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PubMed1995

GnRH-like immunoreactivity in the peripheral olfactory system and forebrain of Atlantic salmon (Salmo salar): a reassessment at multiple life history stages.

Neurons with gonadotropin releasing hormone-like immunoreactivity (GnRH-ir) were identified within the peripheral olfactory system of Atlantic salmon (Salmo salar) at multiple life history stages. Within the forebrain, GnRH-ir somata were found in the preoptic area and in the caudomedial olfactory bulb in a position comparable to the ganglion of the nervus terminalis of other teleosts. Somata positive for GnRH were also found throughout the rostro-caudal extent of the olfactory nerve, and clustered within the medial component of the olfactory nerve as it arises from the olfactory epithelium. Results from tract tracing experiments with horseradish peroxidase indicate that at least some cells in this cluster project to the retina, suggesting that they too are part of a terminal nerve ganglion as anatomically defined in other vertebrates. We suggest that the presence of a distinct cluster of terminal nerve ganglion cells in the immediate vicinity of the olfactory epithelium may point to a peripheral site of neuromodulatory control in the olfactory system in salmon and perhaps in other teleosts as well.

Animals↗
PubMed1999

Transregulation of erbB expression in the mouse olfactory bulb.

Previously, we have shown that erbB-3 expression is restricted to the ensheathing cells of the olfactory nerve layer, while erbB-4 is found in the periglomerular and mitral/tufted cells of the olfactory bulb and in cells coming out from the rostral migratory stream of the subependymal layer. In the present work, we have treated adult mice with zinc sulfate intranasal irrigation and analyzed erbB-3 and erbB-4 expression in the deafferented olfactory bulb. Following treatment, olfactory axons undergo degeneration, as indicated by the loss of OMP expression in the deafferented olfactory bulb. The thickness of the olfactory nerve layer is reduced, but the specific intensity of erbB-3 labeling in the remaining olfactory nerve layer is increased with respect to control. Interestingly, following deafferentation, erbB-4 immunoreactivity decreases specifically in cell types that normally make synaptic contacts with primary olfactory neurons in the glomeruli, i.e. periglomerular and mitral/tufted cells. Partial lesion of the olfactory epithelium allows regenerative axon growth of olfactory neurons to the olfactory bulb. Following olfactory axon regeneration, erbB-3 and erbB-4 immunoreactivity in the olfactory bulb is similar to control. Thus, like tyrosine hydroxylase, the down regulation of erbB-4 expression in the periglomerular cells is reversible.

Administration, Intranasal↗
PubMed1998

Ontogenic development of salmon GnRH and chicken GnRH-II systems in the brain of masu salmon (Oncorhynchus masou).

Ontogenic development of salmon gonadotropin-releasing hormone (GnRH) and chicken GnRH-II systems in masu salmon (Oncorhynchus masou) was examined. Salmon GnRH was first detected by radioimmunoassay in the embryo on day 36 after fertilization. Salmon GnRH-immunoreactive fibers were detected initially by immunocytochemistry in the vicinity of the olfactory placode of the embryo (day 36) and were distributed widely in the brain as well as in the pituitary gland of fish just after hatching (day 80). Salmon GnRH-immunoreactive neuronal somata were first detected about 6 months after fertilization in the rostroventral brain area, ranging from the olfactory nerve to the preoptic area. Salmon GnRH neuronal somata were detected earlier by in situ hybridization than by immunocytochemistry. Neuronal somata expressing salmon GnRH mRNA were first detected in the vicinity of the olfactory epithelium on day 40 and then were seen to be migrating from the olfactory epithelium, along the olfactory nerve, on day 60 and in the transitional area between olfactory nerve and olfactory bulb on day 80. In the brain, these neurons were first detected in the ventral olfactory bulb on day 80, and thereafter they were also detected in the caudal brain regions. The chicken GnRH-II system was detected later than the salmon GnRH system; chicken GnRH-II was first detected by radioimmunoassay on day 57, and chicken GnRH-II-immunoreactive fibers were first detected on day 67. Chicken GnRH-II-immunoreactive neuronal somata were not detected during the observation period. These results suggest that salmon GnRH neurons derive from the olfactory placode and then migrate into the brain and that salmon GnRH is synthesized before chicken GnRH-II.

Animals↗
PubMed1976

Anesthetic-dependent field potential interactions in the olfactory bulb.

