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PubMed2001

[The role of transplanted astrocytes for the regeneration of CNS axons].

Long tract axons in the mammalian CNS do not normally regenerate for appreciable distance after they transected. But we reported transplantation of Schwann cells(SCs) or olfactory ensheathing cells induced regeneration of transected rat dorsal column (DC) axons and improved the conduction. Scar formation(gliosis), for which astrocytes(ACs) play an important role, may be one of strong and physical barriers for the regeneration of CNS axon. Oligodendrocyte and myelin associated protein or products also inhibit the regeneration of the axons, as chemical barriers. To investigate how effective the promotion or the reduction of scar or myelin formation may be for axonal regeneration, we transplanted AC into transected DCs, or radiated(X-ray) the DCs, and compared to normal DCs or regenerated DCs following by SC transplantation. DCs of adult rats were transected at Th 11 and transplanted with SCs(6 x 10(4)) of adult rats or ACs(6 x 10(4)) of neonatal rats. Five to six weeks later, the spinal cords were removed and pinned in a recording chamber, and compound action potentials (CAPs) along the DC through the transected lesion were recorded, to investigate conduction properties(conduction velocity and response after high frequency stimulations). Following transplantation of SCs or ACs, histological examination revealed regenerated axons with SC-like patterns of remyelination in transected DCs. X-ray irradiation did not enhance the regeneration of DC axons. SC transplantation improved the conduction properties of transected DCs and increased the number of regenerated axons, compared to transected DCs without cell transplantation. AC transplantation resulted in improvement of the conduction properties, but the number of regenerated axons was similar to that of transected DCs without the transplantation. X-ray irradiation (40 Gy) three days before DC transection and AC transplantation prevented the electrophysiological continuity of axons through the transected lesion. This evidence revealed that AC transplantation secondarily enhanced the regeneration of axons, probably endogeneous SCs of dorsal roots migrated into the transected lesion and enhanced the axonal regeneration.

Animals↗
PubMed2001

The nigrostriatal pathway in the rat: A single-axon study of the relationship between dorsal and ventral tier nigral neurons and the striosome/matrix striatal compartments.

Axons from dorsal/ventral tiers of substantia nigra pars compacta (SNc), ventral tegmental area (VTA), and retrorubral field (RRF) were traced after injecting their cell body with biotinylated dextran amine. Fifty-three single axons were reconstructed from serial sagittal sections with a camera lucida, and mu-opiate receptor immunostaining served to differentiate the striosome/matrix striatal compartments. Most dorsal tier SNc axons terminate within the matrix of the dorsal striatum, but their patterns of arborization vary markedly; some axons innervate one specific matriceal area, whereas others arborize in multiple discontinuous loci. Some dorsal tier SNc axons also project to both striosomes and matrix. Other dorsal tier SNc axons, as well as VTA axons, innervate the ventral striatum and send collaterals to striosomes lying ventrally in the dorsal striatum or to the ventral sector of the subcallosal streak (SS). Ventral tier SNc axons arborize principally in striosomes, but some ramify in both compartments or in striosomes and the SS. Ventral tier neurons that form deep clusters in substantia nigra pars reticulata innervate principally the matrix and the SS. The amygdala and ventral pallidum receive secondary collaterals from striatal axons of dorsal/ventral tier neurons or RRF neurons. The subthalamic nucleus receives collaterals from striatal axons of SNc clustered neurons, whereas the globus pallidus gets collaterals from striatal axons of dorsal/ventral tier SNc neurons. These findings reveal that the nigrostriatal pathway is composed of several neuronal subsystems, each endowed with a widely distributed axonal arborization that allows them to exert a multifaceted influence on striatal and/or extrastriatal structures.

Animals↗
PubMed2003

Slit2 guides both precrossing and postcrossing callosal axons at the midline in vivo.

