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At least 937 records · Page 52Linked to original sources
PubMed1998

First use of cultured human urothelial cells for biocompatibility assessment: application to urinary catheters.

For several years, studies performed to estimate in vitro biocompatibility of urinary catheters have been carried out using permanent cell lines. But for a rational design of the testing procedure, the cell culture model should relate to the material application. This work presents the results of a probe study designed to obtain an in vitro model of normal human urothelial cells (HUC) and to test the relevance of this system in cytocompatibility experiments of urinary catheters currently used.A comparison is made with continuous cell lines, the use of which is recommended by normalization bodies. We exposed monolayers of HUC (well characterized for their proliferation, qualitative evaluation, and quantitative measurement of cytokeratins) and two continuous human cell lines to liquid extracts (either pure or diluted in the culture medium) of nine available catheters, including positive (latex) and negative controls, for a 24 h incubation. Then colorimetric assays (Neutral Red and MTT) were performed. The extracts of two polyurethanes provoked a significant toxic effect on HUC only, suggesting differences in sensitivity between the models used. This effect could be due to the presence of a great amount of barium (used as a radioopacifier) in extracts, as highlighted by results of absorption emission spectroscopy. A culture model of HUC may be of relevance for the screening of materials intended for urological practice.

Biocompatible Materials↗
PubMed1998

Effects of titanium-dental restorative alloy galvanic couples on cultured cells.

The potential exists for titanium and amalgams to become galvanically coupled in the oral cavity. While low galvanic corrosion rates have been measured in vivo for titanium-amalgam or mercury-free alloy couples, concerns exist over released corrosion products and adverse tissue responses. It was hypothesized in this study that coupling titanium to amalgams or gallium alloys increased the release of metallic corrosion products and decreased cellular activity and function. The effects of titanium coupled and uncoupled to a conventional amalgam, palladium-enriched spherical high copper amalgam, a dispersed type high copper amalgam, and a mercury-free gallium alloy were evaluated in 24-h cell culture tests. Viability, proliferation, and collagen synthesis were evaluated by the uptake of neutral red, 3H-thymidine, and immunoassay of procollagen, respectively, and compared to cells not exposed to any test material. The gallium alloy-titanium couple resulted in significant decreases in cellular viability, proliferation, and collagen synthesis as compared to the other coupled and uncoupled samples. Few differences in the cellular responses of the other coupled and uncoupled samples were observed. Atomic absorption analyses indicated increased release of metal ions from the amalgam and gallium alloy samples coupled to titanium as compared to their uncoupled condition, although the differences were not always significant. Galvanic corrosion of amalgam-titanium couples in the long term may become significant, and further research is needed. Coupling the gallium alloy to titanium may result in increased galvanic corrosion and cytotoxic responses.

Cells, Cultured↗
PubMed1997

Mutagenic and cytotoxic activity of an isocoumarin (Paepalantine) isolated from Paepalanthus vellozioides.

A new isocoumarin with antimicrobial activity was isolated from Paepalanthus vellozioides (a native Brazilian plant) and called paepalantine. This study was carried out to assess the mutagenic activity of this new agent in assays with Salmonella typhimurium TA100, TA98, and TA102 and in Chinese hamster ovary (CHO) cell cultures, as well as cytotoxicity to McCoy cells. paepalantine caused a significant dose-dependent increase in the frequency of revertants in the three strains used in the assay, both with and without S9 mix, in concentrations varying from 2 to 128 micrograms/plate. The mutagenicity was confirmed in assays with CHO cells treated in the G1, S, and G2 phases of the cell cycle. There was an increase in the chromosomal aberration frequency, mainly in the G2 phase. Furthermore, the mitotic index of the treated cultures (40,80, and 160 micrograms/ml) was significantly lower, indicating cytotoxicity. The midpoint cytotoxicity values of McCoy cells by the neutral red (NR) and microculture tetrazolium (MTT) techniques resulted in a NR50 and MTT50 of 30 and 38 micrograms/ml, respectively. Alterations to the paepalantine structure are suggested to reduce its mutagenic and cytotoxic activity in investigations for its antineoplastic potential.

Animals↗
PubMed1998

Differences in neurotoxic effects of ochratoxin A, ochracin and ochratoxin-alpha in vitro.