The effect of anesthetic upon olfactory bulb field potentials evoked by paired stimuli to the lateral olfactory tract (LOT) was examined in male rats. Experiments were performed on rats anesthetized with urethane or barbiturates and on unanesthetized rats with midcollicular brain stem sections. Anesthetic doses of urethane (1.5 g/kg) produced an increse in the test response for condition-test intervals of 15-60 msec or more. With barbiturate anesthesia there was a decrease in the test response for all intershock intervals up to 150 msec. In unanesthetized rats with midbrain sections there was an increase in the test response with low intensity shock pairs and a decrease in the test response with high intensity shock pairs. Simultaneous use of both anesthetics produced either an increase or a decrease in the test response, depending upon the relative doses and upon the stimulus intensity. Paired stimuli to the olfactory nerve produced results similar to those with LOT stimulation. Augmentation of the olfactory bulb field potential produced by paired olfactory nerve shocks was not abolished by lesions which sectioned the LOT and produced extensive damage of the anterior olfactory nucleus.

Animals↗
PubMed1998

Retinoid signaling distinguishes a subpopulation of olfactory receptor neurons in the developing and adult mouse.

We asked whether retinoic acid (RA) influences olfactory receptor neurons (ORNs) in the developing and mature mouse olfactory epithelium (oe). The distribution of retinoid receptors and binding proteins in the oe changes between embryonic days 11.5 and 13.5, the period when ORNs first differentiate and send axons into the nascent olfactory nerve. Coincident with this change, RA, which is produced in the frontonasal mesenchyme at these ages, begins to activate gene expression in a bilaterally symmetric subset of ORNs in the dorsolateral oe, as judged by the expression of an RA-responsive transgene. Axons from these RA-activated ORNs are segregated in the olfactory nerve as it extends through the frontonasal mesenchyme toward the forebrain. In vitro, RA potentiates ORN neurite growth on laminin, which, in the embryo, is found in a stripe of frontonasal mesenchyme directly associated with the olfactory nerve. RA does not modify growth on fibronectin, type IV collagen, or L1, which olfactory axons encounter in different regions of the territory between the olfactory epithelium and the brain. The pattern of RA-mediated transcriptional activation and axon segregation persists in early postnatal mice, and RA signaling can be recognized in a subset of adult ORNs in the dorsolateral oe. Thus, RA-mediated gene expression distinguishes a subpopulation of ORNs in a distinct region of the oe during the early development of the olfactory pathway, and may influence differentiation and axonal projections of ORNs in this region throughout life.

Animals↗
PubMed1994

Changes in expression of the low affinity receptor for neurotrophins, p75NGFR, in the regenerating olfactory system.

We have disrupted the integrity of the rat olfactory neuroepithelium using intranasally applied TX-100, a procedure known to reversibly eliminate the sensory neuron input from the neuroeithelium to the olfactory bulb [Margolis et al. (1974) Denervation in the primary olfactory pathway of mice: biochemical and morphological effects. Brain Res. 81, 469-483]. One week after TX-100 exposure, we observed a disruption of the pseudo-stratified organization of the neuroepithelium which was accompanied by a 60% reduction in neuroepithelial width, compared to saline-treated controls. Full recovery of the neuroepithelium was not observed until 16 weeks post-lesion. During this post-lesion period, we monitored the expression of the low affinity receptor for neurotrophins, p75NGFR, in the olfactory bulb of saline- and TX-100-treated animals, using the monoclonal antibody, MAb192. In saline-treated animals, p75NGFR-immunoreactivity (p75NGFR-ir) was localized to individual glomeruli in the olfactory bulb, with little or undetectable p75NGFR-ir in the olfactory nerve layer. We have previously reported that pre-lesioned levels of p75NGFR-ir in the glomerular layer were dramatically reduced while an induction of p75NGFR-ir was observed in the olfactory nerve layer, one and two weeks after intranasal exposure to TX-100 [Turner & Perez-Polo (1992) Regulation of the low affinity receptor for nerve growth factor, p75NGFR, in the olfactory system of neonatal and adult rat. Int. J. Devl Neurosci. 10, 343-359]. In this paper, we demonstrate that this previously reported reduction in glomerular p75NGFR-ir took 16 weeks to fully recover and was, thus, coincident with the post-lesion recovery of the neuroepithelium. In the olfactory nerve layer, the return of p75NGFR-ir to pre-lesioned levels took only four weeks. No changes in neuroepithelial width and integrity or alterations in p75NGFR-ir in the olfactory bulb were observed in saline-treated animals. Thus, the TX-100-induced removal of the peripheral input to the olfactory bulb resulted in a reversible change in expression of p75NGFR-ir in the bulb. We believe that these changes are a reflection of the regenerative capacity of the olfactory system.

