SEARCH · PubMed Health

Results for “Microvessels”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed1998

Hepatocyte growth factor/scatter factor and its receptor c-Met are overexpressed and associated with an increased microvessel density in malignant pleural mesothelioma.

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates cell proliferation, motility and invasiveness via its receptor c-Met during embryogenesis and repair processes. It induces angiogenesis, promoting endothelial cell migration and capillary-tube formation in vivo. Co-expression of HGF/SF and c-Met receptor results in enhanced tumour growth, invasiveness and a mesenchymal-epithelial transition in some experimental tumours. Since mesothelioma cells have been reported to express c-Met receptor and to migrate in response to HGF/SF, we investigated human malignant pleural mesotheliomas for the demonstration of possible co-expression of the growth factor and its receptor. The microvessel density of the tumours was also analysed in order to assess the influence of HGF/SF expression on tumour angiogenesis. Thirty-nine paraffin-embedded specimens of malignant pleural mesotheliomas were immunostained by anti-HGF/SF and anti-c-Met antibodies and semiquantitatively evaluated. c-Met mRNA expression was visualised in ten tumour samples by a fluorescent in situ hybridisation method. Microvessel density was calculated by counting microvessels with a high-power field (200x) on von-Willebrand-factor-stained slides. We found an increased production of HGF/SF in 33/39 tumours and a corresponding overexpression of c-Met receptor in 29/39 specimens. The FISH method detected increased transcription of c-Met mRNA in malignant cells and in neighbouring vascular endothelial cells. HGF/SF-positive mesotheliomas had significantly higher microvessel densities compared to their HGF/SF-negative counterparts. The observed co-expression of HGF/SF and c-Met in malignant pleural mesotheliomas suggests a possible self-stimulation (autocrine loop) of tumour cells. On the basis of the significantly higher microvessel density values of malignant mesotheliomas overexpressing HGF/SF, we postulate, that HGF/SF may be an additional relevant factor in tumour angiogenesis in malignant pleural mesotheliomas.

Hepatocyte Growth Factor↗

PubMed1992

Transferrin receptors of rat and human brain and cerebral microvessels and their status in Alzheimer's disease.

We studied the regional distribution of specific [125I]transferrin binding to transferrin receptors in the brains and cerebral microvessels of humans and rats. We also assessed transferrin receptors in subjects with Alzheimer's disease. Human diferric [125I]transferrin bound to regional brain and cerebral microvessels with high affinity (dissociation constants of 1-10 nM), and the maximal binding densities ranged from 30 to 90 pmol/mg protein in the brain and were several-fold higher in cerebral microvessels. In Alzheimer's disease, transferrin receptor densities were significantly reduced in the hippocampus and the temporal and occipital cortex but were unchanged in the frontal and parietal cortex and the cerebellum. Although [125I]transferrin binding was higher in cerebral microvessels from subjects with Alzheimer's disease than in those of age-matched controls, this difference did not attain statistical significance. These results suggest that transferrin receptor density was decreased in some cortical areas including the hippocampus in Alzheimer's disease but relatively unchanged in cerebral microvessels.

Alzheimer Disease↗

PubMed1993

Localization of immunoreactive glutamyl aminopeptidase in rat brain. I. Association with cerebral microvessels.

Glutamyl aminopeptidase (aminopeptidase-A, EC 3.4.11.7) is an ectoenzyme that selectively hydrolyses N-terminal glutamyl and aspartyl residues from oligopeptides, including (Asp1) angiotensin II. Here we sought to determine the distribution of glutamyl aminopeptidase (EAP) in rat brain. EAP was purified to homogeneity from rat kidney and polyclonal antiserum raised in rabbits. Immune serum inhibited EAP enzyme activity in kidney homogenates and labeled two major protein bands of M(r) = 136,000 and M(r) = 101,000 in immunoblots of kidney protein. EAP-like immunoreactivity was concentrated on kidney proximal tubule brush borders. Immunocytochemical staining of rat brain indicated that EAP-like immunoreactivity was primarily associated with cerebral microvessels. Positive staining was detected in microvessels ranging in size from capillaries up to vessels approximately 50 microns in diameter. Isolated cerebral microvessels had a 23-fold enrichment in EAP enzyme activity (193.1 +/- 40.4 nmol/mg protein/h) compared to brain homogenates. Finally, immunoblots of isolated cerebral microvessels resulted in a pattern of labeling similar to that seen with kidney homogenates. These results indicate that EAP activity in brain is primarily associated with cerebral microvessels, and suggest that EAP may be involved in the metabolism of circulating or locally formed peptides.