The mycotoxin ochratoxin A (OTA) is a chlorinated dihydroisocoumarin derivative connected through an amide-bond to L-phenylalanine. In a previous study we could show that competition with L-phenylalanine-dependent processes does not play a role in OTA neurotoxicity. To test whether the isocoumarin part is responsible for the neurotoxic effects, we determined in the present study the effects of the hydrolysis product of OTA, ochratoxin-alpha (OTalpha), and of ochracin on embryonic chick brain cell cultures. In addition, we investigated the interaction between OTA and ochracin regarding the neurotoxic effects. We report here that OTalpha did not affect brain cell cultures at concentrations up to 15 microM. With the exception of a small (20%) but significant reduction in cell culture, cellular protein at concentrations above 0.3 microM, in our cell cultures' cell function, as defined by neutral red uptake and MTT-dehydrogenase activity, was only reduced by high OTalpha concentrations (1 mM). Addition of 0.1 microM OTA increased ochracin cytotoxicity as defined by latter parameters. No effects on cell culture NF68kD content could be detected. The results are discussed with regard to the existence of an OTA target interaction binding site.

Animals↗
PubMed2001

In vitro biocompatibility assessment of naturally derived and synthetic biomaterials using normal human urothelial cells.

The reconstruction of urinary tissues often employs various types of biomaterials, and adequate material biocompatibility is essential for the successful reconstruction of urinary tissues. In this study we utilized a primary normal human urothelial cell culture system to evaluate the in vitro biocompatibility of a number of naturally derived biomaterials [i.e., bladder submucosa, small intestinal submucosa, collagen, and alginate] and polymeric biomaterials [i.e., poly(glycolic acid), poly(L-lactic acid), poly(lactic-co-glycolic acid), and silicone] that are either experimentally or clinically used in urinary reconstructive surgery. To determine the cytotoxic and bioactive effects of these biomaterials, the cell viability, metabolic activity, apoptotic properties, and DNA-synthesis activity were measured with four types of assays [Neutral Red, 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl tetrazolium bromide, apoptotic activity, and tritiated thymidine incorporation assays] using extract and direct contact methods. Most of the biomaterials tested did not induce significant cytotoxic effects and exhibited normal metabolic function and cell growth in vitro. This normal primary human urothelial cell culture model is suitable for in vitro biocompatibility assessments and is able to provide information on the cell-biomaterial interactions and the ability of biomaterials to support bioactive cell functions.

Apoptosis↗
PubMed2001

Biocompatible hydrogel supports the growth of respiratory epithelial cells: possibilities in tracheal tissue engineering.

Extensive tracheal defect reconstruction is a major challenge in plastic and reconstructive surgery. The lack of an epithelial lining on the luminal surfaces of tracheal prostheses is among the major causes of their failure. Chitosan-gelatin hydrogels were synthesized for the development of biocompatible, growth-supportive substrata for respiratory epithelial cells. We employed J774 macrophages to test the immunocompatibility of this gel. The hydrogel did not exert a cytotoxic effect on macrophages, as confirmed by tetrazolium reduction and neutral red uptake assay. Flow cytometric analysis of macrophages cultured on the hydrogel showed a comparable expression of activation markers CD11b/CD18, CD45, and CD14 to the control. Semiquantitative RT-PCR results showed an absence of upregulation of interleukin-6 (IL-6) and TNF-alpha in these macrophages with respect to the controls. Primary human respiratory epithelial cells cultured on the hydrogel showed proper attachment, normal morphology, and growth. A small proportion of cells on the hydrogel showed synchronously beating cilia. RT-PCR analysis showed that cells on the hydrogel expressed mucins 2 and 5 and cytokeratin 13, which are markers for secretory goblet and squamous cells, respectively. All these results demonstrate that the hydrogel supports the growth of a mixed population of differentiated epithelial cells. This hydrogel is suitable as a culture substratum for respiratory epithelial cells and could be used as a potential candidate for coating tracheal prostheses.

Biocompatible Materials↗
PubMed2001

Effect of chitosan-polyvinyl pyrrolidone hydrogel on proliferation and cytokine expression of endothelial cells: implications in islet immunoisolation.

