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PubMed1992

Trying to understand axonal regeneration in the CNS of fish.

In contrast to the situation in mammals and birds, neurons in the central nervous system (CNS) of fish--such as the retinal ganglion cells--are capable of regenerating their axons and restoring vision. Special properties of the glial cells and the neurons of the fish visual pathway appear to contribute to the success of axonal regeneration. The fish oligodendrocytes lack the axon growth inhibiting molecules that interfere with axonal extension in mammals. Instead, fish optic nerve oligodendrocytes support--at least in vitro--axonal elongation of fish as well as that of rat retinal axons. Moreover, the fish retinal ganglion cells re-express upon injury a set of growth-associated cell surface molecules and equip the regenerating axons throughout their path and up into their target, the tectum opticum with these molecules. This may indicate that the injured fish ganglion cells reactivate the cellular machinery necessary for axonal regrowth and pathfinding. Furthermore, the target itself provides positional marker molecules even in adult fish. These marker molecules are required to guide the regenerating axons back to their retinotopic home territory within the tectum.

Animals↗
PubMed1993

Regeneration from crayfish phasic and tonic motor axons in vitro.

An explant culture system is described that allows examination of axonal growth from the tonically and phasically active motoneurons of the abdominal nerve cord of the crayfish. In this preparation, growth occurs from the cut end of the axon while the remainder of the motoneuron is undisturbed. In vitro growth from the branches of the third roots, which contain the axons from the tonic and phasic motoneurons of abdominal ganglia one through four, was verified as axonal by retrograde labeling of axons and neuronal somata within the nerve cord. Growth from the axons of phasic and tonic cells was observed as early as 24 h after plating and continued for an additional 7-10 days. The morphology and growth rates of the motor terminals differed between the tonic and phasic axons. The phasic axons grew significantly faster and branched more often than did the tonic motor axons. These differences in growth may be related to differences in motoneuron size or, may result from differences in electrical activity. Tonic motoneurons show spontaneous impulse activity for up to 6 days in culture, whereas phasic motoneurons show no spontaneous impulse activity. In addition, the differences in growth may be related to the morphological differences in tonic and phasic motor terminals observed in situ.

Animals↗
PubMed1994

Involvement of protein kinase C in the axonal growth-promoting effect on spinal cord neurons by target-derived astrocytes.

Astroglial cells participate in a variety of developmental events during neuronal morphogenesis. We have shown that axonal, but not dendritic, outgrowth of spinal cord neurons can be promoted by a diffusible factor or factors secreted from target region-derived cerebellar astroglia in vitro in comparison with spinal astroglia. In the present study, we examined the involvement of protein kinase C (PKC) in the axon-promoting effect by astroglia. The inhibition of PKC by sphingosine or by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) at high concentration greatly reduced the mean axonal length of spinal neurons cultured in medium conditioned by cerebellar astroglia (SCn-CBg), while activation of PKC by TPA at low concentration, or by retinoic acid, was not additive to the glial effect. The activation of PKC by TPA or retinoic acid promoted axon growth of spinal neurons cultured in medium conditioned by spinal astroglia (SCn-SCg), which otherwise would not be as supportive for axon growth as cerebellar astroglia. Western blotting and PKC activity assays showed that there was a trend for increased PKC activity and protein levels (in particular, PKC beta) in SCn-CBg cultures, which correlated with enhanced axon growth. Inhibition of PKC by sphingosine appeared to decrease protein levels, especially PKC beta, which correlated with suppressed axon outgrowth. In SCn-SCg cultures, phorbol ester activation of PKC increased both activity and protein levels of both PKC alpha and PKC beta. This activation correlated with stimulated axonal outgrowth. These results suggest that the glial signaling that regulates specific axonal outgrowth by target astroglia is mediated in part by the PKC second messenger system.

Animals↗
PubMed2006

Choline acetyl transferase and neuropeptide immunoreactivities are colocalized in somata, but preferentially localized in distinct axon fibers and boutons of cat sympathetic preganglionic neurons.

