Transganglionic Degeneration Research Articles

Ganglionic changes associated with transganglionic degeneration of capsaicin-sensitive primary sensory afferents: A quantitative morphometric and immunohistochemical study

Ganglionic changes associated with transganglionic degeneration of capsaicin-sensitive primary sensory afferents: A quantitative morphometric and immunohistochemical study

Ultrastructure of degenerative changes following ricin application to feline dental pulps.

The ultrastructure of degenerative changes within the ipsilateral trigeminal ganglion, and partes caudalis and interpolaris of the spinal trigeminal nucleus in the cat is described following the application of the potent toxin ricin to the tooth pulps of unilateral maxillary and mandibular posterior teeth, including the cuspids. Survival times ranged from 6 to 10 days. Typical changes identified within the ipsilateral trigeminal ganglion included myelin fragmentation and 'compartmentalization' of the axoplasm of medium-sized myelinated axons, while small myelinated and unmyelinated axons underwent a more variable response ranging from electron-lucent to electron-dense changes. The affected cell body was characterized by the presence of swollen, electron-lucent mitochondria, a reduction of cytoplasmic ribosomes and a filamentous hyperplasia. Other changes often included an eccentric nucleus and satellite cell proliferation. Degenerative changes often occurred in isolated elements surrounded by normal profiles, suggesting specificity of ricin within the trigeminal ganglion. Changes within brainstem axons showed both an electron-dense and a lucent, fragmenting type of axonal alteration. Terminal changes ranged from electron-dense to lucent and also included filamentous hyperplasia and 'hyperglycogenesis'. The altered axonal knobs contained round synaptic vesicles that were presynaptic to dendritic profiles and postsynaptic to terminals containing flattened synaptic vesicles. The above brainstem alterations were identified specifically in the following areas: ventrolateral, medial and dorsomedial pars interpolaris; the ventrolateral and mid-dorsal to dorsomedial areas of the marginalis and outer substantia gelatinosa layers of pars caudalis; and in ventral pockets corresponding to lamina V of the medullary dorsal horn. Dense alterations within terminals containing flattened synaptic vesicles that are typically presynaptic to primary afferents in these areas were rare findings, but along with vacuolization of dendritic profiles suggest a trans-synaptic effect possibly due to the exocytosis of ricin. The results are discussed in relation to different reports of dental projections and with regards to patterns of transganglionic degeneration.

Transganglionic degeneration in vibrissae innervating primary sensory neurons of the rat: a light and electron microscopic study.

Previous studies have shown that transection of peripheral branches of primary sensory neurons leads to light microscopical degeneration argyrophilia and ultrastructural changes in the central termination areas of these neurons. This type of degeneration has been termed transganglionic degeneration (TGD). In the present experiments TGD has been studied specifically in neurons innervating the rat vibrissae at the light and electron microscopic levels. Light microscopically, small amounts of degeneration argyrophilia are observed in the magnocellular zone of the trigeminal subnucleus caudalis at 8-14 days survival. At longer survival times there are substantial amounts of degeneration in this area. At the ultrastructural level the first signs of TGD are observed at 6 days survival, when some terminals show a small increase in electron density, loss of synaptic vesicles, and mitochondrial disintegration. Terminals showing a more advanced increase in electron density become common at 8 days survival, but few of them are still left at 14 days survival. Neurofilamentous terminals appear in small numbers 8-14 days postoperatively. Various forms of degeneration in myelinated axons are observed from 8 days survival and are common also at 80 days survival. Electron-dense axons are rather unfrequent, but more or less disrupted myelin sheaths containing disintegrated axoplasmic remnants and empty areas are common as well as extremely expanded myelin sheaths. Glial cells containing axonal and myelin debris are seen from 8 days survival and become a more common finding at longer survivals. A most striking finding 8-10 days postoperatively is a complex relationship between glial cells and less darkened terminals, indicating phagocytosis before reaching an entirely darkened state. The findings clearly show that peripheral nerve transection leads to severe central alterations in a population of mechanoreceptor neurons innervating the vibrissae of the adult rat.