Commissural axons generally cross the midline only once. In the Drosophila nerve cord and mouse spinal cord, commissural axons are guided by Slit only after they cross the midline, where Slit prevents these axons from recrossing the midline. In the developing corpus callosum, Slit2 expressed by the glial wedge guides callosal axons before they cross the midline, as they approach the corticoseptal boundary. These data highlighted a potential difference between the role of Slit2 in guiding commissural axons in the brain compared with the spinal cord. Here, we investigate whether Slit2 also guides callosal axons after they cross the midline. Because such questions cannot be addressed in conventional gene knock-out animals, we used in utero injections of antisense oligonucleotides to specifically deplete Slit2 on only one side of the brain. We used this technique together with a novel in vitro assay of hemisected brain slices to specifically analyze postcrossing callosal axons. We find that in the brain, unlike the spinal cord, Slit2 mediates both precrossing and postcrossing axonal guidance. Depletion of Slit2 on one side of the brain causes axons to defasciculate and, in some cases, to aberrantly enter the septum. Because these axons do not recross the midline, we conclude that the principle function of Slit2 at the cortical midline may be to channel the axons along the correct path and possibly repel them away from the midline. We find no evidence that Slit2 prevents axons from recrossing the midline in the brain.

Animals↗
PubMed1991

Myelin sheath survival following axonal degeneration in doubly myelinated nerve fibers.

Axonal contact plays a critical role in initiating myelin formation by Schwann cells. However, recent studies of "double myelination" have indicated that myelin maintenance continues in Schwann cells completely displaced from physical contact with the axon. This raises the possibility either that diffusible trophic factors are produced by the axon, or that the axon is not required for myelin maintenance by these displaced Schwann cells. To test these hypotheses, the axons involved in double myelination in the mouse superior cervical ganglion (SCG) were transected surgically by a transganglionic lesion. The inferior pole of the SCG was resected to limit axonal regeneration. This method produced a typical Wallerian pattern of degeneration in the superior pole, without compromising the blood supply or introducing nonspecific trauma. EM analysis at 1 and 5 d postoperatively showed that initially the axon degenerated, followed by breakdown of the inner myelin sheath. In those configurations where the outer Schwann cell was only partly displaced from the axon, the outer myelin sheath degenerated simultaneously. However, in completely displaced internodes the outer sheath survived degeneration of the axon and inner sheath. Outer internodes remained intact for at least 5 weeks after transection (the longest time point in this study), at which time they enclosed reorganized processes of the inner Schwann cells, their basal lamina, and numerous collagen fibrils. Axonal regeneration within surviving outer internodes was rare and was characterized by the development of typical Remak ensheathment by the inner Schwann cells. We conclude that in the mouse SCG, myelin maintenance does not depend on the continued presence of the axon. These data suggest further that myelin breakdown in Wallerian degeneration may be initiated by mechanisms other than absence of a viable axon.

Animals↗
PubMed1984

Postnatal maturation of cerebellar mossy and climbing fibers: transient expression of dual features on single axons.

We have studied the form and fine structure of developing afferent axons in postnatal mouse cerebellum, before and during the formation of synaptic connections. In slices of fresh brain, bundles of axons were injected with horseradish peroxidase (HRP), and individual axons were examined in the light and electron microscopes. At birth, before formation of cortical layers, axons with growing tips are rare in the peduncular tracts but instead ramify throughout the cerebellar anlage. All axons have similar structures; they branch infrequently and terminate in bud-like tips and/or small growth cones. Growth cones contain small and large vesicles in the flank and small vesicles in filopodia. Typical mossy and climbing fiber branching patterns and bouton shapes are recognizable after postnatal day (P) 5, even though fibers are still intermingled in a plexus beneath the newly formed Purkinje cell layer. Climbing fiber-like axon arbors are highly branched and covered with small foliate growing tips that contact Purkinje cells. Mossy fiber-like branches have large irregular expansions that give rise to long filopodia and resemble growth cones seen in vitro. The flanks of these growth cones contact granule cell dendrites and form glomeruli typical of mossy fibers, whereas the filopodia make primitive contacts or are associated with coated vesicles in adjacent profiles. A novel finding is the occurrence during the second postnatal week of many single axons that simultaneously have the morphology and synaptic connections of both climbing and mossy fibers. These "combination" axons have some branches that extend into the granule cell layer and others that enter the Purkinje cell layer, with the shape and synaptic connections of terminals on each branch type corresponding to the respective layer. Climbing fiber-like branches, including those on combination fibers, extend over several adjacent Purkinje cells. Combination fibers are rare in late postnatal or adult stages. These results suggest that long after arrival in the cerebellum, afferent axons have similar elementary forms and overlap in their projections. Mature axonal forms are not exhibited until cellular layers develop. During a limited period of postnatal maturation, some axons have dual morphologies and synaptic relations with appropriate and inappropriate partners. These aspects of cerebellar axonal development, particularly the transient exuberant branching onto two types of target cells, offer a valuable opportunity to examine, in developing cerebellum, the sorting out of afferents and the formation of specific synaptic connections.

