Pathogenesis of Brain Edema and Hemorrhage: Role of the Brain Capillary

PEDIATRICS ◽  
1979 ◽  
Vol 64 (3) ◽  
pp. 357-360
Author(s):  
Gary W. Goldstein
Keyword(s):  
Endothelial Cells ◽  
Brain Edema ◽  
Tight Junctions ◽  
Interstitial Fluid ◽  
Water Soluble ◽  
Brain Capillaries ◽  
Reye's Syndrome ◽  
Anatomic Site ◽  
Brain Capillary ◽  
The Brain

It has recently been shown that the endothelial cells in brain capillaries are the anatomic site of the blood-brain barrier, and that these endothelial cells act to maintain a constant composition and volume of brain interstitial fluid.1-3 Defects in brain capillary function appear to play a role in the pathogenesis of brain edema and hemorrhage in a wide variety of diseases. Conditions as diverse as intraventricular hemorrhage of the premature, asphyxia neonatorum, lead poisoning, head injury, Reye's syndrome, osmolar coma, and the brain edema surrounding a tumor or abscess may all share the common feature of brain capillary failure. In this review, I will consider some recent advances in our understanding of the brain microvasculature that may explain their unusual susceptibility to injury. Brain capillaries have a number of important differences from capillaries in other organs. A schematic of a typical brain capillary is shown in the Figure. Unlike systemic capillaries, the endothelial cells in brain capillaries are joined together by tight junctions.3 These cellular junctions are present around the entire circumference of the capillary tube. The result is a continuous layer of endothelial cells that effectively separate the plasma from the interstitial fluid of the brain. The tight junctions are composed of a series of complex interdigitations that create a barrier so complete that water-soluble molecules and ions are unable to move into the brain between the endothelial cells. In other organs, the capillaries do not have tight junctions, and sugars, amino acids, ions, and drugs readily diffuse between endothelial cells into the interstitial fluid.

scholarly journals Age influences susceptibility of brain capillary endothelial cells to La Crosse virus infection and cell death

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Rahul Basu ◽  
Vinod Nair ◽  
Clayton W. Winkler ◽  
Tyson A. Woods ◽  
Iain D. C. Fraser ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Virus Infection ◽  
La Crosse Virus ◽  
Brain Capillary ◽  
Adult Mice ◽  
Age Related ◽  
Capillary Endothelial Cells ◽  
The Brain

Abstract Background A key factor in the development of viral encephalitis is a virus crossing the blood-brain barrier (BBB). We have previously shown that age-related susceptibility of mice to the La Crosse virus (LACV), the leading cause of pediatric arbovirus encephalitis in the USA, was associated with the ability of the virus to cross the BBB. LACV infection in weanling mice (aged around 3 weeks) results in vascular leakage in the olfactory bulb/tract (OB/OT) region of the brain, which is not observed in adult mice aged > 6–8 weeks. Thus, we studied age-specific differences in the response of brain capillary endothelial cells (BCECs) to LACV infection. Methods To examine mechanisms of LACV-induced BBB breakdown and infection of the CNS, we analyzed BCECs directly isolated from weanling and adult mice as well as established a model where these cells were infected in vitro and cultured for a short period to determine susceptibility to virus infection and cell death. Additionally, we utilized correlative light electron microscopy (CLEM) to examine whether changes in cell morphology and function were also observed in BCECs in vivo. Results BCECs from weanling, but not adult mice, had detectable infection after several days in culture when taken ex vivo from infected mice suggesting that these cells could be infected in vitro. Further analysis of BCECs from uninfected mice, infected in vitro, showed that weanling BCECs were more susceptible to virus infection than adult BCECs, with higher levels of infected cells, released virus as well as cytopathic effects (CPE) and cell death. Although direct LACV infection is not detected in the weanling BCECs, CLEM analysis of brain tissue from weanling mice indicated that LACV infection induced significant cerebrovascular damage which allowed virus-sized particles to enter the brain parenchyma. Conclusions These findings indicate that BCECs isolated from adult and weanling mice have differential viral load, infectivity, and susceptibility to LACV. These age-related differences in susceptibility may strongly influence LACV-induced BBB leakage and neurovascular damage allowing virus invasion of the CNS and the development of neurological disease.