Cholinergic sympathetic preganglionic neurons (SPN) coexpress the biosynthetic enzyme for acetylcholine, choline acetyl-transferase (ChAT), and neuropeptides such as enkephalin (ENK) in their cell bodies. However, it is not clear whether they also coexpress ChAT and neuropeptides in axon fibers and boutons. To explore coexpression of ChAT and neuropeptides in somata and axon processes of SPN, we investigated, using immunohistochemistry, retrograde labeling, confocal analysis, and tridimensional reconstruction, whether ChAT and the peptides neurotensin, methionine-ENK, somatostatin, calcitonin gene-related peptide, and vasoactive intestinal peptide colocalize in somata, axons fibers, and boutons of cat SPN. Practically, complete colocalization for these peptides and ChAT was observed in SPN somata. Conversely, in most instances we observed independent localization of immunoreactivity (IR) for ChAT and the peptides in axon fibers and boutons. The minor colocalization between ChAT- and peptide-IR in preganglionic fibers could correspond to a sequential axonal transport of ChAT and peptides, since we observed coexistence of these transmitters after blocking axonal transport. Contrary to Dale's principle, our results suggest that SPN can synthesize ChAT and peptides in their cell bodies and route them to distinct axon boutons or terminals in sympathetic ganglia. Presence of axon boutons containing either ChAT or neuropeptides lead us to suggest a new neurochemical pattern of cotransmission in sympathetic ganglia based on the concurrent release of transmitters and cotransmitters from distinct presynaptic boutons, rather than in the corelease of these mediators from the same axon process. The possibility that cellular segregation could be transient and depend on functional requirements is considered.

Animals↗
PubMed1993

The role of the tracheae and musculature during pathfinding of Drosophila embryonic sensory axons.

Developing sensory axons were studied in Drosophila embryos which carried a mutation in the trachealess and/or the twist gene. In these embryos, the tracheae and/or somatic muscles, which represent part of the substrate on which sensory axons normally grow, are absent. The results demonstrate that in each of these three mutant backgrounds, the majority of sensory nerves form normally. This indicates that neither the tracheae nor the somatic musculature is absolutely required for pathfinding of the embryonic sensory axons. On the other hand, the incidence of misrouted axons is significantly increased, most strongly in the trh, twi double mutant. Furthermore, axonal elongation is considerably slowed down, and sensory neurons which fail to send out an axon are frequent. We take our results to indicate that peripheral axons in the Drosophila embryo may be guided by multiple cues which, acting together, ensure the high fidelity of axonal pathways observed in normal development. The removal of one of these cues by itself does not necessarily lead to the total disability of axons to reach their target, although it enhances the frequency of error in pathfinding.

Animals↗
PubMed1993

Time course of dorsal root axon regeneration into transplants of fetal spinal cord: an electron microscopic study.

Intraspinal transplants of fetal CNS tissue permit or enhance the regeneration of cut central axons of adult dorsal root ganglion (DRG) neurons. Some of these regenerated axons establish synapses with transplant neurons. The aims of the present study were to determine when regenerated DRG axons begin to form synapses with transplanted embryonic spinal cord neurons and whether these synapses are permanent. We also examined the development of transplant neuropil in areas innervated by the regenerated axons. Whole pieces of Embryonic Day 14 spinal cord were introduced into hemisection cavities made at the level of the lumbar enlargement, and the cut L4 or L5 dorsal root was juxtaposed to the transplant. Regenerated DRG axons immunoreactive for calcitonin gene-related peptide (CGRP) were labeled by immunohistochemical methods and examined by electron microscopy from 1 week to 1 year after surgery. CGRP-immunoreactive axon terminals made synaptic contacts with dendrites and perikarya of transplant neurons by 1 week after axotomy. The morphology of the synapses was immature. Large growth cone-like structures were also present at 1 week but not at 2 weeks or later. At 2 weeks, regenerated unmyelinated axons formed terminals similar to those found in animals surviving for 48 weeks. Axoaxonic synapses in which the pre- and postsynaptic elements were immunolabeled for CGRP and regenerated CGRP-labeled myelinated axons were observed at 4 weeks and later. The area of distribution of CGRP staining increased until 12 weeks and the synaptic density of regenerated CGRP-labeled terminals increased for 24 weeks. The results indicate that the synaptic terminals of regenerated primary afferent axons are permanently retained within fetal spinal cord transplants. Transplants may therefore contribute to the permanent restoration of interrupted neural circuits.

Animals↗
PubMed1994

Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants.