Animals↗
PubMed1994

Mechanical tension as a regulator of axonal development.

We review studies from our laboratory over the last 6 years that indicate the mechanical tension on the axons of cultured neurons is a regulator and stimulator of axonal elongation and retraction. Using calibrated glass needles to measure or apply tension, we have accumulated direct evidence for tension as a regulator of four different phases of axonal development: 1) axonal initiation; 2) growth cone-mediated elongation; 3) growth after the growth cone reaches its target; and 4) axonal retraction. Our results can be summarized by a model in which tension levels behave as a three position controller, like a double-pole, double-throw electric switch. The three settings of this switch are separated by tension thresholds: 1) Above the upper threshold, tension acts as a stimulator for axonal elongation and initiation. The growth rate of the neurite is directly proportional to the magnitude of tension on the neurite. Similar levels of tension can initiate neurites de novo from chick sensory neurons. These tension-induced axons are normal in their axial array of microtubules and in the development of a motile growth cone. Under normal conditions of growth, our evidence supports the notion that the growth cone stimulates axonal elongation by acting as a tractor, pulling on the neurite; 2) The "switch" also has a setting for axonal retraction, which occurs at tension magnitudes below some different, lower tension threshold. Our evidence indicates that such axonal retraction involves active force generation by the neurite shaft; and 3) Between the two thresholds, the switch is in a neutral position and the neurite behaves passively as a viscoelastic solid. That is, the neurite stretches in response to tension but there is no true growth, i.e. no microtubule assembly or membrane addition etc. Thus, it seems tension can be regarded as a kind of "second messenger" whose level regulates axonal development. The mechanism of action of developmental neurotoxicants may be to alter the production of, or the sensitivity to, tension. At the least, this evidence that mechanical force regulates axonal growth provides a new avenue of investigation into neurotoxic mechanisms.

Animals↗
PubMed1994

Diffuse axonal injury in craniocerebral trauma. A comparative histologic and immunohistochemical study.

Axonal swellings are the major histologic hallmark of diffuse axonal injury in craniocerebral trauma. In this study, we compared conventional histologic and immunohistochemical methods for demonstrating axonal swellings in 11 cases of head trauma. Brain regions known to be susceptible to diffuse axonal injury were examined with conventional hematoxylin-eosin and silver (Bodian) stains and immunohistochemical markers for neurofilaments, ubiquitin, and tau and beta/A4-amyloid. A quantitative assessment of the axonal swellings visualized with each stain was made. In all but one case, axonal swellings were identified with the hematoxylin-eosin stain. By contrast, both the silver and neurofilament stains demonstrated fewer axonal swellings and were often difficult to interpret due to staining of normal axons. In the majority of cases, the ubiquitin stain revealed the greatest number of axonal swellings. Axonal swellings were not visualized with the tau or beta/A4-amyloid antibodies. We conclude that the standard hematoxylin-eosin stain remains a reliable method for the detection of axonal swellings in craniocerebral trauma and is superior to the Bodian and neurofilament stains. Identification and quantitative assessment of diffuse axonal injury is aided by the use of immunocytochemical staining for ubiquitin.

Adolescent↗
PubMed1996

The behavior of optic axons on substrate gradients of retinal basal lamina proteins and merosin.

