Biomedical subjects

K Fried

Publications and source records attributed to K Fried.

At least 19 recordsLinked to original sources

PubMed2006

Expression of HMGB1 during tooth development.

High mobility group box 1 (HMGB1) is a nuclear and cytosolic protein that can act as a transcription factor, a growth factor, or a cytokine. To elucidate a possible role for HMGB1 in tooth development, we have studied the expression of HMGB1 and its receptor RAGE (receptor for advanced glycation end-products) during the late fetal and early postnatal period of rat by using light- and electron-microscopic immunohistochemistry. Low HMGB1 protein expression was observed during fetal and newborn stages of tooth development. However, from postnatal day 5 (P5) onward, a marked increase occurred in the levels of the protein in most dental cell types. Expression was particularly high in ameloblasts and odontoblasts at regions of ongoing mineralization. Although most HMGB1 immunoreactivity was confined to cell nuclei, it was also present in odontoblast cytoplasm. At P5, ameloblasts and odontoblasts also showed RAGE immunoreactivity, and reverse transcription-polymerase chain reaction demonstrated both HMGB1 and RAGE mRNA in human dental pulp cells in vitro. Immunoblots performed on extracts from bovine dentin demonstrated a principal band at approximately 27 kDa, indicating that HMGB1 participates in tooth mineralization. The expression of both ligand and receptor suggests an autocrine/paracrine HMGB1 signalling axis in odontoblasts.

Adult↗

PubMed2004

Neurites from trigeminal ganglion explants grown in vitro are repelled or attracted by tooth-related tissues depending on developmental stage.

Although neurite attracting factors are present in the developing dental pulp and trigeminal ganglion (TG) axons can respond to such factors, nerve fibres do not enter the tooth pulp until a late developmental stage compared with surrounding tissues supplied by the TG. This suggests that the dental pulp secretes neurite growth inhibitory molecules. Semaphorins represent one group of substances, which can inhibit/repel growing neurites. The aims of the present study were to investigate if dental tissue explants inhibit/repel neurite growth from TGs at some developmental stages in vitro, and if so, to seek evidence for or against a participation of semaphorins in that interaction. By co-culturing mandibular or dental epithelial and mesenchymal tissue explants and TGs in collagen gels, we found that embryonic day 11 (E11) mandibular and E13 dental mesenchymal explants repel neurites from corresponding TGs. Repulsion was replaced by attraction if tissues from late embryonic or early postnatal mice (E17-postnatal day 5) were used. Using semi-quantitative reverse transcription/polymerase chain reaction we showed that a number of semaphorins were expressed by tooth-related mesenchyme collected from embryonic and postnatal mice. The expression of some semaphorins (3A, 3C, 3F, 4F, 5B, 6A, 6B and 6C) was high early in development and then decreased in a temporal pattern that correlated with neurite inhibitory/repulsive effects of dental mesenchyme observed in co-cultures. The expression of other semaphorins increased with development (3B, 4A and 7A), whilst others varied irregularly or remained at a fairly constant level (3E, 4B, 4C, 4D, 4G and 5A). Immunohistochemistry was used to determine if tooth-related nerve fibres possess neuropilins. This revealed that axons surrounding embryonic tooth buds express neuropilin-1, but not neuropilin-2. In postnatal teeth, nerve fibres located within the tooth pulp were immunonegative for neuropilin-1 and neuropilin-2. We conclude that developing mandibular/dental mesenchyme can inhibit/repel neurite growth in vitro. Our results support the hypothesis that semaphorins may be involved in this interaction.

Animals↗

PubMed2003

Responses of rat trigeminal neurones to dental pulp cells or fibroblasts overexpressing neurotrophic factors in vitro.

