides appear to be greater in the brain stem than in the cerebrum; and 4) vasopressin and endothelin do not increase permeability of the blood-brain barrier.

scholarly journals PATH-04. THE BLOOD-BRAIN BARRIER IN DIFFUSE MIDLINE GLIOMA AND ITS IMPLICATIONS FOR DRUG DELIVERY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii164-ii164
Author(s):  
Rianne Haumann ◽  
Fatma El-Khouly ◽  
Marjolein Breur ◽  
Sophie Veldhuijzen van Zanten ◽  
Gertjan Kaspers ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Blood Vessels ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Vascular Density ◽  
Zonula Occludens ◽  
Blood Brain ◽  
Zonula Occludens 1 ◽  
End Stage ◽  
Diffuse Midline Glioma

Abstract INTRODUCTION Chemotherapy has been unsuccessful for pediatric diffuse midline glioma (DMG) most likely due to an intact blood-brain barrier (BBB). However, the BBB has not been characterized in DMG and therefore its implications for drug delivery are unknown. In this study we characterized the BBB in DMG patients and compared this to healthy controls. METHODS End-stage DMG pontine samples (n=5) were obtained from the VUmc diffuse intrinsic pontine glioma (DIPG) autopsy study and age-matched healthy pontine samples (n=22) were obtained from the NIH NeuroBioBank. Tissues were stained for BBB markers claudin-5, zonula occludens-1, laminin, and PDGFRβ. Claudin-5 stains were used to determine vascular density and diameter. RESULTS In DMG, expression of claudin-5 was reduced and dislocated to the abluminal side of endothelial cells. In addition, the expression of zonula occludens-1 was reduced. The basement membrane protein laminin expression was reduced at the glia limitans in both pre-existent vessels and neovascular proliferation. PDGFRβ expression was not observed in DMG but was present in healthy pons. Furthermore, the number of blood vessels in DMG was significantly (P< 0.01) reduced (13.9 ± 11.8/mm2) compared to healthy pons (26.3 ± 14.2/mm2). Markedly, the number of small blood vessels (< 10µm) was significantly lower (P< 0.01) while larger blood vessels (> 10µm) were not significantly different (P= 0.223). The mean vascular diameter was larger for DMG 9.3 ± 9.9µm compared to 7.7 ± 9.0µm for healthy pons (P= 0.016). CONCLUSION Both the BBB and the vasculature are altered at end-stage DMG. The reduced vascular density might have implications for several drug delivery methods such as focused ultrasound and convection enhanced delivery that are being explored for the treatment of DMG. The functional effects of the structurally altered BBB remain unknown and further research is needed to evaluate the BBB integrity at end-stage DMG

scholarly journals Immunolocalization of Heat Shock Protein after Fluid Percussive Brain Injury and Relationship to Breakdown of the Blood-Brain Barrier

1993 ◽  
Vol 13 (1) ◽  
pp. 116-124 ◽  
Author(s):  
Hirokazu Tanno ◽  
Russ P. Nockels ◽  
Lawrence H. Pitts ◽  
Linda J. Noble
Keyword(s):  
Brain Injury ◽  
Head Injury ◽  
Blood Vessels ◽  
Blood Brain Barrier ◽  
Time Course ◽  
Cortical Layer ◽  
Brain Barrier ◽  
Impact Site ◽  
Blood Brain ◽  
The Impact

