Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Permeability”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 1,189 records · Page 66Linked to original sources
PubMed1996

Increased oligonucleotide permeability in keratinocytes of artificial skin correlates with differentiation and altered membrane function.

We tested the permeability of fluorescent oligonucleotides in cultured human epidermal keratinocyte monolayers and keratinocytes grown in a 3-dimensional skin model. Oligonucleotide permeability in living cells was determined by confocal microscopy after either simple addition to the culture medium or topical application via oligonucleotide-saturated filters placed atop the artificial skin. In cultured monolayers, few keratinocytes (9%) were found to acquire intracellular oligonucleotides that were primarily localized to the nucleus. In contrast, keratinocytes grown in an artificial, 3-dimensional skin matrix acquired extensive oligonucleotide permeability as differentiation progressed. About 95% of the granular cells showed nuclear accumulation of oligonucleotides. About 70% of the oligonucleotide-permeable granular cells were viable as verified by a mitochondria-specific, potential-sensitive dye, tetramethyl rhodamine ethyl ester. A marker used to study apoptotic cells with altered membrane potential, merocyanine 540, was found elevated in the cytoplasm of granular cells. In contrast, cultured keratinocyte monolayers or basal keratinocytes of skin showed a membrane staining pattern typical of undifferentiated cells. Few cells (<3%) of the basal layer had nuclear oligonucleotides, but none of the labeled cells were viable. These results suggest that the development of oligonucleotide and merocyanine 540 permeability in differentiated granular cells parallels the changes in membrane permeability found in other apoptotic systems.

Base Sequence↗
PubMed1996

Increased oligonucleotide permeability in keratinocytes of artificial skin correlates with differentiation and altered membrane function.

We tested the permeability of fluorescent oligonucleotides in cultured human epidermal keratinocyte monolayers and keratinocytes grown in a 3-dimensional skin model. Oligonucleotide permeability in living cells was determined by confocal microscopy after either simple addition to the culture medium or topical application via oligonucleotide-saturated filters placed atop the artificial skin. In cultured monolayers, few keratinocytes (9%) were found to acquire intracellular oligonucleotides that were primarily localized to the nucleus. In contrast, keratinocytes grown in an artificial, 3-dimensional skin matrix acquired extensive oligonucleotide permeability as differentiation progressed. About 95% of the granular cells showed nuclear accumulation of oligonucleotides. About 70% of the oligonucleotide-permeable granular cells were viable as verified by a mitochondria-specific, potential-sensitive dye, tetramethyl rhodamine ethyl ester. A marker used to study apoptotic cells with altered membrane potential, merocyanine 540, was found elevated in the cytoplasm of granular cells. In contrast, cultured keratinocyte monolayers or basal keratinocytes of skin showed a membrane staining pattern typical of undifferentiated cells. Few cells (<3%) of the basal layer had nuclear oligonucleotides, but none of the labeled cells were viable. These results suggest that the development of oligonucleotide and merocyanine 540 permeability in differentiated granular cells parallels the changes in membrane permeability found in other apoptotic systems.

Base Sequence↗
PubMed1987

Effect of dimethylsulfoxide concentration on the permeability of neonatal rat stratum corneum to alkanols.

The effect of dimethylsulfoxide (DMSO) concentration on the permeability of neonatal rat stratum corneum to 14C labeled propan-1-ol and hexan-1-ol was studied in vitro. The permeability coefficients were determined from a range of DMSO-water systems. After soaking in water overnight, the same stratum corneum was used with water as both delivery and recipient phases for the alkanols. Concentrations below 70% DMSO reduced the penetration rate as a result of the solvent effect of DMSO and the formation of a DMSO-alkanol complex. Above 70% DMSO permeability increased, with a permeability coefficient greater than that from water being achieved at concentrations in excess of 80% DMSO. The second run, with water as delivery phase, showed that the effect was reversible below 70% DMSO, but that at higher concentrations DMSO had produced an irreversible change in the permeability of stratum corneum. We hypothesize a hydrogen bond-mediated mechanism for the increased permeability.