The adult dental pulp is innervated by sensory trigeminal axons and efferent sympathetic axons. Rat trigeminal ganglia extend neurites when co-cultivated in vitro with pulpal tissue explants, suggesting that pulpal cells secrete soluble molecules that stimulate the growth of trigeminal ganglion axons. In addition, cultured pulpal cells produce mRNAs for neurotrophins and glial cell line-derived neurotrophic factor-family members. These data suggest that neurotrophic factors are involved in the formation of a pulpal innervation. Here, we examine how pulpal cells and 3T3 fibroblasts overexpressing certain neurotrophic factors (nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, glial cell line-derived neurotrophic factor or neurturin) influence survival and growth of single trigeminal ganglion neurones in vitro in quantitative terms. The results show that most of the neurotrophic factor-overexpressing fibroblasts induce similar neuronal soma diameters, but higher survival rates and neurite lengths compared with pulpal cells. With respect to neurite growth pattern, trigeminal ganglion neurones co-cultured with fibroblasts overexpressing nerve growth factor develop a geometry that is most similar to that seen in co-cultures with pulpal cells. We conclude that none of the fibroblasts overexpressing neurotrophic factors can fully mimic the effects of pulpal cells on trigeminal ganglion neurones, and that nerve growth factor promotes a neurite growth pattern most similar to the picture seen in co-cultures with pulpal cells.

3T3 Cells↗

PubMed2002

Expression of ErbB3, ErbB4, and neuregulin-1 mRNA during tooth development.

The receptor tyrosine kinases ErbB3 and ErbB4, which bind to various variants of neuregulin (NRG), play fundamental roles in neural development and in organs, which form through epithelial-mesenchymal interactions. Here, we demonstrate that NRG-1 and the receptors ErbB3 and ErbB4 are expressed locally during rodent tooth development. However, the mRNA expression patterns of ErbB3 and ErbB4 were distinctly different during odontogenesis. Examinations of teeth in genetically heart-rescued ErbB4-/- mice did not reveal any obvious deviation from the normal phenotype. The results suggest that ErbB3 and ErbB4 may participate in tooth morphogenesis. The specific interactions between NRG isoforms and ErbB receptors during this process remain to be determined.

Animals↗

PubMed2001

Rat tooth pulp cells elicit neurite growth from trigeminal neurones and express mRNAs for neurotrophic factors in vitro.

Molecular factors control the developmental ingrowth of axons to the tooth pulp. Here we examine the ability of pulpal cells to induce neurite outgrowth from neonatal rat trigeminal neurones (TGNs) in vitro. We found that TGNs emitted neurites and formed networks of branches in relation to pulpal cells. Neurones co-cultured with a mixture of pulpal cells and 3T3 fibroblasts formed networks exclusively in relation to the pulpal cells. Cultivated pulpal cells and pulpal tissue produced mRNAs for all neurotrophins and members of the glial cell line-derived neurotrophic factor family. Hence, rat pulpal cells have neuritogenic effects on single TGNs in vitro, that may be associated with secretion of neurotrophic factors.

3T3 Cells↗

PubMed2001

Phase I and pharmacokinetic study of two sequences of gemcitabine and docetaxel administered weekly to patients with advanced cancer.