Earlier we have shown the suitability of chitosan-polyvinyl pyrrolidone (PVP) hydrogel for islet immunoisolation and its inability to activate macrophages. Biomaterials that support vascularization without activating immune competent endothelial cells are desirous in islet immunoisolation. The aim of the present study was to evaluate effect of chitosan-PVP hydrogel on proliferation and activation of endothelial cells. Hydrogel did not allow the majority of cells to adhere well but maintained their viability. Hydrogel leachouts were nontoxic to the cells, as confirmed by tetrazolium reduction (MTT) and Neutral red uptake assays. Exposure to leachouts also did not alter their functionality as seen from normal expression of von Willebrand factor. 3H-thymidine incorporation revealed that hydrogel leachouts did not induce endothelial cell proliferation. Cells cultured on hydrogel and polystyrene control showed comparable expression of interleukin (IL) 6, IL-10, and transforming growth factor beta, with higher expression of tumor necrosis factor alpha as determined by reverse transcription-polymerase chain reaction. Taken together these results point out that hydrogel is compatible with endothelial cells and maintains their nonactivated status and hence is suitable as immunoisolation matrix.

Biocompatible Materials↗
PubMed2002

Cytochemical assessment of phosphopeptides derived from casein as potential ingredients for functional food.

Phosphopeptides derived from casein hydrolysis are suggested to have beneficial effects beyond their mere nutritive value by enhancing availability of dietary minerals, especially calcium, iron and zinc. Apart from a possible positive action the potential may exist for adverse effects that could impose restrictions to their widespread application in functional foods for human nutrition. In the present work, various case-inophosphopeptide (CPP) preparations were assessed using different human cell culture model systems in order to estimate their cytotoxic potential and their influence on epithelial properties and differentiation of human intestinal cells (Caco-2). The general cytotoxic potential of CPPs was tested using the AlphaTox NR assay. Structural and functional differentiation of intestinal Caco-2 cells was determined by measuring transepithelial electrical resistance and activity of brush border associated alkaline phosphatase over an extended cultivation period. No loss in cell viability with respect to membrane integrity could be detected, as uptake and retention of neutral red dye (AlphaTox assay) into HeLa cells was not affected by the presence of CPPs. Cytochemical assays conducted on epithelial cells (Caco-2) showed no disturbance of normal cell development and differentiation with respect to structural as well as functional differentiation markers. As all CPPs tested did not provoke any adverse effects in terms of cytotoxicity and showed no impairment of cell differentiation and monolayer integrity of human intestinal cells, it may be supposed that CPPs do not provoke a cytotoxic response in vivo in the cells assayed in the present study.

Alkaline Phosphatase↗
PubMed1978

Regulation of Na+ and Cl- transport and mucous gland secretion in airway epithelium.

Ussing's short-circuit technique was applied to canine airway epithelium in vitrol and a net flux of Cl- towards the airway lumen was demonstrated, with a smaller net flux of Na+ in the opposite direction. Furosemide decreased and acetylcholine, terbutaline, and histamine increased net ion transport towards the airway lumen. Associated changes in water content in the airway lumen could affect mucociliary clearance, and therefore inhibition of ion transport may play a role in disease states. To study secretions from submucosal glands in vivo, two techniques were used to identify the duct openings in the exposed canine tracheal epithelium. (a) The exposed mucosal surface was coated with powdered tantalum; accumulated secretions produced elevations under which the duct openings were located. (b) A vital dye (0.1% Neutral red) was placed on the exposed mucosal surface; the dye stained the duct openings. With these techniques, the innervation of the submucosal glands and the autonomic regulation of their secretions were studied. Micropuncture techniques were used to sample the secretions from the glands and ducts.

Acetylcholine↗
PubMed1994

Influence of digits, ectoderm, and retinoic acid on chondrogenesis by mouse interdigital mesoderm in culture.

We have cultured tissues isolated from the interdigital zones (IDZ) of the mouse footplate in the presence of the digits, ectoderm, and all-trans retinoic acid. The objective was to understand how these various factors influence the developmental fate of the interdigital tissues. Neutral red staining showed that these tissues normally differentiate by dying between day 12.5-14.5. However, if they were isolated from the footplate between day 12.5-13.5 (when cell death is not overtly obvious in the IDZ) and maintained in organ culture, these tissues would develop into cartilage and soft connective tissues. In culture, chondrogenesis is initiated very rapidly in the interdigital explants as revealed by in situ hybridization with riboprobes specific for type IIA and IIB procollagen mRNAs. The ability of interdigital tissues to form cartilage is not attributed to factors present in the serum of the culture medium as this phenomenon is also observed in serumless cultures. We have found that if all-trans retinoic acid, at concentrations of 10-50 ng/ml culture medium, were added to the explants it could inhibit chondrogenesis and promote cell death. Moreover, in some of the cultures, a single digit was left attached to the interdigital tissue. This also dramatically reduced the incidence of chondrogenesis. We have tried to determine whether the digits and ectoderm can produce a diffusible factor that can prevent cartilage from developing by culturing day 12.5 interdigital tissues in ectoderm and digit conditioned media. The ectoderm conditioned medium had no effects on interdigital growth or chondrogenesis. In contrast, the size of interdigital explants cultured in the presence of digit conditioned medium was shown to be significantly smaller than the control. These explants also produced a smaller quantity of cartilage as revealed by Alcian blue binding assay. In sum, our results showed that the fate of the interdigital tissues are not fully determined until after day 13.5. These tissues have the potentials to form cartilage and soft connective tissues. We tentatively propose that these interdigital tissues do not normally realize their histogenetic potentials because of the antichondrogenic influence of the digits and retinoic acid.