1-Propanol↗
PubMed1980

Permeability of thermally damaged skin: I. Immediate influences of 60 degrees C scalding on hairless mouse skin.

Freshly sacrificed hairless mice were burned dorsally by direct contact with 60 degrees C water for periods ranging from 15 seconds to 8 min. Wounds ranging in degree from superficial epidermis damage to injury penetrating well into subcutaneous musculature were inflicted. Burned skin sections and reference abdominal skin sections were excised, placed in diffusion cells and investigated with regards to their permeabilities to water, methanol, ethanol, n-butanol and n-octanol. The data were couched in terms of ratios of permeability coefficients of burned skin to normal skin (scalding coefficients) for the same animal. Scalding increased permeability of skin to all compounds studied but the effects leveled out by 60 seconds. Protracted scalding was without great effect despite progressively increased depth of damage to the tissue as noted in histological sections. The degree of lost barrier competency attributable to 60 degrees C scalding was not marked for any compound but was definitely different for different alkanols. An approximately 3-fold permeability increase was noted with n-butanol, the most affected compound. The data demonstrate that near instantaneous alterations in permeability of skin accompany scalding, that decreased barrier competency does not correlate with the severity of a burn as measured in depth of the burn, and that thermal alteration of permeabilities is dependent on the physicochemical characteristics of the permeants.

Abdomen↗
PubMed2004

Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario.

BACKGROUND: Post-infectious irritable bowel syndrome is a common clinical phenomenon of uncertain aetiology. AIM: To test the association between intestinal permeability and irritable bowel syndrome symptoms 2 years after a large waterborne outbreak of bacterial gastroenteritis. METHODS: Consecutive adults with Rome I irritable bowel syndrome and controls without irritable bowel syndrome attending a community clinic were enrolled. Intestinal permeability was measured as the ratio of fractional urinary excretions of lactulose and mannitol, and compared among cases vs. controls and predictors of abnormal intestinal permeability were assessed. RESULTS: A total of 218 subjects (132 irritable bowel syndrome cases and 86 non-irritable bowel syndrome controls) completed the study protocol. About 27 (12%) had been diagnosed with the irritable bowel syndrome before the outbreak and 115 (53%) had been ill during the outbreak. Lactulose-mannitol ratios were increased among cases vs. controls (Mann-Whitney mean rank 118.8 vs. 95.3, P = 0.007), and cases were more likely to have a ratio >0.020 (P = 0.007). Among cases, those with increased intestinal permeability were more likely to report increased stool frequency. Both irritable bowel syndrome symptoms and male gender, but not diarrhoeal illness during the outbreak, were significant predictors of abnormal permeability. CONCLUSIONS: Irritable bowel syndrome symptoms are associated with a subtle increase in intestinal permeability irrespective of prior gastroenteritis. This may improve understanding of the aetiology of both sporadic and post-infectious irritable bowel syndrome.

Acute Disease↗
PubMed2006

Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's disease.

BACKGROUND: Abnormal barrier function may be genetically determined in Crohn's disease. AIM: To examine the role of abnormal intestinal permeability in genetic predisposition in multiplex vs. sporadic Crohn's disease families. METHODS: Intestinal permeability was measured in patients, relatives and partners by means of lactulose/mannitol test. Healthy subjects from the hospital staff served as controls. CARD15 mutations were investigated in sporadic and familial Crohn's disease patients and in a group of blood donors. RESULTS: The median lactulose/mannitol ratio was increased significantly in Crohn's disease patients vs. their relatives [0.03 (0.01-0.24) vs. 0.01 (0.003-0.19), P=0.005]. The percentage of abnormal tests was significantly higher in familial vs. sporadic first-degree relatives of Crohn's disease patients (29% vs. 11%, P=0.0281). Abnormal permeability occurred significantly more frequent in patients with familial Crohn's disease carrying the frameshift mutation. The frameshift mutation 3020 insC was associated with increased permeability in 75% in the multiplex and in 61% of the sporadic CD patients. One partner had abnormal lactulose/mannitol ratio. Conclusion Intestinal permeability is raised in Crohn's disease patients and relatives, with higher rates in familial vs. sporadic healthy relatives. CARD15 mutations are associated with abnormal permeability in ileal Crohn's disease.