Aminopeptidases↗

PubMed1995

Age-related changes in the antioxidative potential of cerebral microvessels.

To determine if aging in rats is associated with increased susceptibility of cerebral microvessels to oxidative damage microvessels from the cerebrum of 4-, 12-, 18- and 26-month-old male Fischer 344 rats were studied. The malondialdehyde (MDA) (micrograms/mg protein) content of cerebral microvessels from 12-month-old rats (0.032 +/- 0.002) was significantly higher than that in 4-month-old rats (0.020 +/- 0.015) P < 0.01. The difference between 26-month-old (0.025 +/- 0.002) and 4-month-old rats did not reach statistical significance. The antioxidative potential was measured in the presence of a peroxy radical generator 2,2'-azobis(2-amidionopropane)hydrochloride (AAPH) with monitoring of the fluorescence of phycoerythrin at 37 degrees C. The free radical quenching activity of cerebral microvessels expressed as % inhibition of phycoerythrin oxidation by AAPH was significantly reduced in 12-month-old (33.6 +/- 4.6%) and 18-month-old rats (26.9 +/- 1.4%) compared with 4-month-old rats (54.3 +/- 4.9%) (P < 0.01). The 26-month-old rats (46.4 +/- 4.6%) were not significantly different from 4-month-old rats. It is concluded that aging is associated with increased lipid peroxidation byproducts in cerebral microvessels along with a transient decrease in their antioxidative capacity.

Aging↗

PubMed1995

The antioxidative potential of cerebral microvessels in experimental diabetes mellitus.

To determine if experimental diabetes is associated with decreased antioxidative potential along with increased peroxidation of lipids in cerebral microvessels, streptozotocin-induced diabetic rats were compared with control rats and to diabetic rats treated with insulin. Isolated cerebral microvessels from diabetic rats had significantly higher concentrations of malondialdehyde (MDA; micrograms/mg protein) (0.0283 +/- 0.0017) compared with control (0.0201 +/- 0.0016) or insulin-treated diabetic rats (0.196 +/- 0.0022) P < 0.01. The antioxidative potential was measured in the presence of a peroxy radical generator 2,2'-azobis(2-amidinopropane) (AAPH) and hydroxyl radical generator CuSO4 with monitoring of the fluorescence of phycoerythrin at 37 degrees C. The free radical quenching activity of cerebral microvessels expressed as % inhibition of phycoerythrin oxidation by AAPH was significantly reduced in diabetic rats (38.7 +/- 4.5%) compared with control (54.3 +/- 4.9%) or insulin-treated diabetic rats (57.6 +/- 2.9%) (P < 0.01). The % inhibition of oxidation by cerebral microvessels in the presence of CuSO4 was only 15.7 +/- 3.1% and did not differ significantly in diabetic rats (13.1 +/- 2.1%). The results indicate that antioxidative potential of cerebral microvessels, especially in the presence of peroxy radical generator, is reduced in diabetes along with increased accumulation of lipid peroxidation byproducts. Increased oxidative stress may be one of the many mechanisms underlying the diabetes-related changes in the blood-brain barrier.

Amidines↗

PubMed1994

Pituitary adenylate cyclase-activating polypeptides (PACAPs) increase cAMP in rat cerebral microvessels.

Effect of PACAP on cAMP level in the rat cerebral microvessels was investigated. The cerebral microvessels were prepared from rat cerebral cortex by albumin flotation and glass beads filtration technique. When the microvessels were incubated with PACAP 27, PACAP 38 and VIP, cAMP in the microvessels was increased rapidly reaching a plateau value within 60 s. PACAP 27, PACAP 38 and VIP increased cAMP level in a dose-dependent manner with EC50 values of 4.7, 7.0 and 34 nM, respectively. These results suggest that PACAPs play a role in the regulation of the cerebral microvessel function.