Cell loss in lumbar dorsal root ganglia and transganglionic degeneration after sciatic nerve resection in the rat

The effects of sciatic nerve resection on lumbar dorsal root ganglion cells and their central branches have been studied in the adult rat. A quantitative analysis of the lumbar dorsal root ganglia indicated a 15–30% cell loss on the operated side. Argyrophilia indicating transganglionic degeneration was observed in Fink-Heimer stained sections from the lumbar spinal cord and the brainstem. The areas of degeneration argyrophilia were mainly located in the medial part of the ipsilateral L2–L6 dorsal horn laminae I–IV, the tract of Lissauer, the dorsal funiculus and the gracile nucleus. A few degenerating fibers could also be observed in the ipsilateral dorsal horn laminae V and VI, and in the ipsilateral ventral horn as well as in the contralateral dorsal and the gracile nucleus. The results confirm and extend previous findings at other levels and in other species. This suggests that cell loss and transganglionic degeneration may be general phenomena affecting a substantial proportion of primary sensory neurons following peripheral nerve injury.

Ultrastructural changes in the dorsal motor nucleus of monkey following bilateral cervical vagotomy.

The neurons of the dorsal motor nucleus (DMN) of the monkey (Macaca fascicularis) were of two main types: small (13 X 8 micron) and medium-sized (20 X 13 micron). The latter, which were the predominant form, contained a pale oval nucleus surrounded by organelle-rich cytoplasm. Between one and three long principal dendrites per section profile arose from each of the somata. Both axosomatic and axodendritic synapses were seen on these cells although the latter were more common. No structural changes were noted in the DMN 1-3 days after bilateral cervical vagotomy. Some of the dendrites of the medium-sized axotomized vagal neurons appeared darkened 5-10 days after the operation. With longer surviving intervals, i.e. 21 and 28 days after operation, darkened dendrites were more commonly seen and the cytoplasmic density of these dendrites was dramatically enhanced. Their mitochondria were pale and some of them also showed vesiculation. Both normal and degenerating axon terminals were seen to form synaptic contacts with the darkened dendrites. The degenerating axon terminals were characterized by the clumping of their round agranular vesicles. Both darkened dendrites and degenerating axon terminals were phagocytosed by hypertrophied astrocytes and activated microglial cells. Blood elements infiltrating into the DMN were a possible source for some of the neural macrophages. It was concluded from the present study that the dendrites of the vagal neurons were the first structures to degenerate in axotomy and these were subsequently removed by glial elements. Degenerating axon terminals on the darkened dendrites could represent endings of the central processes of peripheral vagal ganglion cells that had undergone transganglionic degeneration after damage to their peripheral processes.

Sciatic nerve transection produces death of dorsal root ganglion cells and reversible loss of substance P in spinal cord

Sciatic nerve section has been shown to reduce substance P (SP) in the dorsal horn of the spinal cord, but the mechanism which underlies the reduction is not understood. Whether SP levels subsequently recover as they do after dorsal rhizotomy has also been unknown. To test the hypothesis that transganglionic degeneration of primary afferents contributes to the reduction of SP, we have studied the changes in SP which result from section of the cat sciatic nerve and determined the extent of dorsal root ganglion (DRG) cell death. Sciatic nerve section resulted in DRG cell death, but the amount was variable and not seen in all animals. Reduction in dorsal horn and DRG SP was seen in all animals, and in the spinal cord it was followed by recovery. These sequelae resemble the changes which follow dorsal rhizotomy. After sciatic nerve section, the reduction in dorsal horn SP is small than after rhizotomy, the recovery more complete, and both the reduction and the recovery proceed more slowly. Evidence is presented that similar mechanisms may contribute to depletion of intraspinal SP after sciatic nerve section and after dorsal rhizotomy. The mechanisms contributing to recovery of spinal cord SP after sciatic nerve section may resemble known mechanisms of recovery that occur when the lesion is central.