Adult↗
PubMed1985

Intestinal permeability in patients with atopic eczema.

Intestinal permeability was investigated in adult patients with atopic eczema by in vivo and in vitro techniques. Patients with symptoms of 'immediate' food allergy were specifically excluded. A 51Cr-labelled ethylenediaminetetraacetate absorption test was carried out in eighteen patients. Their mean (+/- s.d.) 24-hour urine excretion following oral administration of the test substance (2.1 +/- 0.9%) did not differ significantly from that of thirty-four normal controls (1.9 +/- 0.5%). Small bowel permeability was estimated directly in jejunal mucosal samples in ten patients with three permeability probes of differing molecular weight. Mucosal permeability did not differ significantly from that of fifteen control patients for any of the test substances. Two patients had abnormal results by both tests and in one this was due to coeliac disease. These results suggest that altered intestinal permeability is not important in the pathogenesis of eczema. Patients demonstrating increased intestinal permeability should undergo jejunal biopsy to exclude significant small bowel disease.

Adolescent↗
PubMed2004

Permeability of synthetic and feather pillows to live house dust mites and house dust.

BACKGROUND: Previous studies have demonstrated significantly higher house dust mite (HDM) allergen levels from synthetic pillows, compared to feather pillows. Reasons for these differences could be lower permeability of feather pillow coverings to allergen in dust, greater HDM penetration of synthetic pillow covering, or both. OBJECTIVES: To determine the permeability of synthetic and feather pillow coverings to live HDMs and house dust. METHODS: Twenty live adult HDMs were seeded on top of two types of synthetic pillow covering (one standard polyester and one newer polyester/cotton type) and one type of feather pillow coverings with adequate food supply below in sealed culture dishes, kept at 23 degrees C and 70% relative humidity. After 24 and 48 h live HDM numbers remaining on top of the coverings were enumerated microscopically. Three aliquots of fine house dust (each in triplicate) were placed on top of the synthetic and feather pillow coverings, shaken gently for 30 min and penetrated dust was collected and weighed. RESULTS: After 24 h, all 20 HDMs had penetrated the standard synthetic pillow coverings, and no HDMs had penetrated either the feather pillow or the new synthetic pillow coverings after 24 or 48 h. Dust permeability (% of applied dust) for the standard synthetic, new type synthetic and feather pillow coverings were 0.88%, 0.07%, and 0.07%, respectively. This compared to 0.02% for a commercial occlusive pillow cover. CONCLUSIONS: These findings of total permeability of standard synthetic pillow coverings to live HDMs, and their greater permeability to house dust could explain their reported higher HDM allergen levels, compared to feather pillow coverings. Newer types of synthetic pillow coverings are similar to feather pillow coverings in their permeability to live HDMs and house dust.