PURPOSE: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and effect of drug sequence on toxicities and pharmacokinetics of the combination of gemcitabine and docetaxel. METHODS: A total of 34 patients with advanced cancers were treated with gemcitabine and docetaxel on days 1 and 8 of each 21-day cycle according to the following dose escalation schedule: level 1, 800 and 30 mg/m2, respectively; level 2, 800 and 40 mg/m2; level 3, 1,000 and 40 mg/m2; and level 4, 1,250 and 40 mg/m2. At each dose level, at least three patients were assigned to one of the two sequences of drug administration: gemcitabine-->docetaxel or docetaxel-->gemcitabine. Once the MTD had been reached, six additional patients, who had received no more than one chemotherapy regimen, were enrolled to dose levels 3 and 4 (gemcitabine-->docetaxel) to determine the MTD in minimally pretreated patients. RESULTS: Neutropenia was the most frequent DLT with an overall incidence of 23.5%. Grade 3/4 neutropenia occurred in 62% of patients (8/13) who had received two or more prior chemotherapy regimens, but not at all (0/15) in patients who had received no more than one prior chemotherapy regimens (P< 0.001). Additional DLTs included grade 4 diarrhea and grade 4 stomatitis in one patient each. The MTD was determined to be gemcitabine 800 mg/m2 and docetaxel 40 mg/m2 in patients who had received two or more prior chemotherapy regimens. However, minimally pretreated patients (no more than one prior chemotherapy regimen) were able to tolerate higher doses with an MTD of gemcitabine 1,250 mg/m2 and docetaxel 40 mg/m2. There were no significant differences in toxicities or pharmacokinetics between the two sequences of administration. Partial and minor responses were observed in 23.5% of patients: non-small-cell lung (two of eight), gastric (two of three), head and neck (one of two), bladder (two of four) and hepatocellular cancer (one of one). CONCLUSIONS: The combination of gemcitabine and docetaxel administered on days 1 and 8 every 21 days was feasible and well tolerated in patients with advanced malignancies. The sequence of administration had no significant effect on the toxicity or pharmacokinetics of either drug. Minimally pretreated patients tolerated higher doses of this combination without significant toxicities. This schedule and combination demonstrated activity in a variety of solid tumors, and merits further evaluation.

Adult↗

PubMed2001

Nerve injury-induced pain in the trigeminal system.

This article reviews some recent findings on peripheral mechanisms related to the development of oro-facial pain after trigeminal nerve injury. Chronic injury-induced oro-facial pain is not in itself a life-threatening condition, but patients suffering from this disorder undoubtedly have a reduced quality of life. The vast majority of the work on pain mechanisms has been carried out in spinal nerve systems. Those studies have provided great insight into mechanisms of neuropathic spinal pain, and much of the data from them is obviously relevant to studies of trigeminal pain. However, it is now clear that the pathophysiology of the trigeminal nerve (a cranial nerve) is in many ways different to that found in spinal nerves. Whereas some of the changes seen in animal models of trigeminal nerve injury mimic those occurring after spinal nerve injury (e.g., the development of spontaneous activity from the damaged axons), others are different, such as the time-course of the spontaneous activity, some of the neuropeptide changes in the trigeminal ganglion, and the lack of sprouting of sympathetic terminals in the ganglion. Recent findings provide new insights that help our understanding of the etiology of chronic injury-induced oro-facial pain. Future investigations will hopefully explain how data gained from these studies relate to clinical pain experience in man and should enable the rapid development of new therapeutic regimes.

Animals↗

PubMed2001

Kinetics of monochloroacetic acid in adult male rats after intravenous injection of a subtoxic and a toxic dose.

Distribution, metabolism, and excretion of monochloroacetic acid (MCA) were examined in adult male rats at a subtoxic (10 mg/kg) and a toxic (75 mg/kg) dose. Rats were injected i.v. with [14C]MCA and housed individually. Urine and feces were collected. Animals were euthanized at different time intervals after dosing and tissues procured. Radioactivity in aliquots showed very rapid distribution of MCA to tissues. Concentrations of MCA in plasma, liver, heart, lungs, and brown fat paralleled each other, whereas those in brain and thymus did not. There was no dose proportionality in tissue concentrations. Elimination of MCA from plasma required modeling by two compartments. Most of the radioactivity found in plasma was parent MCA. Elimination rate constant (K(10)) and distribution rate constant (K(12)) were greatly reduced at the toxic dose. Elimination of the toxic dose was further retarded due to increased retention of MCA in the peripheral compartment as indicated by increased mean residence times in most tissues. A very large fraction of dose was found in the gastrointestinal tract, almost all of which was reabsorbed. Attempts to reduce toxicity by blocking the enterohepatic circulation with activated charcoal or cholestyramine failed. Radioactivity found in bile was associated with one metabolite more polar than the parent compound. A very large fraction of dose (73 and 59%) was found in urine, 55 to 68% of which was parent MCA. The rate-determining step in the toxicity of MCA was identified as its detoxification by the liver. A therapeutic approach in MCA intoxications is suggested.