Animals↗

PubMed1995

Vasodilatory actions of calcitonin gene-related peptide and nitric oxide in parenchymal microvessels of the rat hippocampus.

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are potent dilators in a variety of vascular beds. Recent evidence suggests that NO may serve as an intermediary messenger for CGRP and/or CGRP may serve as an intermediary messenger for NO in the expression of vasodilation. The present study was designed to provide an initial characterization of the responses to NO and CGRP in parenchymal microvessels and to determine whether NO and/or CGRP act as intermediaries for one another. Microvessels in the parenchyma of in vitro hippocampal slices from rat brain were examined using computer-assisted videomicroscopy. The resting diameter of the microvessels ranged from 9 to 26 microm. Treatment with the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (L-NNA; 100 microM) constricted vessels to 64.2% +/- 3.0% of resting luminal diameter. Sodium nitroprusside (SNP; 1 microM), a donor of NO, reversed the L-NNA-induced vasoconstriction by 77.0% +/- 15.0%. CGRP alone (10 nM) elicited a small but significant vasodilatory effect on resting vascular tone (2.3% +/- 0.6%). In the presence of L-NNA, CGRP elicited a significant dose-dependent vasodilatory response, and 10 nM CGRP elicited a sizeable response, reversing the L-NNA-induced constriction by 84.3% +/- 15.5%. This CGRP-induced dilation was inhibited by pretreatment with the CGRP receptor antagonist, CGRP fragment (8-37) (1 microM). In contrast, pretreatment with 1 microM CGRP fragment (8-37) did not attenuate the SNP-induced dilation in the presence of L-NNA. Taken together, these findings demonstrate that CGRP and NO are potent dilators of parenchymal microvessels, and that NO provides a substantial relaxant effect on resting tone. In addition, the results indicate that CGRP is not a necessary intermediary in NO-induced dilation, and that NO is not a necessary intermediary in CGRP-induced dilation in parenchymal microvessels.

Animals↗

PubMed1996

Mast cells accompany microvessels in human coronary atheromas: implications for intimal neovascularization and hemorrhage.

Mast cells have been assigned a role in neovascularization. Therefore, we examined the deep regions of human coronary atheromas, the areas known to be prone to neovascularization, for the presence of mast cells. Specimens of atherosclerotic human coronary intima from 37 autopsy cases with ages of 24-84 years were stained with elastica-van Gieson to detect atheroma formation and with monoclonal antibody against von Willebrand factor to detect neovascularization. Mast cells were detected by staining the atheromas with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase. Of the 24 coronary atheromas found, 13 contained mast cells in the deep regions. All these 13 deep regions also displayed neovascularization, and the number of microvessels and the number of mast cells around the microvessels correlated strongly with the size of the atheroma. On the other hand, of the 11 deep regions lacking mast cells, only one displayed neovascularization. In the neovascularized areas of the coronary atheromas, the mast cells were in close proximity to the microvessels. All the mast cells contained tryptase, and some of them chymase, both known for their angiogenic and matrix-degrading potential. In light microscopic studies, degranulated mast cells were observed indicating activation of these cells, with release of tryptase and chymase. The selective localization of activated mast cells containing angiogenic factors around newly formed microvessels in human coronary atheromas suggests that mast cells play a role in the neovascularization of these lesions. Moreover, mast cells may also, by virtue of their neutral proteases, injure the microvessels, and thereby produce intraplaque hemorrhages and, ultimately, unstable lesions.

Adult↗

PubMed1996

Microvessel basement membrane reduplication is not associated with repeated nerve fiber degeneration and regeneration.

To determine whether repeated nerve fiber degeneration and regeneration can induce reduplication of endoneurial microvessel basement membranes (BMs), typical of such conditions as diabetic polyneuropathy, electronmicrographs of endoneurial microvessels of rat peroneal and tibial nerves were studied in repeatedly crushed (10 x) sciatic nerves and compared to microvessels of sham-operated uncrushed nerves. On average, crushed nerves had 2.6, SE +/- 0.1 BMs, whereas control nerves had 2.7, SE +/- 0.1 (P > 0.05). Microvessel cellular components were significantly increased in both number and size in the crushed nerves. These nerves also demonstrated a trend to increased vessel numbers and density. These results are not in keeping with the hypothesis that BM reduplication of endoneurial microvessels is simply due to repeated fiber degeneration and regeneration.

