Number Of Trigeminal Ganglion Neurons Research Articles

Semaphorin 3A Inhibits Nerve Regeneration During Early Stage after Inferior Alveolar Nerve Transection

Neuroma formation at sites of injury can impair peripheral nerve regeneration. Although the involvement of semaphorin 3A has been suggested in neuroma formation, this detailed process after injury is not fully understood. This study was therefore undertaken to examine the effects of semaphorin 3A on peripheral nerve regeneration during the early stage after injury. Immunohistochemistry for semaphorin 3A and PGP9.5, a general neuronal marker, was carried out for clarify chronological changes in their expressions after transection of the mouse inferior alveolar nerve thorough postoperative days 1 to 7. At postoperative day 1, the proximal stump of the damaged IAN exhibited semaphorin 3A, while the distal stump lacked any immunoreactivity. From this day on, its expression lessened, ultimately disappearing completely in all regions of the transected inferior alveolar nerve. A local administration of an antibody to semaphorin 3A into the nerve transection site at postoperative day 3 inhibited axon sprouting at the injury site. This antibody injection increased the number of trigeminal ganglion neurons labeled with DiI (paired t-test, p < 0.05). Immunoreactivity of the semaphorin 3A receptor, neuropilin-1, was also detected at the proximal stump at postoperative day 1. These results suggest that nerve injury initiates semaphorin 3A production in ganglion neurons, which is then delivered through the nerve fibers to the proximal end, thereby contributes to the inhibition of axonal sprouting from the proximal region of injured nerves in the distal direction. To our knowledge, this is the first report to reveal the involvement of Sema3A in the nerve regeneration process at its early stage.

Peripheral Glial Cell Line-Derived Neurotrophic Factor Facilitates the Functional Recovery of Mechanical Nociception Following Inferior Alveolar Nerve Transection in Rats.

To identify endogenous sources of glial cell line-derived neurotrophic factor (GDNF) at the injury site following inferior alveolar nerve transection (IANX) and to determine whether GDNF signaling promotes the recovery of orofacial pain sensation. Nociceptive mechanical sensitivity of the facial skin was assessed following IANX (n = 10) or sham operation (n = 7). GDNF-positive cells were identified and the amount of GDNF measured in the injured region of IANX rats (n = 10) and in sham rats (n = 10). The number of trigeminal ganglion neurons with regenerated axons and the nociceptive mechanical sensitivity after continuous GDNF administration at the injury site were also assessed in IANX (n = 28) and sham (n = 12) rats. The effect of GDNF neutralization on nociceptive mechanical sensitivity at the injury site was evaluated using a neutralizing antibody (GFRα1 Nab) in four groups: IANX + phosphate-buffered saline (PBS) (n = 6); sham (n = 12); IANX + GDNF (n = 12); and IANX + GDNF + GFRα1 Nab (n = 12). Statistical analyses included one-way and two-way repeated measures analysis of variance followed by post hoc tests or unpaired t tests. The threshold for statistical significance was set at P < .05. Nociceptive mechanical sensitivity was lost over the 5 days following IANX and was recovered by day 13. GDNF was expressed in infiltrating inflammatory cells and had enhanced expression. GDNF administration enhanced axonal regeneration and recovery of nociceptive mechanical sensitivity. GDNF neutralization inhibited the recovery of nociceptive mechanical sensitivity after IANX. GDNF signaling at the injury site facilitates the functional recovery of mechanical nociception following IANX and is an attractive therapeutic target for the functional disturbance of pain sensation.

The number of nociceptors in the trigeminal ganglion but not proprioceptors in the mesencephalic trigeminal tract nucleus is reduced in dystonin deficient dystonia musculorum mice

The trigeminal ganglion (TG) and mesencephalic trigeminal tract nucleus (Mes5) were investigated in wild type and dystonia musculorum ( dt) mice to study the effect of dystonin deficiency on primary sensory neurons in the trigeminal nervous system. At postnatal day 14, the number of TG neurons was markedly decreased in dt mice when compared to wild type mice (43.1% reduction). In addition, dystonin disruption decreased the number of sensory neurons which bound to isolectin B4, and contained calcitonin gene-related peptide or high-affinity nerve growth factor receptor TrkA. Immunohistochemistry for caspase-3 demonstrated that dystonin deficiency induced excess cell death of TG neurons during the early postnatal period. In contrast, Mes5 neurons were barely affected in dt mice. These data together suggest that dystonin is necessary for survival of nociceptors but not proprioceptors in the trigeminal nervous system.

Regeneration of periodontal Ruffini endings of rat lower incisors following nerve cross-anastomosis with mental nerve

The present study utilized protein gene product 9.5 (PGP 9.5) and S-100 protein immunohistochemistry to examine if Ruffini endings, the primary mechanoreceptors in periodontal ligaments, can regenerate following nerve cross-anastomosis with an inappropriate nerve. Normally, axon terminals of periodontal Ruffini endings are extensively ramified, and terminal Schwann cells, identified by their S-100 immunoreactivity, are associated with axon terminals. Schwann cells are restricted to the alveolus-related part (ARP), but not tooth-related part (TRP) or the shear zone at the border between the ARP and the TRP of the lingual periodontal ligament of the lower incisor. When the central portion of the mental nerve (MN) was connected with the peripheral portion of the inferior alveolar nerve (IAN), regenerating MN fibers invaded the IAN around postoperative day 5 (PO 5). During the postoperative period, numerous S-100-immunoreactive (IR) cells, presumably terminal Schwann cells, began to migrate to the shear zone and the TRP. PGP 9.5-IR elements reappeared at PO 7 and gradually increased in number. Around PO 28, the terminal portion of the regenerating Ruffini endings appeared dendritic, but less expanded, and the rearrangement of terminal Schwann cells was noted. Regenerated periodontal Ruffini endings were slightly smaller in number. The number of trigeminal ganglion neurons sending peripheral processes beyond the site of injury was smaller compared to those of normal MN, but their cross-sectional areas were almost comparable. Expressions of calbindin D28k and calretinin, normally localized in axonal elements in Ruffini endings, were first detected around PO 56. The present results show that parts of periodontal Ruffini endings can regenerate following nerve cross-anastomosis with mental nerve.

Mechanisms of Immunization with a Replication-Defective Mutant of Herpes Simplex Virus 1

We have investigated the mechanisms by which subcutaneous immunization of mice with a replication-defective mutant of herpes simplex virus 1 protects against infection of the eye and latent infection of the trigeminal ganglion following corneal challenge. First, we have shown that immunization reduces the number of trigeminal ganglion neurons in challenged animals that express the latency-associated transcript. This indicates that the reduction in the incidence of latent infection by challenge virus is likely due to immune mechanisms and not saturation of the potential sites of latent infection by the immunizing mutant virus itself. Second, the duration of protective immunity against acute infection, keratitis, and latent infection was similar in mice immunized with replication-defective or -competent virus; thus, the replication-defective mutant virus is able to induce durable immunity apparently without spread in the host. Third, although the mutant virus showed no evidence of replicationin vivo,it was present in footpad tissue in an infectious form for several days. This surprising observation raises the possibility that continued infection events by input virus over an extended period of time may have a boosting effect on the developing immune response which could explain, at least in part, the capacity of these replication-defective mutant viruses to elicit a robust and durable immunity despite their inability to spread within the host.