The permissivity of adult olfactory bulb to the ingrowth of olfactory axons could be due to the unique properties of ensheathing glia. To test whether these glial cells could be used to promote axonal regeneration in a spontaneously nonregenerating system, we transplanted suspensions of pure ensheathing cells into a rhizotomized spinal cord segment. Ensheathing cells were purified away from other cell types by immunoaffinity, using anti-p75 nerve growth factor receptor. After laminectomy at the lower thoracic level, the spinal cord was exposed and one dorsal root (T10) was completely transected at the cord entry point. The root stump was microsurgically anastomosed to the cord and a suspension of ensheathing cells was transplanted in the spinal cord at the dorsal root entry zone. Three weeks after transplantation, numerous regenerating dorsal root axons were observed reentering the spinal cord. Ingrowth of dorsal root axons was observed using DiI and antibodies against calcitonin gene-related peptide and growth-associated protein. Primary sensory afferents invaded laminae 1, 2, and 3, grew through laminae 4 and 5, and reached the dorsal grey commissure and lamina 4 of the contralateral side. We did not observe regenerating axons within the ipsilateral ventral horn and dorsal column. Transplanted ensheathing cells reached the same laminae as axons. Neither ensheathing cells nor regenerating axons invaded those laminae they did not innervate under normal circumstances. In conclusion, the regeneration of injured dorsal root axons into the adult spinal cord was possible after ensheathing glia transplantation. The use of ensheathing cells as stimulators of axonal growth might be generalized to other central nervous system injuries.

Animals↗
PubMed1996

Prior collateral sprouting of sensory axons delays recovery of pain sensitivity after subsequent nerve crush.

Regeneration of motor axons is enhanced if they have sprouted prior to nerve injury. We examined whether sensory axon regeneration and recovery of pain response was affected by previous collateral sprouting. In the experimental group of rats, the right saphenous, tibial, and sural nerves were transected and ligated. The peroneal nerve was left to sprout into the adjacent denervated skin. Two months later, the axons of the peroneal nerve were crushed in the sciatic nerve. In the control group, the right sciatic nerve was crushed at the same time that the saphenous, tibial, and sural nerves were transected. Recovery of pain response in the foot was determined by the skin pinch test. Sensory axon elongation rate was measured by the nerve pinch test. The number of myelinated axons was determined in nerve cross sections stained by Azur blue. Recovery of pain sensitivity in the animals of the experimental group was delayed for 2-3 weeks in comparison to the control group. Moreover, the spatial pattern of pain response in the experimental group was irregular, displaying residual regions of insensitive skin which were not present in controls. The elongation rate of regenerating sensory axons in the experimental group was not decreased, and the number of myelinated axons in the peroneal nerves was even about 10% higher than in the control group. Therefore, we assume that the terminal arborization of the neurilemmal tubes pertaining to the former axon sprouts delayed regrowth of sensory axon terminals in the skin.

Animals↗
PubMed1999

Constitutive expression of GAP-43 correlates with rapid, but not slow regrowth of injured dorsal root axons in the adult rat.

It has been postulated that the neuronal growth-associated protein GAP-43 plays an essential role in axon elongation. Although termination of developmental axon growth is generally accompanied by a decline in expression of GAP-43, a subpopulation of dorsal root ganglion (DRG) neurons retains constitutive expression of GAP-43 throughout adulthood. Peripheral nerve regeneration occurring subsequent to injury of the peripheral axon branches of adult DRG neurons is accompanied by renewed elevation of GAP-43 expression. Lesions of DRG central axon branches in the dorsal roots are also followed by some regenerative growth, but little or no increase in GAP-43 expression above the constitutive level is observed. To determine whether dorsal root axon regeneration occurs only from neurons which constitutively express GAP-43, we have used retrograde fluorescent labeling to identify those DRG neurons which extend axons beyond a crush lesion of the dorsal root. Only GAP-43 immunoreactive neurons supported axon regrowth of 7 mm or greater within the first week. At later times, axon regrowth is seen to occur from neurons both with and without GAP-43 immunoreactivity. We conclude that regeneration of injured axons within the dorsal root is not absolutely dependent on the presence of GAP-43, but that expression of GAP-43 is correlated with a capacity for rapid growth.

Amidines↗
PubMed2000

Robust regeneration of CNS axons through a track depleted of CNS glia.