To study the behavior of optic axons to continuously changing concentrations of their substrate, explants from embryonic retina were placed across gradients of retinal basal lamina proteins and merosin. The following growth patterns of axons in response to the substrate gradients were found: (1) Axons that grew up gradients, i.e., from low to high substrate concentrations, became longer and less fasciculated with increasing concentration of the substrate. On shallow basal lamina gradients, the axons also showed a directional response that resulted in guidance to higher substrate concentrations. (2) Axons that grew down gradients, i.e., from high to low substrate concentrations, became shorter and more fasciculated with decreasing concentrations of the substrate. On gradients of merosin, a significant alteration in the axonal growth direction toward higher substrate concentrations was detected. Axons heading down gradients never U turned to higher substrate concentrations. (3) Axons confronted with discontinuous substrates were confined to the borders of the substrate exclusively, whereas axons confronted with substrate gradients were able to cross into the territory beyond the substrate. (4) The growth patterns of axons on substrate gradients of basal lamina proteins and merosin were similar but not identical, indicating that axons may respond to substrate gradients dependent on its chemical composition. The present results show that substrate gradients can regulate length and fasciculation of neurites and have a limited capability to direct axons to higher substrate concentrations.

Animals↗
PubMed1996

Oligodendroglia regulate the regional expansion of axon caliber and local accumulation of neurofilaments during development independently of myelin formation.

Axon caliber may be influenced by intrinsic neuronal factors and extrinsic factors related to myelination. To understand these extrinsic influences, we studied how axon-caliber expansion is related to changes in neurofilament and microtubule organization as axons of retinal ganglion cells interact with oligodendroglia and become myelinated during normal mouse brain development. Caliber expanded and neurofilaments accumulated only along regions of the axon invested with oligodendroglia. Very proximal portions of axons within a region of the optic nerve from which oligodendrocytes are excluded remained unchanged. More distally, these axons rapidly expanded an average of fourfold as soon as they were recruited to become myelinated between postnatal days 9 and 120. Unmyelinated axons remained unchanged. Axons ensheathed by oligodendroglial processes, but not yet myelinated, were intermediate in caliber and neurofilament number. That oligodendrocytes can trigger regional caliber expansion in the absence of myelin was confirmed using three strains of mice with different mutations that prevent myelin formation but allow wrapping of some axons by oligodendroglial processes. Unmyelinated axons persistently wrapped by oligodendrocytes showed full axon caliber expansion, neurofilament accumulation, and appropriately increased lateral spacing between neurofilaments. Thus, signals from oligodendrocytes, independent of myelin formation, are sufficient to induce full axon radial growth primarily by triggering local accumulation and reorganization of the neurofilament network.

Aging↗
PubMed1996

Localization and active transport of mRNA in axons of sympathetic neurons in culture.

In neurons, the establishment and maintenance of distinct somatic, dendritic, and axonal domains has long been known to rely on regulated traffic of organelles and proteins. More recently, the local targeting of specific mRNAs has also been demonstrated, at least in dendrites, to provide a local supply of specific proteins. Here we set out to test directly for the presence of mRNA in axons of cultured chick sympathetic neurons, to examine their distribution during axonal outgrowth, to determine the reliance of this distribution on specific cytoskeletal elements, and to assess whether the axonal and somatic mRNA complements differ. Using fluorescent in situ hybridization, we found that sympathetic axons do contain poly(A+) mRNA along their length in a pattern that changes gradually as axons elongate, from an evenly dispersed punctate distribution with strong growth cone staining to a distribution focused at branch points, varicosities, and some growth cones. Selective perturbations of the cytoskeleton revealed that the presence of axonal mRNA was dependent on microtubules (MTs), but not actin filaments, indicating that mRNA transport and/or anchoring within the axon are active processes involving MTs. Finally, reverse transcription-PCR amplification of RNAs from the axonal and somatic compartments showed that beta-actin mRNA was present in both compartments, whereas mRNA encoding alpha-tubulin was restricted to the somatic compartment and entirely absent from the axons. Thus, the mRNA populations in the soma versus the axon are both quantitatively and qualitatively different, and these neurons are able to direct specific mRNAs to the axon.

Animals↗
PubMed1997

Microtubule transport from the cell body into the axons of growing neurons.