Allergens↗
PubMed2006

Alveolar-capillary membrane permeability for early prediction of response of inhaled steroid on patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Glucocorticosteroid reversibility-testing is undertaken over a period of 3 months to identify whether patients with chronic obstructive pulmonary disease (COPD) would benefit from long-term inhaled corticosteroids. This study assessed whether alveolar-capillary membrane (a/c) permeability testing can be used as an early alternative test method for the same purpose. METHODS: Fourteen patients with severe and symptomatic moderate COPD (group S) were prescribed inhaled steroid 800 microg/day for 3 months. Before inhalation and 4 weeks after inhalation therapy, forced expiratory volume in 1 s (FEV(1)) and a/c permeability using (99m)Tc-DTPA were performed. FEV(1) was recorded again at the end of the third month. Another 10 patients with COPD of comparable severity (group B) prescribed with inhaled bronchodilators were examined and studied as controls. RESULTS: In group S, the permeability decreased in eight patients (group D) and increased in six patients (group I). No significant change was noted in FEV(1) at the end of the first month. However, seven patients in group D showed significant improvement in FEV(1) at the end of the third month, whereas in patients in group I no significant changes were observed. In group B, no significant change in a/c permeability was observed, although the FEV(1) increased by 12-17%. CONCLUSION: With steroid inhalation, the a/c permeability at 4 weeks predicts future changes in lung functions. Long-term inhaled corticosteroids are likely to be useful if permeability decreases. This test, which needs further validation, appears to provide much earlier prediction of response than glucocorticoid reversibility testing.

Administration, Inhalation↗
PubMed1991

The adjuvant action of cholera toxin is associated with an increased intestinal permeability for luminal antigens.

This study addresses the question of whether cholera toxin (CT) increases gut permeability for molecules greater than 3000 Da and whether such an effect is associated with an adjuvant function by CT on the gut immune response. We found that CT after oral administration gives rise to strikingly increased gut permeability for Dextran (Mw 3000) concomitantly with a strong enhancing effect on the anti-keyhole limpet hemocyanin (KLH) specific immune response in the lamina propria after oral immunization with KLH plus Dextran and CT. In contrast, the B-subunit of the holotoxin, which lacks the adenylate cyclase/cAMP-activating property of CT, failed to increase gut permeability as well as local anti-KLH immune responses. These results might suggest a causal linkage between the ability of CT to increase gut permeability and its adjuvant property on gut mucosal immune responses. In addition this finding supports the notion that the adenylate cyclase/cAMP system plays a regulatory role in gut permeability and is important in enhancing mucosal immune responses. Based on previous studies and the present data we propose that the mechanism for CT's adjuvant function on mucosal immune responses is by affecting antigen-presenting cells, T and B cells in the gut to give a net enhancing effect on the stimulation of local immunity, and that the CT-induced increase in gut permeability might be part of the adjuvant mechanism by facilitating luminal antigens to access the gut mucosal immune system.

Adenylyl Cyclases↗
PubMed1998

Conformational and topological requirements of cell-permeable peptide function.

Cell-permeable peptide import recently was developed to deliver synthetic peptides into living cells for studying intracellular protein functions. This import process is mediated by an N-terminal carrier sequence which is the hydrophobic region of a signal peptide. In this study, the conformational consequence of the interaction of cell-permeable peptides with different mimetic membrane environments was investigated by circular dichroism analysis. We showed that cell-permeable peptides adopted alpha-helical structures in sodium dodecyl sulfate (SDS) micelles or aqueous trifluoroethanol (TFE). The potency of these peptides in forming helical structures is higher in an amphiphilic environment (SDS) than in a hydrophobic environment (TFE), suggesting that some hydrophilic molecules associated with the cell membrane may be involved in peptide import. We also studied topological requirements of cell-permeable peptide function. We demonstrated that peptides containing the carrier sequence in their C-termini can also be imported into cells efficiently. This important discovery can avoid repetitious synthesis of the membrane-translocating sequence for peptides with different functional cargoes and is potentially useful for developing a cell-permeable peptide library. Finally, we showed that, when a retro version of the carrier sequence was used, the peptide lost its translocating ability despite retaining a high content of alpha-helical structure in mimetic membrane environments. This suggests that the propensity of peptides to adopt a helical conformation is required but not sufficient for cellular import and that other structural factors such as the side-chain topology of the carrier sequence are also important. Our studies together contribute to the more rational design of useful cell-permeable peptides.