Transected CNS axons do not regenerate spontaneously but may do so if given an appropriate environment through which to grow. Since molecules associated with CNS macroglia are thought to be inhibitory to axon regeneration, we have tested the hypothesis that removing these cell types from an area of brain will leave an environment more permissive for axon regeneration. Adult rats received unilateral knife cuts of the nigrostriatal tract and ethidium bromide (EB) was used to create a lesion devoid of astrocytes, oligodendrocytes, intact myelin sheaths, and NG2 immunoreactive cells from the site of the knife cut to the ipsilateral striatum (a distance of 6 mm). The regenerative response and the EB lesion environment was examined with immunostaining and electron microscopy at different timepoints following surgery. We report that large numbers of dopaminergic nigral axons regenerated for over 4 mm through EB lesions. At 4 days postlesion dopaminergic sprouting was maximal and the axon growth front had reached the striatum, but there was no additional growth into the striatum after 7 days. Regenerating axons did not leave the EB lesion to form terminals in the striatum, there was no recovery of function, and the end of axon growth correlated with increasing glial immunoreactivity around the EB lesion. We conclude that the removal of CNS glia promotes robust axon regeneration but that this becomes limited by the reappearance of nonpermissive CNS glia. These results suggest, first, that control of the glial reaction is likely to be an important feature in brain repair and, second, that reports of axon regeneration must be interpreted with caution since extensive regeneration can occur simply as a result of a major glia-depleting lesion, rather than as the result of some other specific intervention.

Animals↗
PubMed2001

Age-dependent effects of secreted Semaphorins 3A, 3F, and 3E on developing hippocampal axons: in vitro effects and phenotype of Semaphorin 3A (-/-) mice.

We studied the role of Semaphorins in the formation of hippocampal connections at embryonic and early postnatal stages. We show that the embryonic entorhinal cortex has a repulsive effect on embryonic hippocampal axons that disappears gradually at postnatal stages. Such chemorepulsion is blocked by Neuropilin-1 and -2 blocking antibodies. However, at perinatal stages, the inner layers of the entorhinal cortex attract CA1 axons. At these stages, Sema3A and Sema3F bind commissural and entorhinal axons. Sema3A and Sema3F repel hippocampal axons at E14-P2, but not at E13. A similar spatiotemporal pattern of chemorepulsion is observed for Sema3A on entorhinal axons, in contrast to Sema3F, which repels these axons only at postnatal ages. Sema3E also repels hippocampal axons but exclusively at E14. We show that Sema3A and Sema3F can induce the collapse of hippocampal growth cones and that membrane-bound Sema3A and Sema3F can guide hippocampal axons in the stripe assay. In sema3A (-/-) mice, the entorhinohippocampal projection is largely normal although single axons innervate aberrantly the stratum radiatum and the hilus. Thus, the chemorepulsion evoked by Sema3A, Sema3E, and Sema3F is dynamically regulated in the developing hippocampal formation.

Age Factors↗
PubMed1995

Axonal atrophy is a specific component of 2,5-hexanedione peripheral neuropathy.

To assess the relevance of previously identified axonal atrophy to hexanedione neuropathy, the present study quantitated fiber size in peripheral nerve of rats intoxicated with 2,5-hexanedione (HD) by either oral ingestion (0.4% in drinking water) or ip injection (0.4 g/kg/day). Prior to the appearance of neurobehavioral deficits, rats exposed to oral HD (77 days) exhibited axonal atrophy in proximal sciatic nerve and giant axonal swellings in distal tibial nerve. As oral-treated rats progressed to moderate (86 days) and severe (103 days) hindlimb weakness, both nerve regions contained a mixed population of atrophied and swollen axons. Rats injected with HD ip were sampled at behavioral endpoints that matched those of oral HD-treated rats. In sciatic and tibial nerves from rats treated ip, reductions in the axon area were similar to oral exposure. However, ip treatment did not produce giant axonal swellings in either nerve. Thus, although both routes of administration caused equivalent behavioral neurotoxicity, the expression of axonal swellings was route-dependent. This suggests that the production of swellings depends upon the HD exposure pattern. In contrast, axonal atrophy was prevalent in both nerve regions sampled and developed in parallel with behavioral deficits. In addition, atrophy was expressed regardless of the intoxication route which indicates that atrophy can occur independent of axonal swellings. Together, these attributes suggest that atrophy is a specific component of HD neurotoxicity.

Administration, Oral↗
PubMed1999

Initiating mechanisms involved in the pathobiology of traumatically induced axonal injury and interventions targeted at blunting their progression.