The present studies test the hypothesis that microtubules (MTs) are transported from the cell body into the axons of growing neurons. Dissociated sympathetic neurons were cultured using conditions that allow us to control the initiation of axon outgrowth. Neurons were injected with biotin-labeled tubulin (Bt-tub) and then stimulated to extend axons. The newly formed axons were then examined using immunofluorescence procedures for MTs with or without Bt-tub. Because the Bt-tub is fully assembly competent, all MTs that assemble after injection will contain Bt-tub. However, MTs that exist in the neuron at the time of injection and persist during the subsequent incubation will not contain Bt-tub. Because the neurons were injected before extending axons, MTs without Bt-tub are initially localized to the cell body. We specifically determined whether these MTs appeared in the newly formed axon. Such a result can only be explained by the transport of these MTs from their initial location in the cell body into the axon. The newly formed axons of many neurons contained MTs both with and without Bt-tub. MTs without Bt-tub were detected all along the axon and in some neurons represented a substantial portion of the total polymer in the proximal and middle regions of the axon. These results show that MTs are transported from the cell body into growing axons and that this transport is robust, delivering MTs to all regions of the newly formed axon.

Animals↗
PubMed2026

Domain-specific mutations in unc-6/Netrin differentially affect dorsal-ventral axon pathfinding in Caenorhabditis elegans.

UNC-6/Netrin is a conserved regulator of dorsal-ventral axon and cell migrations. Here, we identified missense mutations in distinct UNC-6 domains and assessed their roles in dorsal VD/DD motor axon guidance and ventral anterior ventral microtubule (AVM) axon guidance. A missense mutation in a conserved residue of the laminin N-terminal (LN) domain (G289D) resulted in dorsal and ventral axon guidance defects similar to the unc-6 null. A distinct missense mutation in the LN domain (S120F) strongly perturbed ventral AVM axon guidance with minimal effects on dorsal VD/DD axon guidance. Mutations altering cysteine residues involved in disulfide bonding in the epidermal growth factor (EGF) domains were analyzed. EGF1(C321G) and EGF2(C347Y) caused both ventral and dorsal axon guidance defects, whereas EGF3(C410Y) specifically disrupted dorsal axon guidance. The crystal structure of UNC-6 shows conserved N-linked glycosylation at N114 and N128. These sites were not solely required for axon guidance, but mutations interacted genetically with unc-40 and unc-5 mutations, indicating that these residues have a role in UNC-6 signaling. Our results reveal the effects of UNC-6 domains on dorsal-ventral axon guidance and will inform studies on how these distinct UNC-6 domains interact with guidance receptors (e.g. UNC-40/DCC and UNC-5) and other extracellular molecules to mediate dorsal-ventral axon guidance.

Animals↗
PubMed1999

Axonal regeneration in the central nervous system of aplysia californica determined by anterograde transport of biocytin.

Rhythmic biting, a component of consummatory feeding behavior in the sea hare Aplysia californica, is eliminated following bilateral cerebral-buccal connective (CBC) crushes and recovers within 14 days postlesion. To assess axonal regeneration after CBC lesions, we used biocytin backfills of CBCs followed by fluorescence labeling with streptavidin-lissamine rhodamine. Anterograde transport of biocytin showed up to 1 mm of outgrowth by regenerating axons at 3 days postlesion. At 7 days postlesion, the regenerated axons approached or had entered the ipsilateral buccal neuropil and exhibited numerous varicosities; the average rate of axonal growth was 326 microm/day for the longest, most rapidly growing axons labeled in the CBC. The number of varicosities on labeled axons, suggestive of intercellular interactions, was increased dramatically at all times postlesion. At 14 and 20 days postlesion, regenerated axons branched extensively in the ipsilateral buccal neuropil, entered the contralateral buccal neuropil, and entered peripheral nerves on both sides of the midline. At these later times postlesion, some labeled axons encircled unlabeled buccal cell bodies and exhibited branches containing numerous varicosities, indicative of axosomatic contacts. Some regenerating axons were observed in the sheath of the CBC, but the vast majority of labeled axons remained confined to the connective core, as in control preparations. The bilateral projections within the buccal ganglia of labeled cerebral-to-buccal axons and the large number of varicosities present on these processes are indicative of regenerating axons and synapses that likely contribute to the functional recovery of rhythmic biting.

Animals↗
PubMed2002

Characterization of the optic nerve and retinal ganglion cell layer in the dysmyelinated adult Long Evans Shaker rat: evidence for axonal sprouting.