We have previously developed a model of mild, lateral fluid percussive head injury in the rat and demonstrated that although this injury produced minimal hemorrhage, breakdown of the blood–brain barrier was a prominent feature. The relationship between posttraumatic blood–brain barrier disruption and cellular injury is unclear. In the present study we examined the distribution and time course of expression of the stress protein HSP72 after brain injury and compared these findings with the known pattern of breakdown of the blood–brain barrier after a similar injury. Rats were subjected to a lateral fluid percussive brain injury (4.8–5.2 atm, 20 ms) and killed at 1, 3, and 6 h and 1,3, and 7 days after injury. HSP72-like immunoreactivity was evaluated in sections of brain at the light-microscopic level. The earliest expression of HSP72 occurred at 3 h postinjury and was restricted to neurons and glia in the cortex surrounding a necrotic area at the impact site. By 6 h, light immunostaining was also noted in the pia-arachnoid adjacent to the impact site and in certain blood vessels that coursed through the area of necrosis. Maximal immunostaining was observed by 24 h postinjury, and was primarily associated with the cortex immediately adjacent to the region of necrosis at the impact site. This region consisted of darkly immunostained neurons, glia, and blood vessels. Immunostaining within the region of necrosis was restricted to blood vessels. HSP72-like immunoreactivity was also noted in a limited number of neurons and glia in other brain regions, including the parasagittal cortex, deep cortical layer VI, and CA3 in the posterior hippocampus. Immunoreactive cells in these areas were not apparent until 24 h postinjury. By 7 days postinjury, HSP72-like immunoreactivity was minimal or absent in these injured brains and notable cell loss was apparent only in the impact site. This study demonstrates an early and pronounced expression of HSP72 at the impact site and a more delayed and less prominent expression of this protein in other regions of the brain. These findings parallel the temporal and regional pattern of breakdown of the blood–brain barrier after a similar head injury.

scholarly journals Amyloid Efflux Transporter Expression at the Blood-Brain Barrier Declines in Normal Aging

2010 ◽  
Vol 69 (10) ◽  
pp. 1034-1043 ◽  
Author(s):  
Gerald D. Silverberg ◽  
Arthur A. Messier ◽  
Miles C. Miller ◽  
Jason T. Machan ◽  
Samir S. Majmudar ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Normal Aging ◽  
Brain Barrier ◽  
Efflux Transporter ◽  
Blood Brain ◽  
Transporter Expression

scholarly journals Kernicterus in an Adult Dog

2018 ◽  
Vol 46 ◽  
pp. 3
Author(s):  
Luciana Sonne ◽  
Djeison Lutier Raymundo ◽  
Bianca Santana De Cecco ◽  
Adriana Da Silva Santos ◽  
Caroline Argenta Pescador ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Blood Brain Barrier ◽  
Binding Capacity ◽  
Glutamate Uptake ◽  
Unconjugated Bilirubin ◽  
Brain Barrier ◽  
Neuronal Necrosis ◽  
Bilirubin Encephalopathy ◽  
Blood Brain ◽  
The Brain