To gain better insight into the initiating factors involved in traumatically induced axonal injury cats and rats were subjected to various forms of traumatic brain injury. Following injury at intervals ranging from 10 min. to 3 hours, the animals were sacrificed and prepared in accordance with multiple immunocytochemical strategies capable of detecting focal changes in the axolemma, the subaxolemmal spectrin network, the underlying cytoskeleton as well as any related abnormalities in axoplasmic transport. Through these approaches it was recognized that the most severe forms of injury resulted in focal abnormalities of axonal permeability which were observed together with calpain-mediated spectrin proteolysis in the subaxolemmal network. These events were associated with compaction of the underlying neurofilaments and some microtubular loss which occurred without any direct evidence of overt axoplasmic proteolysis with the exception of the most severely injured fibers. In addition to these severely injured axonal profiles, other injured axons did not manifest overt changes in axolemmal permeability or early calpain-mediated spectrin proteolysis but demonstrated dramatic neurofilament and microtubular misalignment and impaired axoplasmic transport. Lastly, other small caliber axons showed another form of intraaxonal change manifested in the local pooling of organelles in the nodal and paranodal regions, with the suggestion that some of these changes may be reversible. In relation to these axonal responses the efficacy of various therapeutic investigations were assessed. The use of calcium chelators showed a trend for protection in those axons manifesting altered axolemmal permeability. However, the use of early and delayed hypothermia demonstrated dramatic protection resulting in significant reduction in the number of damaged axonal profiles. These studies illustrate the diversity and complexity of those axonal responses evoked by traumatic brain injury, suggesting that multiple forms of therapy may be needed to blunt these multifaceted forms of progression.

Animals↗
PubMed1986

Pyramidal tract of the cat: axon size and morphology.

The purpose of this work was to determine the number and morphology of pyramidal tract (PT) axons in the cat, using electron microscopy, modern methods of fixation, and computer-assisted morphometric analysis. Sections taken at the level of the medullary pyramids in three animals were fixed and magnified up to 10,000 X to produce photomicrographs. Morphological data were entered into computer files for analysis by tracing axon perimeters on micrographs mounted on a digitizer tablet. The number of axons per PT averaged 415,000, of which 88% were myelinated and 12% were unmyelinated. 90% of the myelinated axons fell in the diameter range 0.5-4.5 microns. Axons larger than 9 microns diameter accounted for 1% of the total; the largest were 20-23 microns. Myelinated axon mean diameter was 1.98 microns; because of the skewed distribution, with many small axons and a few very large axons, median diameter was 1.60 micron. Size distribution was relatively uniform throughout the PT cross section, with all sizes represented in all regions. However, the more medial regions had a higher proportion of small fibers than the more lateral regions: mean medial diameter was 1.85 micron while mean lateral diameter was 2.09 microns. Myelin sheath thickness averaged 7.9% of fiber diameter for axons up to 11 microns, but was constant at 0.9 micron for larger fibers. Myelinated fibers were distorted from the circular shape in cross section, with a mean circularity index (or form factor) of 0.85, which implies that the fibers could swell about 15% without rupture of the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Divergent projections of physiologically characterized rat ventral cochlear nucleus neurons as shown by intra-axonal injection of horseradish peroxidase.

An attempt was made to correlate electrophysiological and morphological characteristics of rat ventral cochlear nucleus neurons. Their axonal course and their soma morphology were investigated using the intra-axonal horseradish peroxidase method. Prior to labeling, neurons were characterized by recording their response patterns to acoustic stimulation with pure tones. Three types of cells were found: Category I (37 neurons) exhibited "primarylike" responses and a spontaneous firing rate below 10 spikes/s. Category II (21 neurons) showed "on" responses and little spontaneous activity. Category III (9 neurons) had "primarylike" responses like neurons in category I. However, the spontaneous activity rate of these neurons was significantly higher (mean: 95 spikes/s). Among the response categories, the morphological characteristics differed in some prominent aspects. Within each category, however, the morphological properties were rather similar. All neurons in category I were globular/bushy cells located in the area of the entrance of the cochlear nerve. The axon of each cell coursed along the ventral acoustic stria and consistently innervated the lateral superior olive ipsilaterally, and the nucleus of the trapezoid body and the nucleus of the lateral lemniscus contralaterally. Some neurons also projected to periolivary nuclei ipsilaterally and contralaterally. Neurons in category II were located in the posteroventral cochlear nucleus and were presumably multipolar/stellate cells. Their axons coursed via the intermediate acoustic stria and innervated mainly contralateral periolivary regions as well as the contralateral nucleus of the lateral lemniscus. Ipsilaterally, the lateral superior olive and the superior periolivary nucleus were innervated by some of the category II neurons. Somata types of neurons in category III could not be identified morphologically, but somata were located in caudal parts of the posteroventral cochlear nucleus that correspond to the octopus cell area. Their axons coursed via the intermediate acoustic stria and innervated periolivary regions and the contralateral nucleus of the lateral lemniscus. Thus, their axonal distribution differed only slightly from neurons in category II. These data confirm and extend previous findings regarding the efferent connections of ventral cochlear neurons. They emphasize the complexity of the axonal projection patterns of single cochlear nucleus cells. Since two types of response patterns and three types of axonal projection patterns have been observed, there remains an ambiguous relation between response pattern and axonal projection site.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1990

