As from 1997, the Journal of Anatomy will be published in 8 issues per year instead of the current 6. The purpose is to reduce the time between acceptance and publication. Otherwise there will be no change in editorial policy. The Journal will continue to publish high quality papers on human and comparative anatomy and cell biology, both experimental and descriptive. Articles on experimental pathology are also acceptable if they contribute to the understanding of normal structure and function. Review articles, if topical and authoritative, are welcome. Short reports are published: these should not exceed 5 pages of printed text. Reports on isolated anatomical variations, if of sufficient interest and relevance, are now included in the Correspondence section, to which letters on matters arising out of previously published papers or on questions of general anatomical interest can be submitted.

This Anatomical Society symposium, held at University College, Cork in September 1995 was the first of its kind. The objective was to stimulate and facilitate constructive interaction between experts on topics relating to the various types of glial barrier which form partitions within the nervous system. Some of these barriers are transient and are found only during development, for example, those which define the limits of developing nuclei or fibre bundles. Others are permanent, such as those at the transitional zones which separate the CNS and PNS milieux at nerve root attachments to the neuraxis. Still others, such as glial scars, are seen only following injury when they tend to inhibit neurite regeneration. In experimental circumstances, for example following irradiation or chemical damage, glial barriers may be broken down and even relocated. This may be associated with Schwann cell invasion of the CNS and, experimentally, with Schwann cell and glial cell transplantation into demyelinated areas. Such transplantation studies are in turn related to remyelination and CNS axon regeneration and the factors which facilitate these. Twelve review lectures were given on these topics. Five articles based on these communications are reproduced here. The underlying theme was the relationship between advances in the understanding of fundamental nervous tissue biology, especially as related to glial cells, and potential developments aimed at treating CNS demyelinating diseases and achieving CNS regeneration.

This review summarises some of the major findings derived from studies using the model of a glia-depleted environment developed and characterised in this laboratory. Glial depletion is achieved by exposure of the immature rodent spinal cord to x-radiation which markedly reduces both astrocyte and oligodendrocyte populations and severely impairs myelination. This glia-depleted, hypomyelinated state presents a unique opportunity to examine aspects of spinal cord maturation in the absence of a normal glial population. An associated sequela within 2–3 wk following irradiation is the appearance of Schwann cells in the dorsal portion of the spinal cord. Characteristics of these intraspinal Schwann cells, their patterns of myelination or ensheathment, and their interrelations with the few remaining central glia have been examined. A later sequela is the development of Schwann cells in the ventral aspect of the spinal cord where they occur predominantly in the grey matter. Characteristics of these ventrally situated intraspinal Schwann cells are compared with those of Schwann cells located dorsally. Recently, injury responses have been defined in the glia-depleted spinal cord subsequent to the lesioning of dorsal spinal nerve roots. In otherwise normal animals, dorsal nerve root injury induces an astrocytic reaction within the spinal segments with which the root(s) is/are associated. Lesioning of the 4th lumbar dorsal root on the right side in irradiated or nonirradiated animals results in markedly different glial responses with little astrocytic scarring in the irradiated animals. Tracing studies reveal that these lesioned dorsal root axons regrow rather robustly into the spinal cord in irradiated but not in nonirradiated animals. To examine role(s) of glial cells in preventing this axonal regrowth, glial cells are now being added back to this glia-depleted environment through transplantation of cultured glia into the irradiated area. Transplanted astrocytes establish barrier-like arrangements within the irradiated cords and prevent axonal regrowth into the cord. Studies using other types of glial cultures (oligodendrocyte or mixed) are ongoing.