Ultrastructure of transganglionic degeneration in brain stem trigeminal nuclei during normal primary tooth exfoliation and permanent tooth eruption in the cat.

Electron microscopy is used to study changes in the axons and terminals in the cat brain stem trigeminal nuclei, main sensory, and partes interpolaris and caudalis, during the process of natural tooth shedding. Areas previously showing light optical argyrophilic degeneration products and adjacent areas lacking this degeneration are included. Various types of alteration occur early during tooth loss, including increased presumed glycogen, increased cytoplasmic density, flocculence, lucency, and neurofilamentous hyperplasia. By the stage of maximum exfoliation, terminals and axons of marked density become prominent in areas showing argyrophilia, whereas nondense forms occur elsewhere. By late eruption ages, all forms of degenerated terminals and axons are rare, but phagocytes are heavily laden with similar forms of debris. The sequence of ultrastructural events is discussed in light of recent studies of transganglionic degeneration, their correlation with light microscopic findings, and the potential implications for central plasticity in this system.

Retrograde and transganglionic degeneration of sensory neurons after a peripheral nerve lesion at birth

The sciatic nerve of newborn rats (≤16 h old) was crushed with a watchmaker forceps. During the first 4 weeks after the injury, examination of ipsilateral L4 through L6 dorsal root ganglia, their dorsal nerve roots, and the dorsal funiculus revealed the presence of degenerating myelin and axons. Chromatolysis was not observed. In the spinal cord, the degenerating argyrophilia was restricted to the medial part of the dorsal funiculus (fasciculus gracilis). This is interpreted as transganglionic degeneration of the central processes of the pseudounipolar cells. Twelve weeks after nerve crush, there was a noticeable reduction in the size of the leg, foot, and muscles innervated by the sciatic nerve as well as a substantial loss ( P < 0.001) of neurons and myelinated axons in ipsilateral spinal ganglia and their dorsal nerve roots. The reduction was most prominent among the larger sensory neurons (>40 μm) and the larger myelinated axons. A total loss of about 60% of sensory neurons was found in the L4 through L6 spinal ganglia. About 58 and 64% of the myelinated axons were lost in L4 and L5 dorsal roots, respectively. The remaining perikarya and dorsal root axons were hypoplastic.

Intercostal nerve transection and its effect on the dorsal root ganglion. A quantitative study on thoracic ganglion cell numbers and sizes in the rat.

The effect of intercostal nerve transection on the number and size distribution of thoracic spinal ganglion cells has been investigated and correlated with transganglionic degeneration (TGD) in the spinal cord dorsal horn. Unilateral transections were made of 3 or 11 consecutive intercostal nerves. Twenty to 180 days later the animals were perfused and relevant ganglia from both sides embedded in resin, serially sectioned and stained. Counts of neuronal nucleoli were made and perikaryal areas of ganglion cells measured. The number of neurons was significantly reduced on the operated side 20 days postoperatively. The cell loss increased slightly to about 35% with longer survival times. Analysis of cell size spectra showed a bilaterally symmetrical picture in normal animals. No distortions of the cell size spectrum were observed at 20 to 70 days after nerve transections. Transganglionic degeneration was found in the dorsal horn from 20 to 70 days postoperative survival, but not at 180 days. The findings indicate that TGD in the dorsal horn is related to a loss of ganglion cells in the corresponding spinal ganglion. There does not seem to be a preferential loss of any particular size class of cells.

Ultrastructural study of transganglionic degeneration following dental lesions.

