ISSN:1059-910X    

DOI:10.1002/jemt.1070270602

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractDevelopment of a blood‐brain barrier (BBB) within mammalian CNS grafts, placed either intracerebrally or peripherally, has been controversial. Published data from this laboratory have emphasized the presence or the absence of a BBB within solid mammalian tissue or cell suspension grafts is determined intrinsically by the graft and not by the surrounding host parenchyma (e.g., brain, kidney, testis, etc.). Nevertheless, correctly interpreting whether or not a BBB exists within brain grafts is manifested by methodologies employed to answer the question and by ensuing neuropathological and immunological consequences of intracerebral grafting. The present study addresses these issues and suggests misinterpretation for the absence of a BBB in brain grafts can be attributed to: (1) rupture of interendothelial tight junctional complexes in vessels of CNS grafts fixed by perfusion of the host; (2) damage to host vessels and BBB during the intracerebral grafting procedure; (3) graft placement in proximity to inherently permeable vessels (e.g., CNS sites lying outside the BBB) supplying the subarachnoid space/pial surface and circumventricular organs such as the median eminence, area postrema, and choroid plexus; and (4) graft rejection associated with antigen presenting cells and the host immune response. The latter is prevalent in xenogeneic grafts and exists in allogeneic grafts with donor‐host mismatch in the major and/or minor histocompatibility complex. CNS grafts between non‐immunosuppressed outbred donor and host rats of the same strain (e.g., Sprague Dawley or Wistar rats) can be rejected by the host; these grafts exhibit populations of immuonohistochemically identifiable major histopatibility complex class I+ and class II+ cells (microglia, macrophages, etc.) and CD4+ T‐helper and CD8+ T‐cytotoxic lymphocytes. PC12 cell suspension grafts placed within the CNS of non‐immunosuppressed Sprague Dawley rats are rejected similarly. Donor cells from solid CNS grafts placed intracerebrally and stained immunohistochemically for donor major histocompatibility complex (MHC) class I expression are identified within the host spleen and lymph nodes; these donor MHC expressing cells may initiate the host immune response subsequent to the cells entering the general circulation through host cerebral vessels damaged during graft placement. Rapid healing of damaged cerebral vessels is stimulated with exogenously applied basic fibroblast growth factor, which may prove helpful in reducing the potential entry of donor cells to the host circulation. These results have implication clinically for the intracerebral grafting of human fetal CNS cell suspensions. © 1994 Wil

ISSN:1059-910X    

DOI:10.1002/jemt.1070270603

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe blood‐brain barrier is responsible for the maintenance of the neuronal microenvironment. This is accomplished by isolation of the brain from the blood by the tight junctions that join endothelial cells in cerebral microvessels, and by selective transport and metabolism of substances from blood or brain by the endothelial cells. This review describes the growth and maturation of the brain vasculature, and the development of the special properties of the endothelia at the blood‐brain interface. Evidence suggests that the development of the unique properties of the brain microvasculature is a consequence of tissue‐specific interactions between endothelial cells of extraneural origin and developing brain cells. The cellular and molecular mechanisms that control these processes are as yet unknown but this review will include experimental studies which have used in vivo and in vitro systems to investigate what factors may be involved, and some pathological conditions in which abnormal barrier development is thought to be an important aspect of the disease process. © 1994 Wiley‐L

ISSN:1059-910X    

DOI:10.1002/jemt.1070270604

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractRecent advances in our knowledge of the blood‐brain barrier have in part been made by studying the properties and function of cerebral endothelial cells in vitro. After an era of working with a fraction, enriched in cerebral microvessels by centrifugation, the next generation of in vitro blood‐brain barrier model systems was introduced, when the conditions for routinely culturing the endothelial cells were established. This review summarizes the results obtained mainly from this in vitro approach. Different elements of the intracellular signaling messenger systems have been detected in the course of our studies in the cerebral endothelial cells. It has been shown that the synthesizing enzymes of and substrate proteins for the second messenger molecules are present in the cerebral endothelial cells, and their activity and/or amount can change in pathological circumstances, i.e., during the formation of brain oedema. Pharmacological treatments interfering with the second messenger systems proved to be effective in the prevention of brain oedema formation. © 1994 Wiley‐Lis