3T3 Cells↗
PubMed1993

An analysis of Bacillus thuringiensis delta-endotoxin action on insect-midgut-membrane permeability using a light-scattering assay.

Changes in the membrane permeability of Manduca sexta midgut brush-border-membrane vesicles (BBMV) after addition of Bacillus thuringiensis delta-endotoxins were studied using osmotic swelling experiments, volume changes being monitored as the change in 90 degrees light scattering. Typically, control BBMV exhibited limited permeability for sucrose and salts (KCl), while being permeable for urea and glucose. The action of delta-endotoxin was examined using proteolytically activated Cry-IA(c) and CryIB toxins. CryIA(c) produced a marked change in the solute permeability of M. sexta BBMV, significant effects being observed at 3.75 pmol/mg BBMV. The permeability change was relatively non-selective with cations, anions and neutral solutes all traversing the membrane to an increased extent in the presence of CryIA(c). In contrast, the CryIB toxin had no effect on BBMV permeability.

Animals↗
PubMed1975

Changes in vascular permeability in stroke-prone spontaneously hypertensive rats studied with peroxidase as a tracer.

Cerebrovascular permeability in stroke-prone spontaneously hypertensive rats (SHR) at various ages was histologically studied using horseradish peroxidase as a tracer and such was related to the cerebrovascular lesions in the animals. An increase in permeability was demonstrated in the brain of SHR, particularly in those animals with an extremely high blood pressure. Increased cerebrovascular permeability occurred in some animals without any organic vascular change or severe parenchymal changes, although edema was present. Histologically, the SHR brain with an increase in permeability showed mild focal edema, rarefaction of tissue and necrosis with cyst formation. Thus a transitional progress was evident. Localization of the increase in permeability corresponded well with the predilection sites of cerebrovascular lesions in SHR. Constrictions and dilatations of intracerebral arterioles and small arteries were also demonstrated by the peroxidase method, and the dilated arterial walls did reveal a darker staining. From these results it is strongly suggested that certain cerebrovascular lesions, especially necrosis with cyst formation in SHR are sequelae of the increased cerebrovascular permeability caused by a chronic hypertensive state.

Animals↗
PubMed2005

Connexin26 is responsible for anionic molecule permeability in the cochlea for intercellular signalling and metabolic communications.

Abstract A gap junction is composed of two hemichannels and possesses a relatively large pore size ( approximately 10-15 A), allowing passage of ions and molecules up to 1 kDa. Here, we report that connexin hemichannels and gap junctions in the guinea pig cochlea had significant charge selectivity among permeating molecules. In coincubation with anionic and cationic fluorescent dyes, hemichannel permeability in isolated cochlear supporting cells showed significant charge selectivity; 31% of cells had only cationic dye influx and 6% of cells had only anionic dye influx. Charge-selective influx contrary to dye size was also found, indicating charge as a dominant determinant in permeability. The cell-cell gap junctional permeability was consistent with hemichannel permeability and also showed strong charge selectivity; the permeation of anionic dyes was slower than that of cationic probes in the cochlear sensory epithelium. With a combination of immunofluorescent staining for connexin26 (Cx26) and Cx30, which are the predominant connexin isoforms in the cochlea, Cx26 was demonstrated to correlate with anionic permeability. The data indicated that cochlear gap junctions have strong charge selectivity in molecular permeability and metabolic communication. Cx26 mutation may induce specific, irreparable impairment in intercellular signalling and energy and nutrient supplies in the cochlea, causing cell degeneration and hearing loss, given that many important cell-signalling and nutrient and energy molecules (e.g. IP3, ATP, cAMP and cGMP) are anions.

Adenosine Triphosphate↗
PubMed2005

Long-term changes in blood-brain barrier permeability and white matter following prolonged systemic inflammation in early development in the rat.