Animals↗
PubMed1993

Reduced surface area in mitotic rounding of human Chang liver cells.

The rounding up of mitotic human Chang liver cells in monolayer culture was studied quantitatively. It was surprising to find significant reduction in cell surface area considering that endocytosis has been demonstrated to be at a complete standstill in M phase. Uptake studies using impermeant BCECF (2',7'-bis(2-carboxyethyl)-4(5)-carboxyfluorescein free acid) pH indicator and particulate neutral red dye in aqueous buffer showed preferential internalization into mitotic cells in direct contrast to expectation since interphase cells do not have arrested endocytosis. However, infolded plasma membrane ruffles and internalized extracellular material were demonstrated in prophase cells, much like those seen in interphase rounding via the induction of intracellular alkalinizations. Raised intracellular pH (pHi) is a universal and consistent finding in M phase cells. Despite cessation of small pit endocytosis, it remains possible for plasma membrane internalization to be a causal factor in the observed surface area reduction in mitotic rounding.

Cell Membrane↗
PubMed1993

Histogenetic potential of rat hind-limb interdigital tissues prior to and during the onset of programmed cell death.

The histogenetic potential of interdigital tissues isolated from the autopod of rat embryonic hind-limbs between 14.5 and 16.5 days was investigated. A wedge of tissue containing ectoderm and mesoderm was excised from between the developing digits and grafted beneath the kidney capsule of adult rats for two weeks. We have previously demonstrated that the renal capsule is an excellent site for permitting limb tissues to proliferate and differentiate (Chan et al.: J. Exp. Zool., 260:74-83, 1991). At 14.5 days, when cell death (revealed with neutral red stains) within the interdigital zone was limited to the apical ectodermal ridge (AER), the interdigital mesoderm was capable of developing into bone, cartilage, and loose connective tissue in the kidney. It was estimated that the skeletal elements occupied approximately 38% of the overall area of the grafts. In addition, the ectoderm was able to produce keratinized epithelium, hair follicles, and sebaceous glands. In 15.5 day autopod, necrosis was present both in the AER and the mesoderm between the AER and marginal sinus. Interdigital mesoderm obtained from this stage of development formed cartilage but not as extensively as that derived from 14.5 day autopod (4% as compared with 38%). Necrotic cells were present in all of the interdigital zones at 16.5 days. Ten explants were introduced into the kidney at this stage, but only 4 grafts were recovered after 2 weeks. In all cases, the explants did not produce cartilage. Only a small amount of keratinized epithelium and loose connective tissue was found. In summary the interdigital mesoderm has the potential to develop bone, cartilage, and loose connective tissue, but this ability is progressively lost during morphogenesis.

Animals↗
PubMed1994

Early development of macrophages in intact and organ cultured hearts of rat embryos.