Acetates↗

PubMed2000

Neuropeptide- and tyrosine hydroxylase-immunoreactive nerve fibers in painful Morton's neuromas.

We examined the expression of three neuropeptides that have been implicated in nociceptive transmission, and the sympathetic nerve fiber marker tyrosine hydroxylase, in 11 painful human Morton's neuromas, using immunohistochemistry. Antibodies against the neural markers RT97 and PGP 9.5 were used to map the general nerve fiber organization of the neuromas. Four specimens of normal human peripheral nerves were used as controls. Substance P, calcitonin gene-related peptide, and neuropeptide Y immunoreactivities were more pronounced in neuroma tissue than in control nerves. Neuropeptide immunofluorescence was seen both in larger nerve fiber trunks and in masses of disorganized axon profiles dispersed in loose connective tissue. Tyrosine hydroxylase immunoreactivity was present at varying levels of expression in neuroma nerve fiber trunks, in connective tissue nerve fiber bundles, and around some blood vessels. Our findings suggest that neuropeptides are involved in the response to injury in Morton's neuromas and that they could play a role in initiation or modulation of pain. In addition, pain from Morton's neuromas could be influenced by sympathetic nerve fibers.

Adult↗

PubMed2000

Expression of sodium channel SNS/PN3 and ankyrin(G) mRNAs in the trigeminal ganglion after inferior alveolar nerve injury in the rat.

The inferior alveolar nerve is a sensory branch of the trigeminal nerve that is frequently damaged, and such nerve injuries can give rise to persistent paraesthesia and dysaesthesia. The mechanisms behind neuropathic pain following nerve injury is poorly understood. However, remodeling of voltage-gated sodium channels in the neuronal membrane has been proposed as one possible mechanism behind injury-induced ectopic hyperexcitability. The TTX-resistant sodium channel SNS/PN3 has been implicated in the development of neuropathic pain after spinal nerve injury. We here study the effect of chronic axotomy of the inferior alveolar nerve on the expression of SNS/PN3 mRNA in trigeminal sensory neurons. The organization of sodium channels in the neuronal membrane is maintained by binding to ankyrin, which help link the sodium channel to the membrane skeleton. Ankyrin(G), which colocalizes with sodium channels in the initial segments and nodes of Ranvier, and is necessary for normal neuronal sodium channel function, could be essential in the reorganization of the axonal membrane after nerve injury. For this reason, we here study the expression of ankyrin(G) in the trigeminal ganglion and the localization of ankyrin(G) protein in the inferior alveolar nerve after injury. We show that SNS/PN3 mRNA is down-regulated in small-sized trigeminal ganglion neurons following inferior alveolar nerve injury but that, in contrast to the persistent loss of SNS/PN3 mRNA seen in dorsal root ganglion neurons following sciatic nerve injury, the levels of SNS/PN3 mRNA appear to normalize within a few weeks. We further show that the expression of ankyrin(G) mRNA also is downregulated after nerve lesion and that these changes persist for at least 13 weeks. This decrease in the ankyrin(G) mRNA expression could play a role in the reorganization of sodium channels within the damaged nerve. The changes in the levels of SNS/PN3 mRNA in the trigeminal ganglion, which follow the time course for hyperexcitability of trigeminal ganglion neurons after inferior alveolar nerve injury, may contribute to the inappropriate firing associated with sensory dysfunction in the orofacial region.

Animals↗

PubMed2000

A population analysis of nebulized (R)-albuterol in dogs using a novel mixed gut-lung absorption PK-PD model.