Epidemiological evidence in human fetuses links inflammation during development with white matter damage. Breakdown of the blood-brain barrier has been proposed as a possible mechanism. This was investigated in the present study by inducing a prolonged inflammatory response in newborn rats, with intraperitoneal injections of lipopolysaccharide (LPS; 0.2 mg/kg) given at postnatal (P) day 0, P2, P4, P6 and P8. An acute phase response was present over the whole period of injections. Changes in blood-brain barrier permeability were determined for small (sucrose and inulin) and large (protein) molecules. During and immediately after the inflammatory response, plasma proteins were detected in the brain only within white matter tracts, indicating an increased permeability of the blood-brain barrier to protein during this period. The alteration in permeability to protein was transient. In contrast, the permeability of the blood-brain barrier to 14C-sucrose and 14C-inulin was significantly higher in adult animals that had received serial LPS injections during development. Adult animals receiving a single 1 mg/kg LPS injection at P0 showed no alteration in blood-brain barrier permeability to either small or larger molecules. A significant decrease in the volume of CNPase immunoreactive presumptive white matter tracts occurred in the external capsule and corpus callosum at P9. These results demonstrate that a prolonged systemic inflammatory response in the early postnatal period in rats causes size selective increases in blood-brain barrier permeability at different stages of brain development and results in changes in white matter volume.

Animals↗
PubMed1999

Permeability and single channel conductance of human homomeric rho1 GABAC receptors.

1. Homomeric human rho1 GABAC receptors were expressed in Xenopus oocytes and in human embryonic kidney cells (HEK293) in order to examine their conductance and permeability. 2. Reversal potentials of currents elicited by gamma-aminobutyric acid (GABA) were measured in extracellular solutions of various ionic composition to determine relative permeability of homomeric rho1 receptors. The rank order of anionic permeability was: SCN- > I- > NO3- > Br- > Cl- > formate (For-) > HCO3- > acetate (Ac-) approximately proprionate (Prop-) approximately isethionate (Ise-) approximately F- approximately PO4-. 3. In the oocyte expression system, relative permeabilities to SCN-, I-, NO3-, Br- and HCO3- were higher for rho1 GABAC receptors than alpha1beta2gamma2L GABAA receptors. 4. Expression of rho1 GABAC receptors in Xenopus oocytes and in HEK293 cells gave similar relative permeabilities for selected anions, suggesting that the expression system does not significantly alter permeation properties. 5. The pore diameter of the homomeric rho1 GABAC receptor expressed in oocytes was estimated to be 0.61 nm, which is somewhat larger than the 0.56 nm pore diameter estimated for alpha1beta2gamma2L GABAA receptors. 6. Homomeric rho1 GABA receptors expressed in oocytes had a single channel chord conductance of 0.65 +/- 0.04 pS (mean +/- s.e.m.) when the internal chloride concentration ([Cl-]i) was 20 mM. With a [Cl-]i of 100 mM, the single channel chord conductance was 1.59 +/- 0.24 pS. 7. The mean open time directly measured from 43 GABA-induced channel openings in six patches was 3. 2 +/- 0.8 s. The mean open time in the presence of 100 microM picrotoxin was 0.07 +/- 0.01 s (77 openings from 3 patches). 8. The differences observed in ionic permeabilities, pore size, single channel conductance and mean open time suggest that the rho1 homomeric receptor may not be the native retinal GABAC receptor reported previously.

Animals↗
PubMed2000

Acute effects of bradykinin on cerebral microvascular permeability in the anaesthetized rat.