BACKGROUND: Macrophage precursors are present early in embryonic life, being demonstrable in placental and embryonic connective tissues of rats at the neurula stage and as potential macrophages in the brain, liver, and lungs near the onset of organogenesis. We examined the development of macrophages in the heart and the possibility that they initially appear at sites of programmed cell death (apoptosis). METHODS: Precursors were recognized by the binding of peroxidase-coupled Griffonia simplicifolia isolectin B4 (GSA) on the cell membrane. Their capacity for conversion into macrophages was assayed in organ cultures; confirmation of the progeny as bona fide macrophages was obtained from their responses to particle exposure and macrophage colony-stimulating factor (M-CSF). RESULTS: GSA+cells were first seen on gestational day 12 (4 mm embryos) as 2-3 cycling, nonvacuolated cells located in cardiac tissue outside the blood vessels. This population increased to approximately 12 cells by day 14 (9 mm embryos). Two-thirds were distributed along the bulbus cordis in the jellylike endocardium and a more densely cellular connective tissue closer to the aortic arches where apoptotic sites are expected to develop. Such sites were not found in serial glycol methacrylate sections through our 14-day specimens, although in whole heart explants of this age an area of necrosis developed along the prospective line of bulbar endocardial fusion on the second day of organ culturing, and by then macrophages were fairly abundant. Organ culturing of 13-day embryonic hearts also yielded large, highly vacuolated, GSA+mononuclear phagocytes. After a few days in culture most of the macrophages migrated onto the medium where they formed a tight corona of cells about the explants. They readily ingested iron oxide particles and concentrated supravitally administered neutral red in their vacuoles. Macrophages from 14-day cultures exposed to M-CSF developed significantly larger coronas than macrophages from explants grown in serum-rich control medium (p < 0.001). In the presence of cytokines, moreover, these cardiac macrophages survived as many as 100 (92 "postnatal") days. CONCLUSIONS: Macrophage precursors first appear in embryonic rat hearts well before they are needed to clear debris generated by programmed cell death and are capable of rapid conversion into outright phagocytic cells as early as the 13th prenatal day.

Animals↗
PubMed2006

Effects of 12 days of artificial rearing on morphology of hypoglossal motoneurons innervating tongue retrusors in rat.

The purpose of this study was to examine the influence of reduced tongue activity by artificial rearing on the morphology of motoneurons innervating the extrinsic tongue retrusors. Artificially reared rat pups were fed via gastric cannula from postnatal day 3 to postnatal day 14. Artificially reared animals and dam-reared controls had cholera toxin (subunit B) conjugate of horseradish peroxidase injected into the styloglossus to label motoneurons innervating hyoglossus and styloglossus on postnatal day 13 and postnatal day 59. Following perfusion on postnatal days 14 and 60, serial transverse sections treated with tetramethyl benzidine and counterstained neutral red were used to analyze motoneuron morphology. The shorter diameter of hyoglossus motoneurons increased with age for the dam-reared but not the artificially reared group. There was a tendency for a similar pattern for styloglossus motoneurons across the two rearing groups. The changes in form factor reflected the changes in shorter diameter for both motoneuron pools. Therefore, reducing suckling activity during normal postnatal development leads to diminished motoneuron somal growth in rats. This may also be the case in premature infants necessarily fed artificially.

Animals↗
PubMed2002

Influence of 1 and 25 Hz, 1.5 mT magnetic fields on antitumor drug potency in a human adenocarcinoma cell line.

The resistance of tumor cells to antineoplastic agents is a major obstacle during cancer chemotherapy. Many authors have observed that some exposure protocols to pulsed electromagnetic fields (PEMF) can alter the efficacy of anticancer drugs; nevertheless, the observations are not clear. We have evaluated whether a group of PEMF pulses (1.5 mT peak, repeated at 1 and 25 Hz) produces alterations of drug potency on a multidrug resistant human colon adenocarcinoma (HCA) cell line, HCA-2/1(cch). The experiments were performed including (a) exposures to drug and PEMF exposure for 1 h at the same time, (b) drug exposure for 1 h, and then exposure to PEMF for the next 2 days (2 h/day). Drugs used were vincristine (VCR), mitomycin C (MMC), and cisplatin. Cell viability was measured by the neutral red stain cytotoxicity test. The results obtained were: (a) The 1 Hz PEMF increased VCR cytotoxicity (P < 0.01), exhibiting 6.1% of survival at 47.5 microg/ml, the highest dose for which sham exposed groups showed a 19.8% of survival. For MMC at 47.5 microg/ml, the % of survival changed significantly from 19.2% in sham exposed groups to 5.3% using 25 Hz (P < 0.001). Cisplatin showed a significant reduction in the % of survival (44.2-39.1%, P < 0.05) at 25 Hz and 47.5 microg/ml, and (b) Minor significant alterations were observed after nonsimultaneous exposure of cells to PEMF and drug. The data indicate that PEMF can induce modulation of cytostatic agents in HCA-2/1(cch), with an increased effect when PEMF was applied at the same time as the drug. The type of drug, dose, frequency, and duration of PEMF exposure could influence this modulation.

Adenocarcinoma↗
PubMed2003

Recognition of thymine by triazine fluorescent probe through intermolecular multiple hydrogen bonding.