Transganglionic degeneration in the trigeminal main sensory nucleus (MSN) and pars interpolaris (PI) was studied in cats following dental lesions. At early survival times, three types of terminal alteration were seen in both MSN and PI: (1) flocculent degeneration, (2) neurofilamentous hyperplasia and, (3) glycogen accumulation. With longer survival times, the magnitude of these terminal alterations increases. Electron dense degeneration was only seen in the ventral half of PI. Phagocytosis of the altered terminals was also observed. The study suggests a plausible explanation for the variations observed in the CNS projection of primary afferents with degeneration and with HRP transport studies.

Somatotopic organization of the thoracic spinal nerve in the dorsal horn demonstrated with transganglionic degeneration.

Transganglionic degeneration in primary sensory neurons (TGD) has been studied with the Fink-Heimer and cupric silver methods in the adult rat after transection of thoracic spinal nerve branches. Degeneration was found in the ipsilateral dorsal horn after 13 to 53 days postoperative survival. It was observed in laminae III and IV, inconsistently in lamina I, but not in lamina II (substantia gelatinosa). After transection of the dorsal ramus of the spinal nerve degeneration was seen in the lateral third of the laminae. Transection of the intercostal nerve (ventral ramus) at about the costal angle gave rise to degeneration in the medial two-thirds and transection more distally, at about the mid-clavicular line, in the most medial part of the dorsal horn. The results are in accordance with previous anatomical and physiological studies of the somatotopical organization of the dorsal horn. They clearly show the usefulness of TGD as a tool for analysis of central projections of primary sensory neurons.

Further observations on transganglionic degeneration in trigeminal primary sensory neurons

Transganglionic degeneration has been studied with the Fink-Heimer method in the trigeminal sensory nuclei of adult cats and rats following peripheral nerve transections. Degeneration was observed ipsilaterally as well as contralaterally in all cats, surviving 11–30 days after transection of the infraorbital nerve. In the rats the infraorbital or the auriculotemporal nerve was transected. After transection of the former nerve the first signs of transganglionic degeneration were observed after 7 days postoperative survival and even after 130 days there were still a lot of degenerating structures present. Between 7 and 14 days survival there was a small amount of degeneration in substantia gelatinosa. After transection of the auriculotemporal nerve, degeneration was observed only in the most caudal parts of the trigeminal sensory nuclear complex. Opposite to the situation in the cat, there was no contralateral degeneration in the rat. All degeneration areas were somatotopically organized, both in the cat and in the rat. The results are discussed in relation to a previous study of transganglionic degeneration in the trigeminal sensory nuclear complex by the authors and to anatomical and physiological studies of somatotopic organization in the trigeminal sensory nuclei. They clearky show the value of transganglionic degeneration used as a tool for analysis of central projections of primary sensory neurons.

An ultrastructural study of transganglionic degeneration in the main sensory trigeminal nucleus of the rat

In adult rats subjected to unilateral transection of the infraorbital nerve, the main sensory trigeminal nucleus was studied by electron microscopy. Post-operative survival times varied between 2 and 60 days. A variety of ultrastructural alterations was observed from the sixth post-operative day onwards. These changes were in many respects similar to those seen in the course of Wallerian degeneration. Neurofilamentous boutons and axons were found 6-30 days post-operatively. Various types of dark boutons were observed between 7 and 30 days and axonal changes indicative of degeneration between 7 and 60 days post-operatively. Astrocytes and microglial cells contained degenerating structures 7-60 days post-operatively. The alterations observed in the present study are interpreted as related, at least in part, to the nerve cell degeneration and the nerve cell death previously shown to occur in the trigeminal ganglion after infraorbital nerve transection.

Electron microscopy of degenerating axons and terminals in spinal trigeminal nucleus after tooth pulp extirpations.

Following multiple tooth pulp extirpations, electron microscopic preparations show degenerating axons and synaptic terminals in the same region of the brain stem trigeminal nucleus previously demonstrating degeneration by light-optical methods. The observations confirm the phenomenon of transganglionic degeneration in this system and identify the class of central nervous system axons and synapses specifically related to innervation of the teeth.