Myelin in the central nervous system (CNS) is hypothesized to help guide the growth of developing axons by inhibiting sprouting of aberrant neurites. Previous studies using animal models lacking CNS myelin have reported that increasing capacity for sprouting axons is negatively correlated with the degree of myelination. In the present study, we investigated the optic nerves of the recently identified Long Evans Shaker (LES) rat with prolonged dysmyelination of adult axons to determine whether the lack of myelin basic protein (MBP) in adult LES rats could manifest as increases in the population of CNS axons. We observed numerous small, unmyelinated axon profiles (<0.3 microm in diameter) clustered in bundles alongside normal caliber axons in dysmyelinated LES rats but not in normal myelinated Long Evans (LE) rats. These putative axon profiles resembled sprouting axons previously described in the CNS. Moreover, the high number of small putative axon profiles could not be accounted for by any significant increases in the number of ganglion cells and displaced amacrine cells in the ganglion cell layer when compared with normal rats as evaluated by using a variety of techniques. This finding suggests that the observed clusters of putative axon profiles were not due to developmental abnormalities in the retina but to the lack of myelin in the optic nerves of LES rats. The adult LES rat, therefore, may serve as a useful model to study the role of myelin in regulating axon development or axon regeneration after CNS injury in the adult mammalian system.

Animals↗
PubMed1985

Projection patterns of individual X- and Y-cell axons from the lateral geniculate nucleus to cortical area 17 in the cat.

Horseradish peroxidase was injected intracellularly into single, physiologically-identified X- and Y-cell geniculocortical axons projecting to area 17 of the cat. This injection anterogradely labeled the axon terminal fields in cortex and retrogradely labeled the somata of these same axons in laminae A and A1 of the lateral geniculate nucleus (LGN). The laminar projections of 21 X- and 15 Y-cell axons were analyzed. For these, the laminar terminations of ten X- and seven Y-cell axons were also related to their cells' positions in the A-laminae. The terminal fields of X- and Y-cell axons overlapped substantially in layers IV and VI of area 17. Some X-cells terminated mainly in IVb, others mainly in IVa, and still others throughout IVa and IVb. The latter two groups also projected up to 100 micron into lower layer III. Y-cells terminated primarily in layer IVa and projected up to 200 microns into lower layer III. Some also arborized throughout the depth of layer IVb. Both X- and Y-cell axons terminated throughout the depth of layer VI, although more so in the upper half. We found no relationship between the diameter of the parent axon and its sublaminar projection within layer IV. Within layer IV, X-cell axons generally terminated within a single, continuous clump and had surface areas of 0.6 to 0.9 mm2. Axons of Y-cells often terminated in two to three separate clumps, separated by terminal free gaps 400 to 600 micron wide. Their total surface areas, including gaps, were 1.0 to 1.8 mm2, roughly 1.6 times the surface areas of X-cell axons. Despite considerable overlap, Y-cell arbors contained significantly more boutons than did X-cell arbors. The sublaminar projections of the X- and Y-cell axons within layer IV reflected the locations of the cells' somata within the depth of the A-laminae. X-cells located in the dorsal or ventral thirds of the depths of the laminae projected mainly to layer IVa or throughout layer IV in cortex. Those located in the central thirds projected mainly to layer IVb. Y-cells showed a similar positional relationship, but they appeared to follow different rules. Y-cells in the outer thirds of the A-laminae projected mainly to layer IVa; those in the central thirds, in addition, expanded their projections to include layer IVb. In general, larger sized somata in the LGN gave rise to more widely spreading terminal arbors and greater numbers of boutons in cortex than did smaller somata.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Axonal degeneration and progressive neurologic disability in multiple sclerosis.

Accumulating data support axonal degeneration as the major determinant of irreversible neurological disability in patients with multiple sclerosis (MS). The extent of axonal injury correlates with the degree of inflammation in active MS lesions and occurs at early stages of disease, indicating that inflammatory demyelination is an important factor behind axon pathology at the relapsing-remitting stage of MS. Axonal loss from disease onset can remain clinically silent for many years, and permanent neurological disability develops when a threshold of axonal loss is reached and the CNS compensatory resources are exhausted. Lack of myelin-derived trophic support due to long term demyelination may cause continuous axonal degeneration in chronic inactive lesions at the secondary-progressive stage of MS. Axonal pathology is not limited to demyelinated lesions, but also extends into normal appearing white matter. The concept of MS as a neurodegenerative disorder has important clinical implications: First, proactive anti-inflammatory and immunomodulatory treatment should prevent or delay chronic disability since inflammation influences axonal injury. Second, the pathophysiological mechanisms underlying axonal degeneration in MS need to be clarified in order to develop novel neuroprotective therapeutics. Finally, surrogate markers of axonal pathology, such as N-acetyl aspartate, can be used to monitor axonal dysfunction, axonal loss and treatment efficiency in patients with MS.