This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate into astrocytes as well oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oliodendrocyte progenitor cell line CG4) are described. These show that CG4 cells do not survive (or migrate) when transplanted into the normal adult CNS. However, if they are transplanted into CNS tissue that has previously been exposed to 40 Gy of x-irradiation then transplanted CG4 cells survive, divide and migrate over large distances. Moreover, within an x-irradiated environment, migrating transplanted CG4 cells are able to enter remotely located foci of demyelination and contribute to the remyelination of the demyelinated axons within. These studies demonstrate that although the normal adult CNS does not appear to support survival and migration of the CG4 cell line, it is possible to manipulate the environment in such a way that these nonpermissive properties of the environment can be overcome.

Schwann cells are excluded from the CNS during development by the glial limiting membrane, an area of astrocytic specialisation present at the nerve root transitional zone, and at blood vessels in the neuropil. This barrier, however, can be disrupted and, with the highly migratory nature of Schwann cells, can result in their invasion and myelination of the CNS in many pathological situations. In this paper we demonstrate that this occurs in a number of myelin mutants, including the myelin deficient (md) and taiep rats and the canine shaking (sh) pup. While it is still relatively uncommon in the rodent mutants, the sh pup shows extensive Schwann cell invasion along the neuraxis. This invasion involves the spinal cord, brain stem, and cerebellum and increases in amount and distribution with age. In situ hybridisation studies using a P0 riboprobe suggest that the likely origin of these cells in the sh pup is the nerve roots, primarily the dorsal roots. Paradoxically, Schwann cell myelination of the CNS increases with time in the sh pup despite a marked, progressive gliosis involving the glia limitans and neuropil. Thus the mechanism by which these cells migrate into the CNS through the gliosed nerve root transitional zone or from vasa nervorum remains unknown. Extensive Schwann cell CNS myelination may have therapeutic significance in human myelin disease.

Neurons cannot negotiate an elongation across the peripheral (PNS)–central nervous system (CNS) transitional zone and grow into or out of the spinal cord in the mature mammal. The astrocytic rich CNS part of the spinal nerve root is most effective in preventing regeneration even of nerve fibres from transplanted embryonic ganglion cells. Regeneration of severed nerve fibres into the spinal cord occurs when the transition zone is absent as in the immature animal. Before the establishment of a transition zone there is also new growth of neuronal processes from dorsal horn neurons distally to the injured dorsal root. Thus the experimental strategy to reestablish spinal cord to peripheral nerve connectivity has been to delete the transitional region and implant severed ventral or dorsal roots into the spinal cord. Dorsal root implantation resulted in reestablished afferent connectivity by new neuronal processes from secondary sensory neurons in the dorsal horn of the spinal cord extending into the PNS. The ability for plasticity in these cells allowed for a concurrent retention of their original rostral projection. Ventral root implantation into the spinal cord corrected deficit motor function. In a long series of experiments performed in different species, the functional restitution was demonstrated to depend on an initial regrowth of motor neuron axons through spinal cord tissue (CNS). These findings have led to the design of a new surgical strategy in cases of traumatic spinal nerve root injuries.

The management of peripheral nerve injury remains a major clinical problem. Progress in this field will almost certainly depend upon manipulating the pathophysiological processes which are triggered by traumatic injuries. One of the most important determinants of functional outcome after the reconstruction of a transected peripheral nerve is the length of the gap between proximal and distal nerve stumps. Long defects (> 2 cm) must be bridged by a suitable conduit in order to support axonal regrowth. This review examines the cellular and acellular elements which facilitate axonal regrowth and the use of acellular muscle grafts in the repair of injuries in the peripheral nervous system.