Transganglionic degeneration in the spinal trigeminal nucleus following removal of tooth pulps in adult cats

It is generally thought that transganglionic degeneration of central axons following lesions of their peripheral processes does not occur in adult nervous systemS, 6. For this reason there has been a lack of anatomical descriptions of the central distribution of specific groups of peripheral sensory axons. We, however, have found reproducible axonal and terminal degeneration in specific regions of the spinal trigeminal nucleus in adult cats following tooth pulpectomies 12. Healthy adult cats were used and the absence of dental pathology was confirmed prior to operation and in the controls. Under pentobarbital anesthesia and using appropriate aseptic dental procedures, the pulps were completely removed from all of the teeth on one side of 12 animals. Following postoperative survival times of 7, 9, 11, 14, 21, 28 and 100 days the animals were perfused with 4~o formaldehyde in a phosphate buffer 11. Transverse frozen sections through the brain stem, including the major parts of the spinal trigeminal nucleus, were stained by either the NautaGygax v or the Fink-Heimer (I) 4 technique. Two normal, unoperated animals were sacrificed and processed in the same fashion to serve as controls. Fig. 1 illustrates the pattern of degeneration observed at 1 l days. Unequivocal axonal and terminal degeneration (Fig. 2) is seen predominantly in the ventral half to one-third of the subnucleus interpolaris of the spinal trigeminal complex, near and immediately rostral to the obex, with very much less in the adjacent subnuclei (caudalis and oralis). The distribution is bilateral, but heaviest on the side of the lesion. The occurrence of contralateral degeneration is surprising in view of what is known of the organization of this system 2, but it is a consistent finding here. A crossing pathway of degenerating fibers cannot be identified with certainty. The amount of degeneration is less at shorter or longer survivals, but the pattern is similar in each. Control animals, with healthy teeth, show no degeneration.

FUNCTIONAL ORGANIZATION OF TACTILE CUTANEOUS AFFERENTS WITHIN THE SEMILUNAR GANGLION AND TRIGEMINAL SPINAL TRACT OF THE CAT.