Filtration Coefficient of the Capillaries of the Brain

1958 ◽  
Vol 195 (2) ◽  
pp. 459-464 ◽  
Author(s):  
N. A. Coulter
Keyword(s):  
Filtration Rate ◽  
Filtration Coefficient ◽  
Secretory Process ◽  
Brain Capillaries ◽  
Brain Capillary ◽  
Average Value ◽  
Capillary Membranes ◽  
The Brain ◽  
Muscle Capillaries

The Monro-Kellie doctrine was used as the basis for determination of the filtration coefficient of the capillaries of the cat's brain. An average value of 10.3 x 10–8 ml/sec/cm H2O/cm2 was found. A linear relation was observed between filtration rate and filtration pressure. The fact that the filtration coefficient of brain capillaries is somewhat higher than that of muscle capillaries suggests that lipoid insoluble molecules actually penetrate the brain capillary membranes readily, but are pumped back by a secretory process.

scholarly journals How Hormones Influence Composition and Physiological Function of the Brain-Blood Barrier

2015 ◽  
pp. S259-S264 ◽  
Author(s):  
R. HAMPL ◽  
M. BIČÍKOVÁ ◽  
L. SOSVOROVÁ
Keyword(s):  
Endothelial Cells ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Physiological Function ◽  
Brain Barrier ◽  
Major Protein ◽  
Other Substances ◽  
And Function ◽  
Protein Transporters ◽  
The Brain

Hormones exert many actions in the brain. Their access and effects in the brain are regulated by the blood-brain barrier (BBB). Hormones as other substances may enter the brain and vice versa either by paracellular way requiring breaching tight junctions stitching the endothelial cells composing the BBB, or by passage through the cells (transcellular way). Hormones influence both ways through their receptors, both membrane and intracellular, present on/in the BBB. In the review the main examples are outlined how hormones influence the expression and function of proteins forming the tight junctions, as well as how they regulate expression and function of major protein transporters mediating transport of various substances including hormone themselves.

MO002THE EXPRESSION OF AQUAPORINS IN A MOUSE CEREBRAL ISCHEMIC MODEL WITH MANNITOL EFFECTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yasuko Tanaka ◽  
Shin Koike ◽  
Kaho Kashima ◽  
Asuka Kaseda ◽  
Kenichi Ishibashi
Keyword(s):  
Body Weight ◽  
Brain Edema ◽  
Brain Infarction ◽  
Serum Osmolality ◽  
The Other ◽  
Brain Diseases ◽  
Brain Capillary ◽  
Cerebral Ischemic ◽  
The Brain

Abstract Background and Aims As the brain edema influences the outcomes of many edematous brain diseases due to the limited intracranial space, the role of aquaporins (AQPs) in brain edema needs to be clarified to advance its treatment especially in increasing ischemic brain diseases. Although the importance of AQP4 at the Blood Brain Barrier (BBB) has been well characterized, the roles of other AQPs is still unknown, especially a relatively new AQP11. As AQP11 is expressed in the brain capillary (Koike S et al. Int J Mol Sci. 17:861, 2016), AQP11 may also be important for the regulation of brain edema. The aim of the present study is to clarify the role of AQP11 in cerebral ischemic model to identify new treatment of cerebral edema. Method AQP expression in the brain was examined by RT-PCR. Common cervical artery was ligated for 15 min to produce ischemic-reperfusion model of brain infarction to induce brain edema. As the first step to study the involvement of AQPs in this process, the mRNA expression of AQP1, AQP4, AQP11 and GFAP were monitored after reperfusion which are expressed at BBB. As mannitol is often employed for the treatment of brain edema, the effects of single or twice doses of 1.1M mannitol 0.1 mL/g body weight i.p. on the expression of AQP1, AQP4 and AQP11 mRNA were examined after 6 h in control mice. Furthermore, hypertonic 2M NaCl was also challenged to simulate the osmotic effect: a single or twice doses of 2M NaCl 0.16 mL/g body weight were administered intraperitoneally, i.p. Results The expression of AQP1 mRNA increased by 20% one and two hours after 15-min ligation, while the expression of AQP4 mRNA decreased transiently just after the ligation but increased at 24 h by 10%. On the other hand, the expression of AQP11 mRNA started to decrease from 30 min after the ligation to continue decreasing up to 24h by 40% in wild mice, while the decrease of AQP11 mRNA only observed at 24h by 20% in AQP11 heterogenous KO mice. A single mannitol i.p. did not change serum osmolality from 320 to 317 mOsm, while twice i.p. in 6 h interval increased serum osmolality to 328 mOsm. Both procedures similarly decreased the expression of all AQPs: AQP1 by 80%, AQP4 by 40%, and AQP11 by 50%. Similar studies were conducted with 2M NaCl. A single dose of 2M NaCl increased serum Na/Osm from 151/319 to 154/322 mEq/mOsm, which decreased AQP1 by 50%, AQP11 by 35% and no change of AQP4. On the other hand, twice doses in 3 h interval increased serum Na/Osm to 208/435 mEq/Osm, which did not change all AQP expressions. Conclusion As AQP4 KO mice survive longer in brain edema models, decrease of AQP4 by mannitol will be beneficial as brain infarction increased AQP4 expression in our study. However, further decrease of AQP11 by mannitol will be detrimental as AQP11 was already decreased in brain infarction. As AQP11 KO mice die within a month due to polycystic kidneys, the studies on brain infarction in brain capillary specific AQP11 conditionaly KO mice are currently underway.