Some 30 lectins in combination with glycosidase digestion and immunohistochemistry with 5 antibodies directed against antigens of the ABO and Lewis blood group systems were used to analyse the distribution and synthesis of glycoconjugates in the epithelium of the large airways in man. Both mucous gland cells and goblet cells were labelled by 12 of 30 lectins and by the antibodies, dependent on the ABO, Lewis, and secretor status. The corresponding binding patterns of the serous gland cells differed markedly from those of goblet and mucous gland cells and in general were not dependent on the ABO, Lewis, and secretor status. After digestion with neuraminidase and fucosidase, binding of soy bean agglutinin and peanut agglutinin to goblet and mucous gland cells was increased. Binding of peanut agglutinin to serous gland cells was stronger only after the digestion with neuraminidase. Digestion with O-glycosidase after the use of neuraminidase or fucosidase resulted in a decrease of peanut agglutinin binding to goblet and mucous gland cells. The present results show that the secretory products of goblet and mucous gland cells on the one hand and those of serous cells on the other differ considerably with respect to their terminal glycosylation. The glycosyltransferases coded by genes of the ABO and Lewis blood group and secretor systems are active only in goblet and mucous gland cells, resulting in the presence of the corresponding antigens. Precursor substances of blood group antigens types 1, 2, and 3 are found only in these cell types. In serous gland cells, blood group systems do not influence the glycosylation of glycoproteins. The results of the digestion with O-glycosidase indicates the presence of O-glycosylation in mucous gland and goblet cells, but not in serous gland cells.

The organisation of the stromal cell compartment in the mouse lymph node was studied by light and electron microscopy after tissue impregnation by the zinc iodide-osmium (ZIO) method. Fibroblastic reticular cells (FRCs) represented the main stromal cell population. These cells were located both in the cortical region and in the medulla and exhibited various configurations. In the cortex, FRCs were fusiform in shape and came into close proximity with the floor of the subcapsular sinus. In the medulla, the FRCs were shaped like irregular dendritic cells which formed a complex 3-dimensional network. The FRCs surrounded vascular structures such as capillaries and/or high endothelial venules; in these instances they were organised in a discontinuous sheath-like fashion around the vessel wall. By light and electron microscopy, FRCs have been observed to come in close spatial relationship with a number of cells in the lymph node, including sinus endothelial cells, the endothelium of high endothelial venules and capillaries, various types of lymphocytes, follicular dendritic cells and interdigitating cells. These microanatomical features are consistent with the proposal that FRCs may be involved in the communicative networks between the different lymph node compartments. In particular, the FRCs may be involved in the transport of molecules from the sinus compartment to the high endothelial venules or to the distinct cell populations in the lymphoid parenchyma.

An immunocytochemical and cytochemical study has been made on the ultrastructural localisation of type III (endothelial) nitric oxide synthase, endothelin-1 and the binding sites of lectin from Bandeirea simplicifolia to the endothelium surface-associated glycoproteins in the rat left common carotid artery at 1 and 28 d after Fogarty embolectomy balloon catheter-induced injury. Controls were carotid arteries from sham operated rats. In the controls, the immunoreactivity to nitric oxide synthase-III and endothelin-1 was localised in different proportions in vascular endothelial cells (36·9%±4·3 and 7·6%±2·7, respectively); immunoreactivity was confined to the cytoplasm and the membranes of intracellular organelles and structures. In contrast, staining with lectin was localised on the luminal surface of all endothelial cells. 1 d after injury, platelets were adherent to the endothelium-denuded intima. Some of the platelets displayed immunoreactivity to nitric oxide synthase-III and endothelin-1 and were stained with lectin. 28 d after injury, a neointimal thickening of substantial size was present. Subpopulations of the regrown endothelial cells covering the luminal surface of the neointima showed positive immunoreactivity to nitric oxide synthase-III and endothelin-1 but there was a significant decrease in the proportion of nitric oxide synthase-III-containing endothelial cells (17·2%±1·9; P < 0·001) and a significant increase in the proportion of endothelin-1-containing endothelial cells (36·9%±4·7; P < 0·001) compared with the controls. Staining with lectin was associated with the cell membrane of all endothelial cells and in addition with cells located ‘deeper’ in the neointima which showed lectin-positive plasmalemma, Golgi complex and multivesicular bodies/lysosomes. In conclusion, regenerated endothelial cells of the neointima showed reduced population (2–fold) of nitric oxide synthase-III- and increased population (5–fold) endothelin-1-positive cells. The subendothelial location of some lectin-stained cells after balloon catheter injury indicates the heterogeneity of the neointima and suggests that some of these cells are involved in early angiogenesis. 24 h and 28 d after injury some platelets showed positive immunoreactivity for nitric oxide synthase-III and endothelin-1.