PURPOSE: The objectives of this study were to 1) construct a pharmacokinetic-pharmacodynamic (PK-PD) model, and 2) determine the PKs and PDs of (R)-albuterol when given by nebulization to 8 dogs for 7 consecutive days. METHODS: Four doses were evaluated (0.002, 0.02, 0.1, and 0.4 mg/kg/ day). Blood samples were obtained after drug administration on days 1 and 7. Heart rates (HR) were obtained during treatment days 1, 4 and 7. All (R)-albuterol plasma concentrations were fitted using a mixed gut-lung absorption 2-compartment PK model. Day-1, 4, and 7 HR data were co-modeled using a direct response model with Hilltype equations, including a necessary tolerance phenomenon. The population PK-PD analysis was performed with an iterative 2-stage methodology (IT2S). RESULTS: No chiral inversion was seen, and double absorption peaks on the plasma concentration versus time curves were observed in the majority of dogs. These were hypothesized to be the result of combined gut and lung absorption of (R)-Albuterol. Results indicated that 67% (range: 57-89%) of (R)-albuterol systemic exposure after nebulized administration is due to gut absorption. Mean population PK parameters were KaGI (10+/-5.7 h(-1)), KaLUNG (21+/-9.5 h(-1)), CLc/F (0.6+/-0.2 L/h/kg), CLd/F (1.4+/-0.5 L/h/kg), Vc/F (1.4+/-0.9 L/kg), and Vp/F (4.8+/-2.4 L/kg). (R)-albuterol administration was associated with an increase in the dogs heart rates. A tolerance effect related to the cumulative dose was observed and modeled. CONCLUSIONS: The presented PK-PD model appears to differentiate gut from lung absorption when (R)-albuterol is given by 15-minute nebulization to dogs. These results agree with the accepted hypothesis that most of the systemic exposure of (R)-albuterol after nebulized administration is due to gut absorption.

Administration, Inhalation↗

PubMed2000

Molecular signaling and pulpal nerve development.

The purpose of this review is to discuss molecular factors influencing nerve growth to teeth. The establishment of a sensory pulpal innervation occurs concurrently with tooth development. Epithelial/mesenchymal interactions initiate the tooth primordium and change it into a complex organ. The initial events seem to be controlled by the epithelium, and subsequently, the mesenchyme acquires odontogenic properties. As yet, no single initiating epithelial or mesenchymal factor has been identified. Axons reach the jaws before tooth formation and form terminals near odontogenic sites. In some species, local axons have an initiating function in odontogenesis, but it is not known if this is also the case with mammals. In diphyodont mammals, the primary dentition is replaced by a permanent dentition, which involves a profound remodeling of terminal pulpal axons. The molecular signals underlying this remodeling remain unknown. Due to the senescent deterioration of the dentition, the target area of tooth nerves shrinks with age, and these nerves show marked pathological-like changes. Nerve growth factor and possibly also brain-derived neurotrophic factor seem to be important in the formation of a sensory pulpal innervation. Neurotrophin-3 and -4/5 are probably not involved. In addition, glial cell line-derived neurotrophic factor, but not neurturin, seems to be involved in the control of pulpal axon growth. A variety of other growth factors may also influence developing tooth nerves. Many major extracellular matrix molecules, which can influence growing axons, are present in developing teeth. It is likely that these molecules influence the growing pulpal axons.

Animals↗

PubMed1999

Sodium channel expression in NGF-overexpressing transgenic mice.