Background: Kernicterus or bilirubin encephalopathy is a condition rarely observed in animal characterized by a yellowish discoloration of the central nervous system. It is a potentially fatal condition due to bilirubin neurotoxic effects caused by the increase of non-conjugated bilirubin pigment, which passes blood brain barrier and has been attributed to an imbalance between albumin and bilirubin levels. Intracellular bilirubin is toxic for cells and can cause decrease in protein synthesis, specially albumin, depression of cell respiration and cellular death. This paper describes kernicterus in a 2-year-old Great Dane female dog.Case: Clinically, the animal showed apathy, lethargy, weight loss and jaundice, which progressed to vomiting and neurological signs characterized by loss of consciousness and eventually coma. Blood parameters were within normal range, except for high levels of alanine aminotransferase (523 U/L), suggesting a liver lesion. The animal was submitted to euthanasia due to the poor prognosis, and at post-mortem examination it showed dehydration and severe jaundice, especially oral, vaginal and ocular mucosas, subcutaneous tissue and blood vessels intima surface. The liver had an accentuated lobular pattern, and the stomach mucosa was reddened. Multiple petechiae were observed in the epicardium, as well as icterus in the blood vessels of the heart. Furthermore, the brain and cerebellum cortex, thalamic region and nuclei region of brainstemshowed extensive icteric areas. Microscopically, the liver presented a mononuclear portal hepatitis, centrilobular necrosis and presence of yellowish pigments. The brain had neuronal necrosis, mild vacuolization of the white matter, perineuronal edema and Alzheimer type II astrocytes, while cerebellum showed Purkinje cells necrosis. Hepatic cooper measurement was within range values, and direct imunofluorescence for the detection of Leptospira sp. was negative.Discussion: Kernicterus pathogenesis has been extensively studied, as the condition is commonly seen in neonatal humans. Diagnosis is based on gross and microscopic lesions in brain, which are consistent with bilirubin encephalopathy caused by the necrosis and degeneration of neurons. This condition is related to cases of intense hyperbilirubinemia, which exceedsthe albumin binding capacity and, therefore, the excess of unconjugated bilirubin that can pass through the blood brain barrier. Liver disease causes deficient production of protein, especially albumin, decreasing the potential binding capacity to bilirubin, and consequently causing hyperbilirubinemia. In this case, the previously detected hepatic lesion suggested by liver enzymes increased, probably led to protein production dysfunction, causing hypoalbuminemia and hyperbilirubinemia. Unfortunately, albumin and bilirubin seric levels could not be measured. Decrease in albumin production along with the excess of unconjugated bilirubin caused the jaundice, and in cases like this one described, the blood brain barrieris compromised and the kernicterus occurs. Unconjugated bilirubin has negative effect in the glutamate uptake causing extracellular accumulation of it, which is consequently neurotoxic, causing necrosis and degeneration leading to a characteristic encephalopathy in animals with kernicterus. In this report, it was not possible to determine the primary hepatic disease, however this caused clinical neurotoxic disease, known as bilirubin encephalopathy.Keywords: kernicterus, icterus, dog.

scholarly journals Mild hypoxia triggers transient blood–brain barrier disruption: a fundamental protective role for microglia

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Sebok K. Halder ◽  
Richard Milner
Keyword(s):  
Spinal Cord ◽  
Blood Vessels ◽  
Blood Brain Barrier ◽  
Protective Role ◽  
Neurological Dysfunction ◽  
Brain Barrier ◽  
Vascular Leak ◽  
Vascular Integrity ◽  
Blood Brain ◽  
Mild Hypoxia

Abstract We recently demonstrated that when mice are exposed to chronic mild hypoxia (CMH, 8% O2), blood vessels in the spinal cord show transient vascular leak that is associated with clustering and activation of microglia around disrupted vessels. Importantly, microglial depletion profoundly increased hypoxia-induced vascular leak, implying that microglia play a critical role maintaining vascular integrity in the hypoxic spinal cord. The goal of the current study was to examine if microglia play a similar vasculo-protective function in the brain. Employing extravascular fibrinogen leak as an index of blood–brain barrier (BBB) disruption, we found that CMH provoked transient vascular leak in cerebral blood vessels that was associated with activation and aggregation of Mac-1-positive microglia around leaky vessels. Interestingly, CMH-induced vascular leak showed regional selectivity, being much more prevalent in the brainstem and olfactory bulb than the cerebral cortex and cerebellum. Pharmacological depletion of microglia with the colony stimulating factor-1 receptor inhibitor PLX5622, had no effect under normoxic conditions, but markedly increased hypoxia-induced cerebrovascular leak in all regions examined. As in the spinal cord, this was associated with endothelial induction of MECA-32, a marker of leaky CNS endothelium, and greater loss of endothelial tight junction proteins. Brain regions displaying the highest levels of hypoxic-induced vascular leak also showed the greatest levels of angiogenic remodeling, suggesting that transient BBB disruption may be an unwanted side-effect of hypoxic-induced angiogenic remodeling. As hypoxia is common to a multitude of human diseases including obstructive sleep apnea, lung disease, and age-related pulmonary, cardiac and cerebrovascular dysfunction, our findings have important translational implications. First, they point to a potential pathogenic role of chronic hypoxia in triggering BBB disruption and subsequent neurological dysfunction, and second, they demonstrate an important protective role for microglia in maintaining vascular integrity in the hypoxic brain.

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