Animals↗

PubMed1994

Adenosine triphosphatases of rat cerebral microvessels. Effect of age and diabetes mellitus.

To determine the effect of age and diabetes mellitus on the activity of various adenosine triphosphatases (ATPases) of cerebral microvessels, streptozotocin-induced diabetic rats, and aged rats (26 months old) were compared to young control rats (4 months old). The results indicate that diabetic rats have reduced ATPase inhibition by N-ethylmaleimide (NEM), a vacuolar proton (H+)-ATPase inhibitor (98.7 +/- 0.81% vs 78.9 +/- 4.3% of buffer, p < 0.05). Aged rat cerebral microvessels also had reduced NEM sensitive ATPase activity. Sodium-potassium (Na(+)-K(+)-) or magnesium ATPase activity of cerebral microvessels was not altered with diabetes or aging. The changes in cerebral microvessels were distinct from those found in synaptosomal membranes indicating cell specificity of the findings. The results indicate that the age-related and diabetes-related changes in the activity of ATPases in cerebral microvessels are similar but not identical. These changes may contribute to the altered blood-brain barrier functions found in diabetic and aged rats.

Adenosine Triphosphatases↗

PubMed1988

Actions of insulin and insulinlike growth factors I and II in cultured microvessel endothelial cells from bovine adipose tissue.

Endothelial cells were cultured from bovine adipose microvessels, pulmonary arteries, and aortas. The effects of insulin, IGF-I, and IGF-II (MSA) on glucose uptake, neutral amino acid (AIB) uptake, and thymidine incorporation into DNA by the endothelial cells were determined. Each hormone markedly stimulated all three processes in the microvessel endothelial cells but had no effect on the larger-vessel endothelial cells. In the microvessel cells the monoclonal antiinsulin receptor antibody, Ab 47-9, was observed to specifically inhibit insulin binding in the bovine microvessel cells without having intrinsic activity on the three biologic processes that were stimulated by insulin and the IGFs. When insulin binding was first inhibited by Ab 47-9, dose-response curves for insulin were markedly shifted to the right for glucose uptake, AIB uptake, and thymidine incorporation into DNA. Similar antibody treatment had no effect on dose-response curves of IGF stimulation of any of the three processes. These data further extend the biologic actions of insulin and the IGFs in cultured microvessel endothelial cells. They also suggest that certain functions mutually stimulated by both insulin and the IGFs, ie, glucose uptake, AIB uptake, and thymidine incorporation into DNA, are substantially mediated through homologous receptors.

Adipose Tissue↗

PubMed1988

The influence of circulatory overload on extraalveolar microvessel endothelium of dog lung in vivo.

In an earlier study from this laboratory, morphometric evaluations of the alveolar capillary endothelium of the lungs of intact dogs were recorded after periods of sustained increases of pulmonary microvascular pressures (D. O. DeFouw, W. O. Cua, and F. P. Chinard, 1983, Microvasc. Res. 25, 56-67). In the present study ultrastructural characteristics of the extraalveolar microvessel endothelium of these dog lungs were evaluated. Small (25- to 50-microns luminal diameter) nonmuscular vessels, which adjoin the alveolar capillaries, and larger (51-200 microns) partially muscular and muscular microvessels were assessed. After increased microvascular filtration, to be expected from the increased hydrostatic pressures, fluid accumulation was found only in the connective tissue sleeves of the larger microvessels. The endothelium of these partially muscular and muscular vessels was markedly affected by fluid distension of the periendothelial interstitium. The endothelial response included the appearance of basal (abluminal) surface invaginations, de novo plasmalemmal vesicle formation, and increased numbers of cytoplasmic vacuoles. The small nonmuscular microvessels lacked both the fluid cuffs and the alterations of endothelial ultrastructure. This latter observation is consistent with the previous report from this laboratory that indicated an absence of both alveolar septal edema and increased capillary endothelial vesicle densities in these lungs (DeFouw et al., 1983). Thus, it seems likely that the conformational changes of the endothelium of the larger microvessels were related to the formation of the periendothelial fluid cuffs. The mechanisms responsible for this endothelial response have not been determined but can be explained on the basis of the testable hypothesis that they are secondary to an increase of tissue pressure associated with accumulation of tissue fluid. These changes may thus represent a secondary structural adaptation to the increased tissue pressures and may serve as a potential vesicular-vacuolar pathway across the endothelium.