Morphology and neurophysiology of focal axonal injury experimentally induced in the guinea pig optic nerve.

A new model of focal axonal injury was reproduced by rapid and controlled elongation (uniaxial stretch) of the guinea pig optic nerve. Light microscopy study of optic nerve specimens after horseradish peroxidase injection into the vitreous of the animal's eye showed that axonal lesions were identical to those seen in human and primate post-traumatic diffuse axonal injury (DAI). The lesions were characterized by the formation of terminal clubs in severed axons and focal axonal enlargements in those axons that were lesioned-in-continuity. Visual-evoked potentials upon flash stimulation were recorded before and after injury. Mean amplitude and mean latency of occipital peaks were significantly elongated in the acute post-traumatic phase. Electron microscopy examination showed that the main axonal changes observed in this model were cytoskeleton disorganization, accumulation of axoplasm membrane-bound bodies at the site of terminal balls and dilatations-in-continuity and detachment of the axolemma from the myelin sheath. Such axonal alterations were similar to those found in many other biological models of central and peripheral axonal injuries in which the lesion was produced by invasive methods. This model is unique since it reproduces the same mechanism of injury and the identical lesions that have been demonstrated in humans and primates with post-traumatic (DAI).

Animals↗
PubMed1981

Developmental study of axon formation in the horizontal neurons of the retina of the chick embryo.

Among the types of horizontal cells of the avian retina, one has been described that has an axon terminating in a typical structure. The present study analyses the histogenesis of this axon whose initial outgrowth occurs on day 14 of incubation (HH-40). The axon terminal is first detectable, towards day 15 of incubation (HH-41), in the form of a varicose thickening possessing short filopodia. The formation of the axon and the growth of the axon terminal is coincident with a retraction of the perikaryal process. The axon usually originates from one of the principal dendrites and in these stages shows short and fine filopodia throughout its length. From day 16 onwards (synaptic) spines may be distinguished, both in the dendritic field and on the axon terminal. The growth of the axon, in the phase when the axon terminal still has not formed, may exhibit deflections and deviations in its course, the possible cause and mechanism of which are discussed.

Animals↗
PubMed1994

Markers of axonal injury in post mortem human brain.

beta-Amyloid precursor protein (beta APP) can be detected immunocytochemically at sites of axonal injury in the brain, and has recently been found to be a useful marker for injured axons in patients who survived for only 3 h after head trauma. It is transported by fast axonal transport and is thought to accumulate in detectable levels where the cytoskeleton breaks down. If this theory is correct, other substances should accumulate here in the same way, so we have used antibodies to other neuronal proteins to compare their efficacy as markers of axonal injury. SNAP-25, chromogranin A and cathepsin D also marked injured axons at all survival times studied (2.5 h-2 weeks), although they were not as sensitive or specific as beta APP. Immunolabelling for the 68-kDa neurofilament subunit (NF68) was present in most uninjured axons, and allowed axonal swellings to be seen in some cases. Synaptophysin, GAP-43, ubiquitin or tau did not label any normal or injured axons in this study. We, therefore, suggest that beta APP should be the immunocytochemical marker of choice for the detection of injured axons. This study also showed that microwave antigen retrieval significantly enhances the immunoreactivity of SNAP-25, chromogranin A, synaptophysin, GAP-43, ubiquitin and tau, in addition to that of beta APP, in formalin-fixed, paraffin-embedded tissue, and reveals NF68 antigenicity where it was not previously detectable.

Adolescent↗