Animals↗
PubMed1998

Influence of olfactory innervation on neurogenesis in the developing olfactory bulb of the frog, Xenopus laevis.

Previous research on development of the Xenopus olfactory bulb from our laboratory has shown that mitral cells begin to differentiate after olfactory axons make contact with the olfactory bulb, and the number of olfactory axons is correlated with the number of mitral cells throughout development. In embryos, removal of all afferent innervation before the mitral cells begin to differentiate results in a failure of the bulb to form; removal of half the olfactory axons, results in development of half the normal number of mitral cells. At larval stages, transection of the olfactory nerve results in a decrease in the number of neurons in the olfactory bulb. Thus, the olfactory axons play a major role in stimulating or maintaining development of the olfactory bulb neurons. Since we have found that neurogenesis in the bulb continues through metamorphosis, the goal of the current study was to determine whether olfactory axons influence cell genesis and/or neuronal maturation in the larval olfactory bulb. To study cell genesis, we cut the olfactory nerves, and 6 days later, injected the animals with [3H]thymidine. After 6 hr, the animals were killed and the tissue was processed for autoradiography. The number of labeled cells in the ventricular zone of the olfactory bulb was determined in every fifth section through the bulb in control and experimental animals. There was no statistical difference (Mann-Whitney rank sum test) in the number of labeled ventricular cells between controls and experimentals. Thus, olfactory axon innervation does not appear to play a role in precursor cell division during larval development. To study the influence of olfactory axon innervation on the ability of newly generated neurons to mature, we followed the same procedures. However, the animals were killed 21 days after the [3H]thymidine injection. The results from this experiment showed that there are many fewer labeled mitral cells in the experimental animals at 21 days. Together these results suggest that sensory deafferentation influences mitral cell differentiation or survival even during late stages of larval development.

Animals↗
PubMed1993

Interbulbar reciprocal inhibition in frog olfaction.

Frogs were submitted in acute experiments to electrical stimulation of both ipsi- and contralateral homologous olfactory nerve bundles subserving the dorsal olfactory mucosae. Mitral layer responses on one side were recorded. When both stimulations were given at different onset times and equal intensity, the ipsilateral mitral layer response fell to a sharp minimum of 42% when the contralateral stimulation was given 25 ms before the ipsilateral one. When both stimuli were adjusted for maximal temporal inhibition and the intensity of the contralateral stimulation was varied, the amplitude of the ipsilateral response decreased as the intensity of the contralateral stimulation increased until intensity equalization was obtained. This interbulbar inhibition was suppressed either by sagittal transection through the interbulbar adhesion or local infusion of bicuculline in the ipsilateral olfactory bulb. It was unaffected by transection of habenular commissure. These findings suggest first, that the neuroreceptors located in the dorsal olfactory mucosae project to both olfactory bulbs, and second, that it exists at mitral layer level of the frog, a reciprocal inhibition which can subserve frog orientation towards proximal odour source.

Animals↗
PubMed2002

Multiple axon guidance cues establish the olfactory topographic map: how do these cues interact?

Each primary olfactory neuron stochastically expresses one of approximately 1000 odorant receptors. The total population of these neurons therefore consists of approximately 1,000 distinct subpopulations, each of which are mosaically dispersed throughout one of four semi-annular zones in the nasal cavity. The axons of these different subpopulations are initially intermingled within the olfactory nerve. However, upon reaching the olfactory bulb, they sort out and converge so that axons expressing the same odorant receptor typically target one or two glomeruli. The spatial location of each of these approximately 1800 glomeruli are topographically-fixed in the olfactory bulb and are invariant from animal to animal. Thus, while odorant receptors are expressed mosaically by neurons throughout the olfactory neuroepithelium their axons sort out, converge and target the same glomerulus within the olfactory bulb. How is such precise and reproducible topographic targeting generated? While some of the mechanisms governing the growth cone guidance of olfactory sensory neurons are understood, the cues responsible for homing axons to their target site remain elusive.