Animals↗

PubMed1988

Metabolic characterization of isolated cerebral microvessels: ATP and ADP concentrations.

Isolated cerebral microvessels (ICMV) have been increasingly used to study microvascular metabolism and function. Despite this, little systematic information exists about their metabolic viability and energy status. To evaluate this, we determined the ATP content and ATP/ADP ratios of ICMV with an ultrasensitive bioluminometric assay which had been adapted for small samples. In calf cerebral microvessels, freshly isolated by a homogenization and sieving procedure, ATP content averaged 1.5 +/- 0.8 nmole/mg protein (mean +/- SE for 45 observations on 18 preparations.) The ATP/ADP ratio for these vessels was 0.96 +/- 0.4. Similar values for ATP were obtained in several preparations of ICMV from dog and rat brain. Values varied considerably in different preparations, probably due to variable degrees of damage incurred during isolation. When microvessel ATP concentrations and ATP/ADP ratios were low, they were dramatically improved by brief incubation (2 hr at 37 degrees) in an enriched tissue culture medium (Dulbecco's modification of Eagle's minimal essential medium, DMEM), or perhaps somewhat less effectively in a buffered saline solution (Earle's-Hepes) containing glucose. Boiling or incubation of microvessels with Triton X-100 lowered ATP values to less than 0.01 nmole/mg protein. The ATP content of our preparations of isolated microvessels was considerably higher than values previously reported by others using similar methods, but still less than that of cultured bovine vascular endothelial cells, even after correction for a 20% difference in intracellular water space.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

PubMed1981

Prostaglandin D synthase in microvessels from the rat cerebral cortex.

Microvessels, a mixture composed predominantly of small arterioles and capillaries (7-80 micro diameter), were isolated from the rat cerebral cortex by selective nylon sieving and glass bead elutriation. The morphology and purity of the microvessel and cerebral cortex filtrate (virtually free of vascular contamination) were monitored by light microscopy and by the activity of several enzymes: gamma -glutamyl transpeptidase, GSH-S-transferase, prostacyclin synthase and PGD synthase. Prostacyclin and PGD synthesizing activities as well as gamma-glutamyl transpeptidase activity were localized to the microvessels of the rat cerebral cortex whereas GSH-S-Transferase was restricted to the non-vascular filtrate fraction. The characteristics of the PGD synthase were similar to those of the purified enzyme previously described for the rat brain. The microvessel (MV) PGD synthase was localized to the cytosol fraction of the microvessels and did not require reduced glutathione for activity. The enzyme was inhibited by pre-incubation with p-hydroxymercuribenzoate (ImM) or N-ethylmaleimide (ImM). The MV RGD synthase saturated at 15-20 microM PGH2, exhibited an apparent Km of 9.6 microM, and a pH optimum of 8.0-8.1. These findings suggest roles for both prostacyclin and PGD synthesis by the rat cerebral vasculature in the autoregulation of cerebral blood flow and/or neural function. These studies also indicate that the major source of PGI2 and PGD2 synthesis by rat brain homogenates is the microvasculature.

Animals↗

PubMed1993

Production of the cytokines interleukin 1 and 6 by murine brain microvessel endothelium and smooth muscle pericytes.