In this paper we examine metamerism in the vertebral column of certain mammals from the perspectives of development and adaptation. To this end we examine the patterns of metameric variation of dimensions of the neural (vertebral) canal, vertebral body and spinous process in man and inbred strains of mice. The data from inbred strains of mice indicate that variability in dimensions within a strain reflects the temporal ordering and nature of developmental influences on vertebral morphogenesis. Differences between strains parallel the within-strain findings. These findings are attributed to somatic and neural influences on morphogenesis. Comparisons between mice and man indicate that these same influences can be invoked to explain and interpret the mosaic nature of vertebral column evolution. These findings lead us to conclude that different vertebral elements and levels are subject to different interactions of evolutionary and morphogenetic influences. The study of these influences and their interactions should prove fruitful in developing an understanding of the relationship between adaptation, development, growth and function in the skeleton generally.

Morphometric analyses of the neurons and microvessels of perfusion-fixed hypogastric (HG) and 13th thoracic (T13) ganglia have been performed in male Wistar rats aged 4, 24 and 30 mo. Estimations of HG volume employing the Cavalieri principle have also been performed and showed that the size of the aged HG is increased by 42%. Routine histological staining of the ganglia with Masson's trichrome indicated that this may be due to the increased amount of interstitial connective tissue which was apparent in the aged animals. The number of neurons per unit area progressively decreased by 38% between ages 4 and 24 mo and by 16% between ages 24 and 30 mo in the HG and by 25% (4 and 24 mo) and 2% (24 and 30 mo) in the T13 ganglion. The total number of neurons in the HG however, estimated by a physical disector analysis, was constant with age. The number of microvessels per unit area, microvessel diameter, neuronal and nuclear areas did not differ significantly between the 3 age groups studied. This observed increase in ganglionic volume and decrease in neuronal packing density may be associated with changes in the extracellular matrix, in particular in glycosaminoglycans whose presence was indicated by metachromasia of the ganglia with toluidine blue. The extracellular matrix was therefore characterised using a panel of monoclonal antibodies against glycosaminoglycans and laminin. Chondroitin-6 sulphate and chondroitin-4 sulphate were present in the interstitial connective tissue, and there was an increase in the expression of both these epitopes at 24 mo, noteably surrounding neuron cell bodies. The expression of chondroitin-4 sulphate/dermatan sulphate was unchanged, thus implying a decreased expression of dermatan sulphate with age. Keratan sulphate and the native chondroitin sulphate epitopes were absent from the ganglia at both ages. Laminin expression was increased in the aged ganglia. It is therefore clear that the constituents of the extracellular matrix are not constant throughout the adult lifespan and that the extracellular matrix may influence neuronal survival in old age. This is the first report characterising age-related changes in the extracellular matrix of autonomic ganglia.