Animals↗
PubMed1993

Cell adhesion molecules and the migration of LHRH neurons during development.

During embryogenesis, LHRH neurons arise in the olfactory epithelium, migrate along the olfactory nerve, and enter the forebrain. We have examined the distribution of several cell adhesion molecules (CAMs) in the developing chick olfactory system and brain to determine whether differential distributions of these adhesion molecules might be important in pathway choices made by migrating LHRH neurons. Single- and double-label immunocytochemical studies indicated that high levels of N-CAM and N-cadherin were expressed throughout the olfactory epithelium and not restricted to the medial half of the olfactory epithelium where most of the LHRH neurons originate. Further, high levels of N-CAM, Ng-CAM, and N-cadherin were uniformly expressed throughout the entire olfactory nerve while migrating LHRH neurons were confined to the medial half of the nerve. However, once LHRH neurons reach the brain, they migrate dorsally and caudally, tangential to the medial surface of the forebrain, along a region enriched in N-CAM and Ng-CAM. After this first stage of migration within the brain, LHRH neurons migrate laterally. At this stage, there is no correlation between the intensity of N-CAM and Ng-CAM immunostaining and the location of LHRH neurons. These results suggest that N-CAM, Ng-CAM, and N-cadherin do not play a guiding role in LHRH neuronal migration through the olfactory epithelium and olfactory nerve but that migrating LHRH neurons may follow a "CAM-trail" of N-CAM and Ng-CAM along the medial surface of the forebrain.

Animals↗
PubMed1991

Evaluation of projection patterns in the primary olfactory system of rainbow trout.

Topographic projections are important for coding sensory information in the visual, auditory, and somatosensory systems but are of uncertain importance in the coding of olfactory information. We searched for topographic projections between olfactory receptor cells and the olfactory bulb of the rainbow trout Oncorhynchus mykiss. Anterograde axonal tracing with HRP revealed that the olfactory axons arising from discrete regions of the olfactory epithelium travel together within the olfactory nerve. The abrupt resorting and redistribution of these axons at the interface between the olfactory nerve and olfactory bulb imply that local cues control and organize axonal projections. The sites of termination of HRP-labeled axons in the glomerular layer could not be predicted from the location of their cell bodies in the periphery. Retrograde tracing with fluorescently labeled latex beads, injected into glomerular subregions as small as 1% of the total glomerular volume, labeled receptor cells dispersed throughout the olfactory epithelium. The distributions of labeled receptor cells were uncorrelated with the bulbar injection sites. Double-labeling experiments revealed that even widely separated sites in the glomerular layer receive axons from comingled populations of receptor cells. Hence, the evidence indicates that the spatial arrangement of olfactory receptor cells in the epithelium is not preserved in the termination of their axons in the olfactory bulb. We conclude that the primary olfactory in trout lacks point-to-point or regionally topographic organization and that the entire extent of the olfactory epithelium contributes axons to each region of the glomerular layer.

Animals↗
PubMedDate not supplied

Response of the olfactory bulb antioxidant system following diethyldithiocarbamate (DDTC) administration in rats.

This study was designed in order to evaluate alterations in the reactive oxygen species (ROS) scavenging system in olfactory bulb, dorsal neocortex and cerebellum for 6 weeks following a single subcutaneous dose (600 mg kg-1) of diethyldithiocarbamate (DDTC) to rats. A single dose of DDTC caused substantial damage to the olfactory epithelium and degeneration within the olfactory bulb. The epithelium regenerates, followed by regeneration in the olfactory bulb. The mean olfactory bulb weight decreased significantly 3 days after DDTC administration and gradually recovered to control values in 6 weeks. The DDTC-induced lesion of the olfactory nerve resulted in significant changes in glutathione (GSH) and antioxidant enzyme activities in olfactory bulb. In contrast, no significant changes were found in either cerebellum or dorsal neocortex. These observations indicate that a single dose of DDTC selectively affected the ROS scavenging system of the olfactory bulb. Moreover, these changes persisted for at least 6 weeks, which includes regeneration and synaptogenesis. Olfactory bulb GSH concentrations decreased significantly by 47 +/- 4%, glutathione reductase activity decreased by 18 +/- 3% and catalase activity increased by 27 +/- 7% over the 6 weeks. Superoxide dismutase activity decreased significantly in olfactory bulb of rats by 32 +/- 6% at 3 days following the lesion and then recovered and increased by 38 +/- 3% at 3 weeks. Olfactory bulb malondialdehyde concentrations were elevated (298 +/- 67%) throughout the post-lesion survival period, although this change did not reach the stringent statistical significance level required in this study. These data suggest that increased ROS flux perturbs the olfactory bulb antioxidant defense system during olfactory nerve regeneration.

