New ultrastructural evidence for a protein transport system in endothelial cells of gerbil brains

Lossinsky, A. S.; García, Julio Herrero; Iwanowski, L; Lightfoote, Johnson B.

doi:10.1007/bf00717032

Cited by 58 publications

(11 citation statements)

References 21 publications

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“…The cerebral endothelial cells from mice coinjected with dimethyl sulfoxide and peroxidase exhibit a proliferation ofperoxidase-labeled tubules, vesicles, and vacuoles when compared to control mice not receiving dimethyl sulfoxide. A similar proliferation of these peroxidase-labeled structures has been reported by other investigators after damage to the blood-brain barrier (27,28); these authors have proposed that the tubules function as transendothelial channels whereby direct communication is established between the vessel lumen and the perivascular space. This interpretation is highly speculative, because the tubules have yet to be seen interconnecting the luminal and abluminal walls of the endothelial cell.…”

Section: Resultssupporting

confidence: 83%

Expanding the definition of the blood-brain barrier to protein.

Broadwell¹,

Salcman²

1981

Proc. Natl. Acad. Sci. U.S.A.

114

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Tight junctions between cerebral endothelial cells and the near absence of pinocytosis and vesicular transport of blood-borne protein into and across these cells are believed to constitute the mammalian blood-brain barrier. In the present investigation evidence is provided to indicate that the capillary endothelium of the mouse brain pinocytoses the enzymatic tracer horseradish peroxidase (EC 1.11.1.17) from cerebral blood under normal conditions. This protein and the internalized endothelial surface membrane associated with it are directed, for the most part, to acid hydrolase-positive lysosomes for degradation. Although peroxidase was never seen in the perivascular clefts, the lysosomes of pericytes were peroxidase-positive. Pericytes are macrophage-like cells located on the abluminal surfaces of cerebral microvasculature; these cells may serve as the first line of defense once the blood-brain barrier is breached. The definition of the blood-brain barrier should be expanded to include consideration of the lysosomal system of organelles in endothelial cells and pericytes.Exogenous proteins and serum proteins are excluded from the cerebral extracellular fluid in mammals by the blood-brain barrier. Studies employing the enzymatic tracers horseradish peroxidase (EC 1.11.1.17; hereafter referred to as "peroxidase") and microperoxidase have led to attribution of the blood-brain barrier to two morphological characteristics of cerebral microvascular endothelial cells: circumferential belts of tight junctions between contiguous endothelial cells and the apparent absence of vesicular transport of blood-borne protein from the luminal to the abluminal face ofthe endothelium (1-4). In these studies, peroxidase-labeled vesicles were particularly rare in capillary endothelial cells, suggesting that, unlike capillaries supplying cardiac and striated muscles (5, 6), those in brain were not actively engaged in pinocytosis to an appreciable degree; however, one of these investigations (4) revealed that in the mouse an insignificant amount ofperoxidase did cross segments ofcertain cerebral arterioles to reach the perivascular basement membrane,-perhaps by vesicular transport. This paper will present evidence to suggest that pinocytosis of blood-borne peroxidase does indeed occur normally in cerebral capillaries. Emphasis is placed on pericytes and the lysosomal system within capillary endothelial cells as additional functional components of the blood-brain barrier. The acid hydrolase activities ofacid phosphatase (EC 3.1.3.2) (7, 8) and trimetaphosphatase (EC 3.6.1.2) (9) have been used as markers for lysosomes. MATERIALS AND METHODSTwenty-six young adult female white mice weighing 25-30 g were used. Eighteen mice received one, two, or three injections of 30 mg of horseradish peroxidase (type VI, Sigma) in 0.25-0.5 ml of 0.9% saline solution per injection into the tail vein. The desired length of the postinjection survival time determined the number of injections each mouse received. Survival times for these mice ranged ...

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Section: Resultssupporting

confidence: 83%

Expanding the definition of the blood-brain barrier to protein.

Broadwell¹,

Salcman²

1981

Proc. Natl. Acad. Sci. U.S.A.

114

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“…Furthermore, there is evidence that injection of air results in immediate breakdown of the blood-brain barrier. 29 In our model, embolization of atherosclerotic material could be excluded. None of the animals showed signs of atherosclerosis at organ removal.…”

Section: Discussionmentioning

confidence: 99%

Emboli Formation Rather Than Inflammatory Mediators Are Responsible for Increased Cerebral Water Content After Conventional and Assisted Beating-Heart Myocardial Revascularization in a Porcine Model

Bierbach¹,

Meier²,

Kasper-König³

et al. 2008

Stroke

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Background and Purpose-Emboli and proinflammatory mediators are suspected of generating cerebral edema after coronary surgery. In contrast to cardiopulmonary bypass (CPB), off-pump coronary artery bypass surgery (OPCAB) reduces microemboli count and proinflammatory mediator release but carries the risk of hemodynamic instability. A microaxial blood pump can augment cardiac output. Methods-Coronary bypasses were constructed in pigs with CPB and cardioplegia (nϭ9), OPCAB (nϭ9), or blood-pump support CAB (nϭ9). Nine animals underwent sham operation. Embolus count was monitored and regional cerebral blood flow was assessed with microspheres in 21 brain specimens per animal (nϭ189 per group). Interleukins 6 and 8 and tumor necrosis factor-␣ concentrations were determined. These variables were studied before, during, and for 4 hours after surgery. Finally, cerebral water content was determined. Results-During CPB and blood-pump CAB, a significant number of emboli were counted in contrast to OPCAB and controls (PϽ0.05). During CPB, regional cerebral blood flow was affected (32 of 189) and showed reactive hyperemia except in 10 specimens after aortic cross-clamp release. This impairment persisted in 20 specimens. During and after OPCAB, regional cerebral blood flow remained nearly unchanged but showed low flow during (58 of 189) and after (35 of 189) the blood-pump run. A significant increase in proinflammatory mediators was observed only in the CPB group. CPB and blood-pump CAB significantly increased cerebral water content (PϽ0.05). A strong correlation between embolic load and cerebral water content was observed in all groups. No correlation between proinflammatory mediator release and cerebral water content was detected. Conclusions-Emboli formation rather than inflammatory mediators are responsible for increased cerebral water content after conventional and assisted beating-heart myocardial revascularization. (Stroke. 2008;39:213-219.)