scholarly journals P-Glycoprotein-Mediated Transport of Itraconazole across the Blood-Brain Barrier

1998 ◽  
Vol 42 (7) ◽  
pp. 1738-1744 ◽  
Author(s):  
Tetsuo Miyama ◽  
Hitomi Takanaga ◽  
Hirotami Matsuo ◽  
Katsuhiro Yamano ◽  
Koujirou Yamamoto ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Half Life ◽  
Liver Tissue ◽  
Brain Barrier ◽  
Brain Capillary ◽  
P Glycoprotein ◽  
Capillary Endothelial Cells ◽  
The Brain

ABSTRACT The mechanism for the accumulation of itraconazole (ITZ) in its elimination from the brain was studied in rats and mice. The concentration of ITZ in liver tissue declined in parallel with the plasma ITZ concentration until 24 h after intravenous injection of the drug (half-life, 5 h); however, the ITZ in brain tissue rapidly disappeared (half-life, 0.4 h). The time profiles of the brain/plasma ITZ concentration ratio (Kp value) showed a marked overshooting, and the Kp value increased with increasing dose; these phenomena were not observed in the liver tissue. This finding indicates the occurrence of a nonlinear efflux of ITZ from the brain to the blood. Moreover, based on a pharmacokinetic model which hypothesized processes for both nonlinear and linear effluxes of ITZ from the brain to the blood, we found that the efflux rate constant in the saturable process was approximately sevenfold larger than that in the nonsaturable process. TheKp value for the brain tissue was significantly increased in the presence of ketoconazole or verapamil. The brainKp value for mdr1a knockout mice was also significantly increased compared with that of control mice. Moreover, the uptake of vincristine or vinblastine, both of which are substrates of the P glycoprotein (P-gp), into mouse brain capillary endothelial cells was also significantly increased by ITZ or verapamil. In conclusion, P-gp in the brain capillary endothelial cells participates in a process of active efflux of ITZ from the brain to the blood at the blood-brain barrier, and ITZ can be an inhibitor of various substrates of P-gp.

Hormones and the blood-brain barrier

2015 ◽  
Vol 21 (3) ◽  
Author(s):  
Richard Hampl ◽  
Marie Bičíková ◽  
Lucie Sosvorová
Keyword(s):  
Endothelial Cells ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Energy Homeostasis ◽  
Brain Structures ◽  
Brain Barrier ◽  
Selection Function ◽  
Membrane Structures ◽  
Blood Brain ◽  
The Brain

AbstractHormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

scholarly journals Efficient isolation of brain capillary from a single frozen mouse brain for protein expression analysis

2020 ◽  
pp. 0271678X2094144
Author(s):  
Seiryo Ogata ◽  
Shingo Ito ◽  
Takeshi Masuda ◽  
Sumio Ohtsuki
Keyword(s):  
Protein Expression ◽  
Mouse Brain ◽  
Expression Analysis ◽  
Brain Capillaries ◽  
Purification Step ◽  
Brain Capillary ◽  
Pathological Conditions ◽  
Protein Expressions ◽  
Isolation Methods ◽  
The Brain

Isolated brain capillaries are essential for analyzing the changes of protein expressions at the blood–brain barrier (BBB) under pathological conditions. The standard brain capillary isolation methods require the use of at least five mouse brains in order to obtain a sufficient amount and purity of brain capillaries. The purpose of this study was to establish a brain capillary isolation method from a single mouse brain for protein expression analysis. We successfully isolated brain capillaries from a single frozen mouse brain by using a bead homogenizer in the brain homogenization step and combination of cell strainers and glass beads in the purification step. Western blot and proteomic analysis showed that proteins expressed at the BBB in mouse brain capillaries isolated by the developed method were more enriched than those isolated from a pool of five mouse brains by the standard method. By using the developed method, we further verified the changes in expression of BBB proteins in Glut1-deficient mouse. The developed method is useful for the analysis of various mice models with low numbers and enables us to understand, in more detail, the physiology and pathology of BBB.

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