Dorsal root ganglion (DRG) neurons depend on nerve growth factor (NGF) for survival during development, and for the maintenance of phenotypic expression of neuropeptides in the adult. NGF also plays a role in the regulation of expression of functional sodium channels in both PC12 cells and DRG neurons. Transgenic mice that overexpress NGF under the keratin promoter (hyper-NGF mice) show increased levels of NGF in the skin from embryonic day 11 through adulthood, hypertrophy of the peripheral nervous system and mechanical hyperalgesia. We show here that mRNA levels for specific sodium channel isotypes are greater in small (< 30 microm diameter) DRG neurons from hyper-NGF mice compared to wild-type mice. Hybridization signals for sodium channel subunits alphaII and beta2 displayed the most substantial enhancement in hyper-NGF mice, compared to wild-type mice DRG, and mRNA levels for alphaI, NaG, Na6, SNS/PN3, NaN, and beta1 were also greater in hyper-NGF DRG. In contrast, the levels of alphaII and PN1 mRNAs were similar in neurons from hyper-NGF and wild-type DRG. Whole-cell patch-clamp studies showed no significant differences in the peak sodium current densities in hyper-NGF vs. wild-type DRG neurons. These data demonstrate that DRG neurons in wild-type mice have a heterogeneous pattern of sodium channel expression, which is similar to that previously described in rat, and suggest that transcripts of some, but not all, sodium channel mRNAs can be modulated by long-term overexpression of NGF.

Animals↗

PubMed1999

Differential role of GDNF and NGF in the maintenance of two TTX-resistant sodium channels in adult DRG neurons.

Following sciatic nerve transection, the electrophysiological properties of small dorsal root ganglion (DRG) neurons are markedly altered, with attenuation of TTX-R sodium currents and the appearance of rapidly repriming TTX-S currents. The reduction in TTX-R currents has been attributed to a down-regulation of sodium channels SNS/PN3 and NaN. While infusion of exogenous NGF to the transected nerve restores SNS/PN3 transcripts to near-normal levels in small DRG neurons, TTX-R sodium currents are only partially rescued. Binding of the isolectin IB4 distinguishes two subpopulations of small DRG neurons: IB4+ neurons, which express receptors for the GDNF family of neurotrophins, and IB4- neurons that predominantly express TrkA. We show here that SNS/PN3 is expressed in approximately one-half of both IB4+ and IB4- DRG neurons, while NaN is preferentially expressed in IB4+ neurons. Whole-cell patch-clamp studies demonstrate that TTX-R sodium currents in IB4+ neurons have a more hyperpolarized voltage-dependence of activation and inactivation than do IB4- neurons, suggesting different electrophysiological properties for SNS/PN3 and NaN. We confirm that NGF restores SNS/PN3 mRNA levels in DRG neurons in vitro and demonstrate that the trk antagonist K252a blocks this rescue. The down-regulation of NaN mRNA is, nevertheless, not rescued by NGF-treatment in either IB4+ or IB4- neurons and NGF-treatment in vitro does not significantly increase the peak amplitude of the TTX-R current in small DRG neurons. In contrast, GDNF-treatment causes a twofold increase in the peak amplitude of TTX-R sodium currents and restores both SNS/PN3 and NaN mRNA to near-normal levels in IB4+ neurons. These observations provide a mechanism for the partial restoration of TTX-R sodium currents by NGF in axotomized DRG neurons, and demonstrate that the neurotrophins NGF and GDNF differentially regulate sodium channels SNS/PN3 and NaN.

Age Factors↗

PubMed1999

Abnormal expression of SNS/PN3 sodium channel in cerebellar Purkinje cells following loss of myelin in the taiep rat.

Using in situ hybridization and immunochemical methods, we have observed an increase in the expression of SNS/PN3 sodium channel mRNA and protein in cerebellar Purkinje cells of the taiep rat. These changes are present in taiep rats at 12 months of age, following loss of myelin, but not at one month, prior to loss of myelin. Increased SNS/PN3 expression is not associated with aging per se, because it was not observed in control rats at 12 months of age. These results suggest that altered sodium channel expression in Purkinje cells may contribute to the ataxia that occurs in taiep rats.

Aging↗

PubMed1999

Reactivation of Delta-Notch signaling after injury: complementary expression patterns of ligand and receptor in dental pulp.