In order to design a fluorescent probe with a long wavelength and multiple hydrogen bond sites for thymine, 3-(4-chloro-6-methylamino-1,3,5-triazinylamino)-7-dimethylamino-2-methylphenazine is synthesized by subsequently reacting neutral red and methylamine with cyanuric chloride. Its recognition behavior for thymine and its spectroscopic properties in different solvents are studied. The probe's fluorescence can be selectively quenched by thymine instead of guanine, indicating that fully complementary hydrogen bonding plays a key role in such recognition processes. In addition, the recognition mechanism of the probe for thymine and the bathochromic shift of its fluorescence spectra with the solvent polarity are also discussed.

Absorption↗
PubMed2003

Improved fuel cell and electrode designs for producing electricity from microbial degradation.

A new one-compartment fuel cell was composed of a rubber bunged bottle with a center-inserted anode and a window-mounted cathode containing an internal, proton-permeable porcelain layer. This fuel cell design was less expensive and more practical than the conventional two-compartment system, which requires aeration and a ferricyanide solution in the cathode compartment. Three new electrodes containing bound electron mediators including a Mn(4+)-graphite anode, a neutral red (NR) covalently linked woven graphite anode, and an Fe(3+)-graphite cathode were developed that greatly enhanced electrical energy production (i.e., microbial electron transfer) over conventional graphite electrodes. The potentials of these electrodes measured by cyclic voltametry at pH 7.0 were (in volts): +0.493 (Fe(3+)-graphite); +0.15 (Mn(4+)-graphite); and -0.53 (NR-woven graphite). The maximal electrical productivities obtained with sewage sludge as the biocatalyst and using a Mn(4+)-graphite anode and a Fe(3+)-graphite cathode were 14 mA current, 0.45 V potential, 1,750 mA/m(2) current density, and 788 mW/m(2) of power density. With Escherichia coli as the biocatalyst and using a Mn(4+)-graphite anode and a Fe(3+)-graphite cathode, the maximal electrical productivities obtained were 2.6 mA current, 0.28 V potential, 325 mA/m(2) current density, and 91 mW/m(2) of power density. These results show that the amount of electrical energy produced by microbial fuel cells can be increased 1,000-fold by incorporating electron mediators into graphite electrodes. These results also imply that sewage sludge may contain unique electrophilic microbes that transfer electrons more readily than E. coli and that microbial fuel cells using the new Mn(4+)-graphite anode and Fe(3+)-graphite cathode may have commercial utility for producing low amounts of electrical power needed in remote locations.

Biodegradation, Environmental↗
PubMed1983

The distribution of neocortical projection neurons in the locus coeruleus.

The present study was conducted to examine the spatial organization of locus coeruleus (LC) neurons that project to rat cerebral cortex. Long-Evans hooded rats received unilateral pressure injections of horseradish peroxidase (HRP) in either frontal (n = 6) or sensorimotor (n = 11) or occipital (n = 7) cortex to determine the intranuclear location of LC neurons which project to specific neocortical regions. Coronal and sagittal sections (40-100 micron) through the LC were examined by light microscopy after carrying out the tetramethyl benzidine reaction and staining with neutral red. The locations of retrogradely labeled cells were recorded on a three-dimensional biological coordinate system maintained by a computer linked to the light microscope. LC neurons labeled from cerebrocortical injections of HRP were primarily located in the ipsilateral and to a lesser extent (fewer than 5% of total labeled cells) in the contralateral nucleus. Coeruleocortical projection neurons were concentrated in the caudal three-fifths of the dorsal division of the ipsilateral LC. Within this portion of the nucleus, HRP-filled neurons were distributed so that individual groups of cells projecting to occipital or sensorimotor or frontal cortex were coarsely aligned in a dorsal to ventral array, respectively. Moreover, in the sagittal plane of the nucleus the pattern of labeling was spatially graded so that the subset of neurons projecting to the occipital cortex was displaced more caudally in the LC than the groups of cells sending axons to sensorimotor or frontal cortex. Only the frontal area of the cortex received a projection from both dorsal and ventral divisions of the ipsilateral LC. Computer-assisted analysis of the data further suggested that neocortical projection neurons in the dorsal LC are loosely organized into two groups which run rostrocaudally through the core of the caudal nucleus. The zone of labeling resulting from injections confined to the neocortical gray matter overlapped with but was not coextensive with that observed following injections into the caudate, hippocampus, and cerebellum. These results suggest that partially overlapping subsets of LC cells might independently influence separate populations of neurons within noradrenergic terminal fields of the neocortex.

Afferent Pathways↗