Double-label immunocytochemistry was used to investigate the colocalisation of various neuropeptides and the enzymes nitric oxide synthase (NOS) and tyrosine hydroxylase (TH) in intramural ganglia of the human male urinary bladder neck and trigone. Postmortem specimens were obtained from 7 male infants and children ranging in age from 2 mo to 3 y who had died as a result of cot death or accidental trauma. On average 60% of the intramural neurons were non-TH-immunoreactive (-IR) (i.e. presumptive cholinergic) and 40% were TH- and DbβH-IR (i.e. noradrenergic). Within the non-TH-IR population, calcitonin gene-related peptide (CGRP) was found in 65% of cells, neuropeptide Y (NPY) in 90%, nitric oxide synthase (NOS) in 45%, somatostatin (SOM) in 90%, and vasoactive intestinal polypeptide (VIP) in 40%. The corresponding values for the TH-IR neurons were CGRP (54%), NPY (70%), NOS (58%), SOM (73%) and VIP (40%). All the observed bombesin (BOM)-immunoreactivity was colocalised with TH while 90% of VIP and almost all the CGRP was colocalised with NPY. Less than 5% of neurons were immunoreactive for substance P (SP) or met-enkephalin (m-ENK) and some of these also contained TH. Varicose nerve fibres were seen in close proximity to some of the intramural neurons, the majority of such varicosities showing immunoreactivity to CGRP, VIP or TH. Less common were pericellular varicosities immunoreactive to NPY, SOM or SP. These results demonstrate the neurochemical heterogeneity of intramural neurons in the human bladder neck and provide indirect evidence for the complexity of the peripheral innervation of the human urinary bladder.

The cell population and distribution of NADPH-diaphorase positive and NOS immunoreactive intramural ganglion cells were examined on stretched whole-mount preparations of the guinea pig urinary bladder which was divided into 3 regions: base, body and dome. The results showed that the highest frequency both of NADPH-d and NOS positive neurons was observed in the bladder base. Cell counts in the whole bladder showed that the number of NADPH-d positive neurons was much more than that of NOS immunoreactive neurons. Using neuron specific enolase (NSE) positive neurons as a reference (100%), NADPH-d positive neurons accounted for 84% while NOS immunoreactive neurons only made up 45% of the total neuronal population. These results, along with previous studies on the function of nitric oxide, suggest that nitric oxide may be involved in the relaxation activity in the bladder base during micturition. The significant difference in the number of NADPH-d positive and NOS immunoreactive neurons suggests that the localisation of one enzyme does not necessarily reflect the presence of the other.

Complex arborisations occurs between the inferior ganglion of the vagus nerve and the superior cervical sympathetic ganglion (Braeucker, 1923; Fick, 1926; Siwe, 1931; Hoffman, 1957). The superior cervical sympathetic ganglion sends branches to the internal and the external carotid arteries, the inferior vagal ganglion, the superior laryngeal nerve and the cervical nerves, and provides superior cardiac and thyroid branches as well as the trunk that descends directly to the middle and inferior cervical sympathetic ganglia. There are communications between the vagus nerve (laryngeal branches) and the superior cervical sympathetic ganglion (SCSG). Cannizzaro et al. (1991) and Zerilli et al. (1994) reported abnormalities of sympathetic function among the effects of injury to the superior laryngeal nerve during thyroid surgery. The interconnections between these various nerves are therefore of clinical importance. We document here a rare example of complex communication between the vagus nerve and the SCSG in dissections of 113 adult (78 male, 35 female) Japanese cadavers. Both sides were examined in 88 cases, the right only in 18 and the left only in 7 (i.e. 201 sides in total).

The British Universities Human Embryo Database has been created by merging information from the Walmsley Collection of Human Embryos at the School of Biological and Medical Sciences, University of St Andrews and from the Boyd Collection of Human Embryos at the Department of Anatomy, University of Cambridge. The database has been made available electronically on the Internet and World Wide Web browsers can be used to implement interactive access to the information stored in the British Universities Human Embryo Database. The database can, therefore, be accessed and searched from remote sites and specific embryos can be identified in terms of their location, age, developmental stage, plane of section, staining technique, and other parameters. It is intended to add information from other similar collections in the UK as it becomes available.

A 2-year-old boy presented with a suspected urethrocutaneous fistula. He had been born at 26 wk gestation and spent 14 wk in the special care baby unit with severe respiratory problems and an episode of meningitis. He had not had a urinary catheter in situ or urinary tract infections. Bilateral inguinal hernias had been repaired. At presentation he was below the 3rd centile for height and weight but had reached all other developmental milestones.