The evolutionarily conserved Notch-mediated intercellular signaling pathway is essential for proper embryonic development of many tissues and organs. Recent data suggest that Notch receptors and their membrane-bound ligands Delta and Serrate are involved in both patterning and cell fate determination during odontogenesis. It remains, however, uncertain if Notch signaling is important for tooth homeostasis and regeneration. Here we report on the expression of Notch receptors and the Delta1 ligand in dental pulp of normal and injured adult rat teeth. Notch receptors were absent from normal adult dental tissues, whereas expression was upregulated after injury. In injured teeth, Notch2 was expressed in mesenchymal cells of the pulp both close to the site of injury (i.e., in the dental crown) and at a distance from it (i.e., in the dental roots), Notch3 expression was mainly associated with vascular structures, while Notch1 expression was restricted to few pulpal cells close to the lesion. None of them was expressed in odontoblasts. Expression of Delta1 was upregulated in odontoblasts of the injured teeth, as well as in vascular structures. These results demonstrate the reactivation of the Notch signaling pathway during wound healing and, furthermore, highlight the similarity between developmental and regenerative processes.

Animals↗

PubMed1999

Sympathetic nerve sprouting fails to occur in the trigeminal ganglion after peripheral nerve injury in the rat.

Peripheral nerve injury induces sprouting of sympathetic nerve fibers in dorsal root ganglia after spinal nerve injury. In the present study, we sought to determine the extent of intraganglionic noradrenergic sprouting in the trigeminal system. The inferior alveolar nerve, a major branch of the mandibular division, or the infraorbital nerve of the maxillary division was either ligated or chronically constricted in Sprague-Dawley rats and recovery permitted for either 2-3 or 6-9 weeks. In some animals both nerves were injured. Using immunohistochemistry with tyrosine hydroxylase antibodies, we found no signs of sympathetic nerve fiber sprouting in the trigeminal ganglion after injury. In contrast, sciatic nerve injury in rat littermates induced a widespread autonomic nerve outgrowth in affected DRGs. Thus, sensory ganglion sympathetic nerve sprouting does not seem to be a general outcome of PNS injury, but is restricted to certain specific locations. Sympathetic nerve fiber networks that surround primary sensory neurons have been suggested to form a structural basis for interactions between the sympathetic and sensory nervous systems after PNS injury. Such interactions, sometimes resulting in paraesthesia or dysaesthesia in patients, appear to be less common in territories innervated by the trigeminal nerve than in spinal nerve regions. The lack of injury-induced intraganglionic sympathetic sprouting in the trigeminal ganglion may help to explain this observation.

Animals↗

PubMed1999

Tooth pulp tissue promotes neurite outgrowth from rat trigeminal ganglia in vitro.

The mammalian tooth pulp becomes innervated by nociceptive and sympathetic axons relatively late during development, when part of the root has formed. In the adult, regenerating axons from an injured tooth nerve or sprouting axons from uninjured nerves in the vicinity rapidly reinnervate denervated tooth pulps. These observations indicate that tooth pulp tissue can use molecular factors to attract pulpal axons from local nerve trunks. The present study examines the hypothesis that these factors include nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and glial cell line derived neurotrophic factor (GDNF). Explants of trigeminal ganglia from neonatal rat pups showed a distinct neurite outgrowth when co-cultured with pulpal explants collected from molar teeth of 12-day old pups, or after application of a pulpal extract. Control cultures, containing single ganglionic explants, or explants co-cultured with heat-treated pulpal tissue, exhibited a sparse neurite outgrowth. Exogenous NGF and/or GDNF, but not exogenous BDNF, stimulated neurite outgrowth from ganglionic explants. Unexpectedly, application of antibodies against NGF, BDNF and/or GDNF to co-cultures of ganglionic and pulpal explants did not inhibit neuritogenesis. Control experiments showed that IgG molecules readily penetrate the gel used for culture and that even very high concentrations of NGF and GDNF antibodies in combination failed to block neurite growth. On the basis of these data we suggest that other as yet unknown neurite-promoting factors might be present and active in TG/pulpal co-cultures.

Animals↗