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“…19 Our study, however, failed to show either exudation of Evans blue dye or an increase in passage of 131 I-albumin during the period of 3 hrs ischemia. Likewise, Lossinsky et al, 17 Ito et al, 14 -20 and Schuier and Hoss mann 15 have found that BBB is intact during the period of 2, 4, and 9 hrs ischemia, indicating that protein extravasations hardly occur in complete cerebral ische mia because of zero blood flow. Our ischemic animal, however, should be called as model of incomplete ischemia since blood flow to the cortex or thalamus never reduced to zero level.…”

Section: Thalamusmidbrainmentioning

confidence: 99%

“…Under physiological condi tions, transendothelial migration of plasma protein in the brain is restricted by the presence of tight junctions and absence of appreciable vesicular transport. 16 Meanwhile, the electron microscopic studies on is chemic brain showed an increase in number of pinocytotic vesicles 3 or channel-like structures 17 in endotheli al cells using horseradish peroxidase technique. Increased permeability to macromolecules is referred as disruption of BBB.…”

Section: Thalamusmidbrainmentioning

confidence: 99%

Disruption of blood-brain barrier following bilateral carotid artery occlusion in spontaneously hypertensive rats. A quantitative study.

Sadoshima¹,

Fujishima²,

Ogata³

et al. 1983

Stroke

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SUMMARY The present study was designed to clarify the relationship of cerebral blood flow (CBF) to blood-brain barrier (BBB) in the ischemic brains with or without recirculation, which were produced by clipping of both common carotid arteries in spontaneously hypertensive rats. CBF was measured by the hydrogen clearance method and BBB function was evaluated by the permeability of I31 I-albumin and Evans blue dye.Cortical CBF was reduced from 48.8 ± 9.5 to 4.0 ± 1.2 ml/100 gm/min during 1 hr ischemia and further to 2.6 ± 0.3 ml/100 gm/min during 3 hrs ischemia, while thalamic CBF was reduced much less from 50.0 ± 3.6 to 17.9 ± 6.5 ml/100 gm/min and to 17.5 ± 11.0 ml/100 gm/min, respectively. There was no increase in permeability to protein tracers observed in such 1 hr or 3 hrs ischemic brain.Both cortical and thalamic CBF were markedly increased 2.5 to 6 fold of resting values at 5 min after recirculation in the 1 hr ischemic brain. In the 3 hrs ischemic brain, however, both CBF were only slightly increased but never restored to the resting level even at 30 min after recirculation. In such reperfused brains, exudation to Evans blue dye was observed in none of 16 animals with 1 hr ischemia, but in 18 of 23 with 3 hrs ischemia. Disruption of BBB was twice more frequent in the cortex (77.8%) than in either thalamus (33.3%) or hippocampus (33.3%). Permeability index of l31 I-albumin (brain albumin/blood albumin) was significantly higher in the ischemic areas stained with blue dye (2.07 ± 0.45%) than in non ischemic control brain (0.10 ± 0.01%).It was concluded that disruption of BBB was not evident until the brain was reperfused after ischemia. The critical level of CBF and its duration to induce postischemic edema were approximately 17 ml/100 gm/ min and 3 hrs, respectively. Stroke Vol 14, No 6, 1983ISCHEMIC BRAIN EDEMA is a major cause of death in patients with acute cerebral infarction. 1Such edema is primarily due to abnormal accumulation of fluid in and around the ischemic lesions, although its mecha nism is still under discussion. Recent advances in mi crosurgical techniques have generated interest in intra cranial reconstructive surgery. However, surgical treatment of ischemic strokes is both challenging and controversial. One of the reasons for its unsatisfactory outcome is assumed to be the result of widening de struction from the original infarct and of increased edema associated with secondary hemorrhage, known as hemorrhagic infarct, in some cases. There might be a critical period of ischemia which causes rather seri ous edema after restoration of blood flow. 2-4Previously we reported that spontaneously hyper tensive rats (SHR) developed cerebral ischemia by bi lateral occlusion of common carotid arteries. 5-8Bio chemical and morphological studies of the ischemic brains have shown the metabolic derangements such as anaerobic glycolysis and impaired energy metabo lism, 7 and pathological changes quite similar to those in humans. 6 In the present study, we examined changes in permeability to Evans blue dye...

show abstract

New ultrastructural evidence for a protein transport system in endothelial cells of gerbil brains

Cited by 58 publications

References 21 publications

Expanding the definition of the blood-brain barrier to protein.

Expanding the definition of the blood-brain barrier to protein.

Emboli Formation Rather Than Inflammatory Mediators Are Responsible for Increased Cerebral Water Content After Conventional and Assisted Beating-Heart Myocardial Revascularization in a Porcine Model

Disruption of blood-brain barrier following bilateral carotid artery occlusion in spontaneously hypertensive rats. A quantitative study.

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