1. The permeability response to acutely applied bradykinin and [des-Arg9]-bradykinin on single cerebral venular capillaries has been investigated using the low molecular mass fluorescent dyes Lucifer Yellow and Sulforhodamine B with the single vessel occlusion technique. 2. When bradykinin was applied repeatedly for up to 2 h, the permeability increase was small and reversible for concentrations that ranged from 5 nM to 50 microM. 3. The logEC50 of the permeability response to bradykinin was -5.3 +/- 0.15 (logM; mean +/- s.e.m.). This was reduced to -6.37 +/- 0.24 with the angiotensin-converting enzyme inhibitor captopril, to -6.33 +/- 0.19 with the neutral endopeptidase inhibitor phosphoramidon and to -7.3 +/- 0.20 with captopril and phosphoramidon combined. 4. The permeability response to bradykinin was blocked by the bradykinin B2 receptor antagonist HOE 140, by inhibition of the Ca2+-independent phospholipase A2, by the scavenging of free radicals, or by inhibition of both cyclo-oxygenase and lipoxygenase in combination. Block of Ca2+ entry channels with SKF 96365 had no effect on the response. 5. Application of [des-Arg9]-bradykinin also increased permeability over the concentration range 5 nM to 50 microM, with a logEC50 of -5.6 +/- 0. 37. This response was not affected by free radical scavenging, but was completely blocked by the histamine H2 receptor blocker cimetidine. 6. These results imply that the acute permeability response to bradykinin is mediated via the release of arachidonic acid, which is acted on by cyclo-oxygenase and lipoxygenase resulting in the formation of free radicals, and that the response to [des-Arg9]-bradykinin is mediated via histamine.

Anesthesia↗
PubMed2001

Permeability and route of entry for lipid-insoluble molecules across brain barriers in developing Monodelphis domestica.

1. We have studied the permeability of blood-brain barriers to small molecules such as [(14)C]sucrose, [(3)H]inulin, [(14)C]L-glucose and [(3)H]glycerol from early stages of development (postnatal day 6, P6) in South American opossums (Monodelphis domestica), using a litter-based method for estimating steady-state cerebrospinal fluid (CSF)/plasma and brain/plasma ratios of markers that were injected I.P. 2. Steady-state ratios for L-glucose, sucrose and inulin all showed progressive decreases during development. The rate of uptake of L-glucose into the brain and CSF, in short time course experiments (7-24 min) when age-related differences in CSF production can be considered negligible also decreased during development. These results indicate that there is a significant decrease in the permeability of brain barriers to small lipid-insoluble molecules during brain development. 3. The steady-state blood/CSF ratio for 3000 Da lysine-fixable biotin-dextran following I.P. injection was shown to be consistent with diffusion from blood to CSF. It was therefore used to visualise the route of penetration for small lipid-insoluble molecules across brain barriers at P0-30. The proportion of biotin-dextran-positive cells in the choroid plexuses declined in parallel with the age-related decline in permeability to the small-molecular-weight markers; the paracellular (tight junction) pathway for biotin-dextran appeared to be blocked, but biotin-dextran was easily detectable in the CSF. A transcellular route from blood to CSF was suggested by the finding that some choroid plexus epithelial cells contained biotin-dextran. 4. Biotin-dextran was also taken up by cerebral endothelial cells in the youngest brains studied (P0), but in contrast to the CSF, could not be detected in the brain extracellular space (i.e. a significant blood-brain barrier to small-sized lipid-insoluble compounds was already present). However, in immature brains (P0-13) biotin-dextran was taken up by some cells in the brain. These cells generally had contact with the CSF, suggesting that it is likely to have been the source of their biotin-dextran. Since the quantitative permeability data suggest that biotin-dextran behaves similarly to the radiolabelled markers used in this study, it is suggested that these markers in the more immature brains were also present intracellularly. Thus, brain/plasma ratios may be a misleading indicator of blood-brain barrier permeability in very immature animals. 5. The immunocytochemical staining for biotin-dextran in the CSF, in contrast to the lack of staining in the brain extracellular space, together with the quantitative permeability data showing that the radiolabelled markers penetrated more rapidly and to a much higher steady-state level in CSF than in the brain, suggests that lipid-insoluble molecules such as sucrose and inulin reach the immature brain predominantly via the CSF rather than directly across the very few blood vessels that are present at that time.

Algorithms↗