Animals↗
PubMed1991

Subsets of olfactory and vomeronasal sensory epithelial cells and axons revealed by monoclonal antibodies to carbohydrate antigens.

Cell surface glycoconjugates are believed to play an important role in cell-cell interactions during development of CNS pathways. In order to identify developmentally regulated glycoconjugates in the nervous system, monoclonal antibodies were raised and selected for reactivity with carbohydrate antigens. Three monoclonal antibodies were identified, each of which reacts with a defined carbohydrate epitope and reveals a unique pattern of immunoreactivity within the olfactory sensory epithelia, vomeronasal and olfactory nerves and their terminal regions in rats. Antibody CC1 reacts with a globoside-like glycolipid which contains a terminal N-acetylgalactosamine residue. CC1-immunoreactivity is present in just the vomeronasal organ, vomeronasal nerve and in the rostral half of the accessory olfactory bulb. Antibody CC2 reacts with a complex glycolipid which contains a branched chain oligosaccharide terminating with alpha-galactose and alpha-fucose. CC2-immunoreactivity is seen throughout the vomeronasal organ, in dorsomedial regions of the olfactory sensory epithelia, in the vomeronasal and olfactory nerves, the accessory olfactory bulb and dorsomedial glomeruli of the main olfactory bulb. Antibody 1B2 reacts with lacto-N-glycosyl ceramides. 1B2-immunoreactivity is highest at the luminal surfaces of receptor cells throughout the vomeronasal organ and in portions of the olfactory sensory epithelia. 1B2 is also expressed on the surface of a subset of receptor cell bodies, their dendrites and the proximal region of their axons in dorsomedial regions of the main olfactory epithelium.

Animals↗
PubMed1993

Nerve growth factor (NGF) and its receptor in rat olfactory epithelium.

Nerve Growth Factor (NGF) is a bioactive protein that plays an important role in the genesis, differentiation, growth, maintenance and aging of the central and peripheral nervous systems. The purpose of this study was to explore the significance of NGF in the turnover, regeneration and maintenance of the olfactory epithelium. We tried to detect NGF and NGF-receptor in the olfactory epithelium of young and mature rats with an immunohistochemical technique. Immunoreactivity to NGF and NGF-receptor was detected in all specimens of olfactory epithelium. Immunoreactivity to NGF was positive in the olfactory nerve cells, especially in the cytoplasm and dendrites, in the basal cell layer, and on fibers piercing the olfactory epithelium. Immunoreactivity to NGF-receptor was positive in the basal cell layer and on fibers piercing the olfactory epithelium. These results suggest that NGF plays a role in the maintenance of olfactory nerve cells, and in the differentiation from the basal cell to the mature olfactory nerve cell, in both the young and the mature rat. In addition, the differences in the density of immunoreactive cells between different parts of the olfactory epithelium support the concept of an active and a quiescent zone in olfactory epithelium turnover.

Aging↗
PubMed2000

Structure of the olfactory bulb in tadpoles of Xenopus laevis.

The structure of the olfactory bulb in tadpoles of Xenopus laevis (stages 54-56) was studied using axon tracing (with biocytin or low-weight dextran) and immunocytochemical techniques. Filling the olfactory nerve with biocytin made the nerve layer and the glomeruli visible. Dye injections into the glomerular layer labeled the lateral olfactory tract. Vice versa, dye injections into the lateral olfactory tract made mitral cells and their glomerular branching patterns visible. Anti-GABA antiserum stained periglomerular and granule cells, while the olfactory nerve and mitral cells were labeled by antiglutamate antiserum. We describe the layering, the numbers of cells and glomeruli, and their localization in both the main and the accessory olfactory bulb.

Animals↗
PubMed1998

Expression of the low affinity neurotrophin receptor, P75NGFR, in the rat forebrain, following unilateral bulbectomy.