ISSN:1059-910X    

DOI:10.1002/jemt.1070270605

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThis paper describes a quantitative approach to evaluating the ultrastructural features of brain capillaries that relate to the low non‐specific permeability of the blood‐brain barrier (BBB). Critical features in this approach include examination of large numbers of tissue samples and consistent, objective means of measuring features of interest. Junctional clefts, i.e., continuous channels between tight junctional regions correlate well with the know vascular permeability, being low in normal adult blood‐brain barrier, high in fetal brain, and high in tumours, both human and rat. Endothelial vesicles do not always correlate with vascular permeability. They have a low density in normal adult BBB, but are also low in fetal BBB and low in some intracranial tumour vessels. However, they have a high density in muscle capillaries, and others have shown that they increase in BBB vessels damaged by hypertension. Fenestrations are consistently high in leaky vessels, but not all leaky vessels have fenestrations. The density of mitochondria in endothelial cells is high in BBB vessels of some species but not in others. Glut‐1, the glucose transporter of the BBB is asymmetrically distributed between the luminal and abluminal membranes of BBB capillaries, being almost four times as numerous on the abluminal face. A large intracellular pool of glucose transporter may provide a means for rapid upregulation of the surface transporters. © 1994 Wiley

ISSN:1059-910X    

DOI:10.1002/jemt.1070270606

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractWe have previously reported that exposure of rats to low‐field (0.15 T) magnetic resonance imaging (MRI) increases blood‐brain barrier (BBB) permeability. However, a number of investigators have failed to observe this effect when high‐field MRI (1.5 T or higher) is used. Therefore, we investigated whether or not we would observe changes using our technique at these higher fields.Adult male Sprague‐Dawley rats were anaesthetised and then exposed to a 22.5 min imaging or sham procedure. Immediately following exposure, rats were injected with 1 MBq of153Gd‐DTPA intracardially and then immediately re‐exposed for an additional 22.5 min. The rats were killed 1h following the second MRI exposure, at which time the brain was resected and 3ml of venous blood collected. The ratio of radioactivity per gram of brain to radioactivity per per milliliter of blood, known as the brain‐blood partition coefficient, was determined and used as a measure of BBB permeability. Groups of animals had different exposures. Group 1 (n = 9) was exposed to a clinically relevant MRI procedure. Group 2 (n = 20) was exposed to the same procedure except the rf specific absorption rate (SAR) was reduced to 25% and the animals were positioned 15 cm from imager centre to increase the time‐varying magnetic field from 0.4 to 2.8 T/s. For the sham exposures (n = 21), the animals were placed in the imager with the static field ramped down to zero and exposed to a sound recording simulating a MRI examination. In a third group (n = 11), exposure to only the static 1.5 T was investigated, while in a fourth group (n = 15), the exposure field was only to a static 1.89 T. Sham controls for groups 3 (n = 12) and 4 (n = 19) were silent.Group 1 showed an increase in BBB permeability (5.7 ± 0.5, mean ± SEM,P<0.04, n = 9); however, group 2 showed a decrease (3.9 ± 0.2,P<0.002, n = 20). Static field exposure of 1.5 T increased permeability (5.7 ± 0.5,P<0.05, n = 11) as did 1.89 T (4.7 ± 0.4,P<0.02, n = 15). Although there was no difference between sound and silent shams, shams done at night (4.8 ± 0.2, n = 32) were significantly greater (P<0.0004) than those done during the day (3.7 ± 0.2, n = 19). Our results suggest changes in the rf and/or gradient field exposure can produce opposite effects on BBB permeability. Further, experiments involving only rf and only gradient field exposure are needed.The estimation of changes in BBB permeability by measuring the partition coefficient of compounds normally excluded by the BBB offers an objective quantitative technique which can detect changes of the order of 25%. This sensitivity is needed to explore the important, albeit subtle, effects of magnetic fields.