Murine brain microvessel endothelial cells and smooth muscle/pericytes (SM/P) cells were cultured from newborn BALB/c (normal strain) and SJL/j (autoimmune-prone strain) mice. These cells were evaluated for their ability to produce interleukin (IL)-1 and IL-6 cytokines. The expression of mRNA for IL-1 and IL-6 was shown in highly purified BALB/c endothelial cells and SM/P cells using polymerase chain reaction with specific primers for IL-1 alpha, IL-1 beta and IL-6. IL-6 but not IL-1 mRNA was detected in unstimulated SJL/j brain microvessel cells. The presence of IL-1 and IL-6 mRNA in the BALB/c brain microvessel endothelial cells and SM/P was confirmed by in situ hybridization. By D10.G4.1 assay, unstimulated BALB/c endothelial cells were shown to produce active IL-1 to a higher degree than SM/P. By B9 bioassay, a low amount of active IL-6 was detected in the supernatant of endothelial cells and SM/P. The production of IL-1 and IL-6 in the bioassays was upregulated by lipopolysaccharide (LPS) activation of the cells in a time- and dose-dependent way. IL-6 production was also shown to be upregulated by IL-1 beta activation of the cells. Brain microvessel endothelial cells of SJL/j origin released equivalent amounts of IL-6 compared to endothelial cells of BALB/c origin. However, the production of IL-6 was markedly higher in SM/P of SJL/j origin than in those of BALB/c origin. These observations, together with our previous data showing that brain microvessel SM/P cells produce GM-CSF, emphasize the possibility for active participation of brain microvasculature SM/P as well as endothelium in inflammatory reactions of the central nervous system.

Animals↗

PubMed1989

Brain microvessels are innervated by locus ceruleus noradrenergic neurons.

Noradrenergic fibers from the locus ceruleus were identified in close proximity to brain microvessels, and adrenoceptors exist in isolated brain capillaries. Yet, proof of innervation of brain microvessels by locus ceruleus remains elusive. We now demonstrate increased density of beta-adrenoceptors by pindolol binding in microvessels isolated from the norepinephrine-depleted cerebrum two weeks after locus ceruleus lesion or reserpine treatment. This finding of 'denervation supersensitivity' in brain microvessels implies that their adrenoceptors respond to norepinephrine from the locus ceruleus, and strongly suggests that the locus ceruleus innervates brain microvessels. These results may have important implications because blood-brain barrier dysfunction may be a factor in the pathophysiology of Alzheimer dementia and Parkinson disease, which are associated with locus ceruleus degeneration.

Adrenergic Fibers↗

PubMed1989

Effect of several vasoactive agents on guanylate cyclase activity in isolated rat brain microvessels.

We tested the ability of the following putative vasoactive agents to stimulate guanylate cyclase activity in isolated rat cerebral microvessels: angiotensin II, arginine vasopressin, atrial natriuretic peptide, bradykinin, carbachol and thrombin; at concentrations ranging between 10(-3) and 10(-9) M. The ability of cerebral microvessels to increase their cyclic GMP generation was ascertained in the presence of sodium nitroprusside. Of all the agents tested, only atrial natriuretic peptide stimulated cyclic GMP generation in isolated rat cerebral microvessels. Such stimulation was dose-dependent, reaching its maximum at 1 microM concentration. These results are consistent with the finding of atrial natriuretic peptide receptors in brain microvessels, and suggest that this peptide has an important role in modulating the function of brain capillaries, which constitute the blood-brain barrier. If receptors for the other vasoactive agents exist in brain microvessels, their action does not seem to be mediated by cyclic GMP as a second messenger.

Angiotensin II↗

PubMed1992

The effect of experimentally induced diabetes mellitus on the lipid order and composition of rat cerebral microvessels.

To determine whether diabetes mellitus alters the lipid order and composition of cerebral microvessels, streptozotocin-induced diabetic rats were studied after 5 weeks of chronic hyperglycemia. Diabetes did not affect membrane order or the thermotropic transition temperature of cerebral microvessels as determined from the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH). The cholesterol, phospholipid and fatty acid composition of isolated cerebral microvessels was also not significantly affected in diabetic rats. On the other hand, the cerebral microvessels of diabetic rats had significantly increased concentration of lipid peroxidation byproducts, namely conjugated dienes (the calculated O.D./mg phospholipids was 6.98 +/- 0.52 in controls and 11.82 +/- 0.40 in diabetic rats (P < 0.01). The accumulation of conjugated dienes in cerebral microvessels of diabetic rats in the absence of an alteration in the availability of substrates for peroxidation is consistent with the hypothesis that diabetes mellitus is a disease state which is associated with increased free radical activity. Increased oxidative damage may contribute to the changes in the blood-brain barrier observed in animal models of diabetes.

Animals↗