ArticlesFUNCTIONAL ORGANIZATION OF TACTILE CUTANEOUS AFFERENTS WITHIN THE SEMILUNAR GANGLION AND TRIGEMINAL SPINAL TRACT OF THE CATI. Darian-Smith, Patricia Mutton, and Robyn ProctorI. Darian-Smith, Patricia Mutton, and Robyn ProctorPublished Online:01 Jul 1965https://doi.org/10.1152/jn.1965.28.4.682MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByCurrent understanding of trigeminal ganglion structure and function in headache10 July 2018 | Cephalalgia, Vol. 39, No. 13Stable synchronized high-frequency signals from the main sensory and spinal nuclei of the pig activated by Aβ fibers of the maxillary nerve innervating the snoutBrain Research, Vol. 959, No. 1Musculotopic organization in the motor trigeminal nucleus of the reeler mutant mouseBrain Research, Vol. 666, No. 1Histamine actions and comparison with substance P effects in trigeminal neuronsNeuroscience, Vol. 55, No. 2Responses of cat C1 spinal cord dorsal and ventral horn neurons to noxious and non-noxious stimulation of the head and faceBrain Research, Vol. 555, No. 2Cervical Spinal Cord Neurons Receiving Sensory Input from the Cranial Vasculature7 November 2016 | Cephalalgia, Vol. 11, No. 2Topographic study of the feline trigeminal ganglion via the horseradish peroxidase tracer methodBrain Research, Vol. 476, No. 2Somatotopic organization of tooth pulp primary afferent neurons in the catBrain Research, Vol. 477, No. 1-2Electrophysiological responses of trigeminal root ganglion neurons in vitroNeuroscience, Vol. 24, No. 2Somatotopic Organization and Transmedian Pathways of the Rat Trigeminal Ganglion8 November 2016 | Journal of Dental Research, Vol. 63, No. 11Accessory innervation of mandibular anterior teeth in cats: a horseradish peroxidase studyBrain Research, Vol. 298, No. 2A horseradish peroxidase study of feline mandibular incisorsBrain Research, Vol. 260, No. 2The sensory representation of the dura mater in the trigeminal ganglion of the catNeuroscience Letters, Vol. 31, No. 3Peripheral and central substrates involved in the Rostrad transmission of nociceptive informationPain, Vol. 13, No. 1Peripheral and central pathways in painPharmacology & Therapeutics, Vol. 14, No. 3Histochemical evidence for strictly ipsilateral innervation of maxillary canine teeth in catsExperimental Neurology, Vol. 70, No. 1Motor and sensory centers for the innervation of mandibular and sublingual salivary glands: A horseradish peroxidase study in the dogBrain Research, Vol. 189, No. 2A lack of peripheral transmedian innervation of feline mandibular canine teeth as determined by horseradish peroxidaseBrain Research, Vol. 179, No. 2Further observations on transganglionic degeneration in trigeminal primary sensory neuronsBrain Research, Vol. 162, No. 1Topography of cutaneous spinal ganglion cells in the frog(Rana esculenta)Brain Research, Vol. 156, No. 1Ectopic action potential generation in peripheral trigeminal axonsExperimental Neurology, Vol. 62, No. 2Location of feline trigeminal ganglion cells innervating maxillary canine teeth: A horseradish peroxidase analysisExperimental Neurology, Vol. 57, No. 1Afferent excitability compared using pulsating versus constant direct current electroanalgesia in cat tooth pulpExperimental Neurology, Vol. 53, No. 2Location of cat trigeminal ganglion cells innervating dental pulp of upper and lower canines studied by retrograde transport of horseradish peroxidaseBrain Research, Vol. 99, No. 1The selective vulnerability of evoked potentials in the trigeminal sensory root to graded thermocoagulationExperimental Neurology, Vol. 49, No. 1Trigeminal influences on extensor muscles of the neckExperimental Neurology, Vol. 47, No. 2Transmedian innervation of canine tooth pulp in catsExperimental Neurology, Vol. 44, No. 1Excitability changes at the intramedullary terminals of lingual mechanoreceptor afferents induced by volleys in the cat's lingual nerveBrain Research, Vol. 57, No. 1Somatotopic organization of the trigeminal ganglion in the ratArchives of Oral Biology, Vol. 18, No. 4Respones of trigeminal ganglion and brain stem neurones in the cat to mechanical and thermal stimulation of the faceBrain Research, Vol. 42, No. 2A histological study of chromatolytic cell groups in the trigeminal ganglion of the ratArchives of Oral Biology, Vol. 17, No. 3Extraocular muscle proprioception and the descending trigeminal nucleusExperimental Neurology, Vol. 33, No. 1Tactile direction sensitivity of area 2 oral neurons in the rhesus monkey cortexBrain Research, Vol. 27, No. 2Location of the neurons innervating tendon spindles of masticator musclesExperimental Neurology, Vol. 25, No. 4Coding of somatic sensory input by vibrissae neurons in the rat's trigeminal ganglionBrain Research, Vol. 12, No. 1Peripheral pathway of eye muscle proprioceptionExperimental Neurology, Vol. 22, No. 1Interaction of peripheral and central input in the main sensory trigeminal nucleus of the catExperimental Neurology, Vol. 17, No. 2Eye muscle proprioception and the semilunar ganglionExperimental Neurology, Vol. 16, No. 2 More from this issue > Volume 28Issue 4July 1965Pages 682-694 https://doi.org/10.1152/jn.1965.28.4.682PubMed14347628History Published online 1 July 1965 Published in print 1 July 1965 Metrics

Four aspects of trigeminal nucleus and a paradox.

Four aspects of trigeminal nucleus and a paradox.