ISSN:1059-910X    

DOI:10.1002/jemt.1070270607

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractBiological effects of electromagnetic fields (EMF) on the blood‐brain barrier (BBB) can be studied in sensitive and specific models. In a previous investigation of the permeability of the blood‐brain barrier after exposure to the various EMF‐components of proton magnetic resonance imaging (MRI), we found that the exposure to MRI induced leakage of Evans Blue labeled proteins normally not passing the BBB of rats [Salford et al. (1992), in:Resonance Phenomena in Biology, Oxford University Press, pp. 87–91].In the present investigation we exposed male and female Fischer 344 rats in a transverse electromagnetic transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse‐modulated with repetition rates of 8, 16, 50, and 200 s−1. The specific energy absorption rate (SAR) varied between 0.016 and 5 W/kg.The rats were not anesthetized during the 2‐hour exposure. All animals were sacrificed by perfusion‐fixation of the brains under chloral hydrate anesthesia about 1 hour after the exposure. The brains were perfused with saline for 3–4 minutes, and thereafter fixed in 4% formaldehyde for 5–6 minutes. Central coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 μm. Albumin and fibrinogen were demonstrated immunohistochemically.The results show albumin leakage in 5 of 62 of the controls and in 56 of 184 of the animals exposed to 915 MHz microwaves. Continuous wave resulted in 14 positive findings of 35, which differ significantly from the controls (P= 0.002). With pulsed 915 MHz microwaves with repetition rates of 200, 50, 16, and 8 s−1, 42 of 149 were positive, which is highly significant at theP= 0.001 level. This reveals that both CW and pulsed 915 MHz microwaves have the potential to open up the BBB for albumin passage. However, there is no significant difference between continuous and pulsed 915 MHz microwaves in this respect.The frequency of occurrence of extravasates (26%) was found to be independent of SAR for SAR<2.5 W/kg, but rose significantly for the higher SAR values (to 43%).The question of whether the opening of the blood‐brain barrier constitutes a health hazard demands further investigation

ISSN:1059-910X    

DOI:10.1002/jemt.1070270608

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

摘要:

AbstractThe anatomical site of the blood‐brain barrier (BBB) is at the capillary endothelium mainly, with some contribution from astrocytes. Electron microscopic observations of endothelial cells and perivascular astrocytes comprising the BBB in brain edema and other pathological conditions are reviewed in this article. The tight junctions of cerebral endothelial cells open under several conditions such as infusion of hyperosmolar solutions. Pinocytotic vesicles increase under various pathological conditions and fenestrae appear in blood vessels of certain brain tumors and several non‐neoplastic lesions. Inflammatory cells penetrate between or through endothelial cells. In long standing lesions, endothelial cells containing various tubular structures such as Weibel‐Palade bodies proliferate. Other alterations include surface infoldings of endothelial cells and fluid diffusion through damaged endothelium. Astrocytic alterations include abnormal junctions between astrocytic processes in certain gliomas. In vivo and in vitro studies suggest that astrocytes maintain or develop certain functions of BBB. As the BBB is disrupted, edema fluid infiltrates the brain parenchyma. Because the white matter consists of nerve fibers without demonstrable junctions, it invades between nerve fibers. In the gray matter, expansion of the fluid is limited by complicated anatomical structures. In myelinated nerve fibers, edema fluid accumulates in five separate compartments of extracellular space. © 1994 Wiley‐L

ISSN:1059-910X    

DOI:10.1002/jemt.1070270609

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:1059-910X    

DOI:10.1002/jemt.1070270610

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY

ISSN:1059-910X    

DOI:10.1002/jemt.1070270601

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1994

数据来源: WILEY