It has been hypothesized that the main olfactory bulb, with its relatively rich source of neurotrophins, may provide trophic support for neurons that project to the bulb. We monitored expression of the common, low affinity receptor for neurotrophins, p75NGFR, in the olfactory bulb and basal forebrain of unilaterally bulbectomized and sham-treated rats, 1-16 weeks post-surgery, using the monoclonal antibody MAb192. An induction of p75NGFR-immunoreactivity was observed in both the glomerular and olfactory nerve layers of the right, contralateral main olfactory bulb of lesioned animals. The naturally occurring regeneration taking place in the olfactory neuroepithelium is known to be altered by olfactory bulbectomy, with subsequent changes in the sensory input to the remaining bulb. These changes in expression of p75NGFR in the olfactory bulb support the hypothesis we have developed in previous papers, that changes in the extent of the peripheral input from the olfactory neuroepithelium to the main olfactory bulb regulate p75NGFR expression in both the glomerular and the olfactory nerve layers. Expression of p75NGFR in the basal forebrain of bulbectomized animals was found to be no different than sham-treated controls and does not support the hypothesis that the olfactory bulb provides trophic support to this region of the central nervous system.

Animals↗
PubMed2000

Olfactory sensitivity to changes in environmental [Ca(2+)] in the marine teleost Sparus aurata.

Estuarine and/or migratory teleosts may experience large and rapid changes in external [Ca(2+)]. Previous studies have largely centred on the physiological mechanisms that maintain a constant plasma [Ca(2+)] in the face of such external fluctuations, but little work has been directed to examining how these changes may originally be detected. We present evidence that the olfactory system of the gilthead seabream (Sparus aurata) is highly sensitive to reductions in environmental [Ca(2+)] and suggest a possible mechanism by which this may be mediated. Multi-unit extracellular recordings were made from the olfactory nerve of Sparus aurata while the [Ca(2+)] of artificial sea water flowing over the olfactory epithelium was varied from 10 to 0 mmol l(-)(1). Reductions in [Ca(2+)] caused a large, non-accommodating increase in the firing rate of the olfactory nerve (apparent IC(50)=1.67+/-0.26 mmol l(-)(1), apparent Hill coefficient=-1.22+/-0.14; means +/- s.e.m., N=6). This response was not due to the concomitant reduction in osmolality and was specific for Ca(2+). During continuous exposure of the olfactory epithelium to Ca(2+)-free sea water, the apparent IC(50) and Hill coefficient in response to increases in [Ca(2+)] were 0.48+/-0.14 mmol l(-)(1) and -0.76+/-0.16 (means +/- s.e.m., N=6), respectively, suggesting an adaptation of the Ca(2+)-sensing system to low-[Ca(2+)] environments. Ca(2+) is intimately involved in signal transduction in the olfactory receptor neurones, but our data support a true olfactory response, rather than a non-specific effect to lowering of external [Ca(2+)]. The absence of Ca(2+) from sea water only partially and temporarily blunted the olfactory response to the odorant l-serine; the response amplitude recovered to control levels within 20 min. This suggests that the olfactory system in general is able to adapt to low-[Ca(2+)] environments. We suggest that the Ca(2+ )sensitivity is mediated by an extracellular Ca(2+)-sensing receptor similar to the recently characterized mammalian Ca(2+)-sensing receptor.

Action Potentials↗
PubMed1994

The nasal route of cerebrospinal fluid drainage in man. A light-microscope study.

The drainage routes from the subarachnoid space to the nasal mucosa were investigated in autopsy material. Indian ink, applied post-mortem to the olfactory groove, promptly filled the perineurial spaces around the olfactory nerve branches in the dura, the lamina cribrosa and the submucosal tissue in the nose. In a case of recent subarachnoid haemorrhage, the perineurial spaces even around the most distal olfactory nerve branches were congested with blood and there was an abundant accumulation of red corpuscles in the apical part of the nasal mucosa. Iron-containing pigment was found in the perineurial spaces of proximal and distal olfactory nerve branches as well as in the nasal mucosal stroma in cases with older haemorrhagic lesions. The findings show that the perineurial spaces provide an efficient drainage route from the subarachnoid space to the nasal mucosa in cases with haemorrhagic cerebral lesions. A complementary drainage route for the cerebrospinal fluid was indicated by the presence of indian ink, red corpuscles and iron pigment in arachnoid villi, which penetrated the lamina cribrosa and ended in the nasal submucosal tissue. Iron in the deep cervical lymph nodes should not be taken as evidence of transport from the CNS, since iron pigment was also found in cases without intracranial haemorrhage.

Adult↗