Animals↗
PubMed2004

Progressive idiopathic axonal neuropathy--a comparative clinical and histopathological study with vasculitic neuropathy.

Patients with a progressive disabling idiopathic axonal neuropathy could have a potentially treatable immune mediated neuropathy. To evaluate whether progressive idiopathic axonal neuropathy could be a pathologically difficult to prove vasculitic neuropathy pathologically difficult to prove or if it could be a separate clinical entity (i. e. with the axon as the primary immunological target), we performed a comparative clinical and histopathological study in 10 patients with progressive idiopathic axonal neuropathy, 10 patients with vasculitic neuropathy, and 12 patients with chronic idiopathic axonal polyneuropathy (CIAP). The clinical features and disease course in patients with progressive idiopathic axonal neuropathy and patients with vasculitic neuropathy were similar. Six patients with progressive idiopathic axonal neuropathy had been treated with prednisone and/or intravenous immunoglobulin. Disability decreased in all these six patients, but also in two of the four non-treated patients. Upon reviewing the sural nerve biopsy specimens, vasculitis was found in one patient with progressive idiopathic axonal neuropathy. Vasculitis-associated signs of ischemic injury or inflammation (most notably: large variation in fascicular axonal degeneration, perivascular inflammation, inflammation of the blood vessel wall without lumen obstruction) were found in four patients with progressive idiopathic axonal neuropathy, in all patients with vasculitic neuropathy, but were absent in patients with CIAP. The findings show that there is a small chance of finding sural nerve vasculitis upon scrutinising biopsy examination in progressive idiopathic axonal neuropathy. The presence of vasculitis-associated signs in progressive idiopathic axonal neuropathy suggests that some of these patients could have vasculitic neuropathy, even if vasculitic lesions cannot be demonstrated. However, if inflammatory changes cannot be demonstrated this does not preclude an immune-mediated origin.

Adolescent↗
PubMed1988

Heterogeneous distribution of GABA-immunoreactive nerve fibers and axon terminals in the superior cervical ganglion of adult rat.

The distribution of axons and axon varicosities containing GABA was studied in the superior cervical ganglion of rat by light and electron microscopic immunohistochemistry. Two different polyclonal antibodies were used, which had been made against GABA conjugated by glutardialdehyde to bovine serum albumin. GABA-like immunoreactivity occurred in many axons within the cervical sympathetic trunk and in axons and axon varicosities around the principal nerve cells in the superior cervical ganglion. GABA-positive axons were intermingled with non-stained axons, except for a small group of fibers in the trunk where the staining was absent. The rostral part of the ganglion and some scattered patches were more densely innervated by GABA-positive axons than the middle and caudal parts. Within dense areas, some of the large ganglion cells were abundantly surrounded by GABA-positive nerve fibers, while the vicinity of others was devoid of any immunoreactive axon terminals. None of the principal ganglion cells contained GABA-like immunoreactivity, although a class of small cells scattered within the ganglion was stained. Transection of the cervical sympathetic trunk for 11 days caused the disappearance of GABA-like positivity from most of the fibers, and only very little GABA-like staining was revealed in some small cells, which resembled satellite cells. Ultrastructurally, the GABA-positive nerve fibers were unmyelinated. However, their terminal branches and varicosities accumulated around the perikarya and dendrites of certain principal ganglion cells were partly wrapped in glial processes. The present results provide evidence that the superior cervical ganglion of adult rat receives a significant number of GABA-positive axons from the cervical sympathetic trunk and that these axons provide an innervation which is heterogeneously distributed within the superior cervical ganglion and on ganglionic cells. The source and function of the GABA-positive axons remain to be elucidated.

Animals↗