# Pathological Study on Trigeminal Ganglionitis Among Rabid Dogs in the Philippines

**Authors:** Nuttipa Iamohbhars, Alpha Grace B. Cabic, Boonkanit Markbordee, Ryota Shiina, Natsumi Tamura, Nozomi Shiwa-Sudo, Kazunori Kimitsuki, Mark Joseph M. Espino, Daria Llenaresas Manalo, Satoshi Inoue, Chun-Ho Park

PMC · DOI: 10.3390/vetsci12040299 · Veterinary Sciences · 2025-03-24

## TL;DR

This study examines the nerve damage in rabid dogs' trigeminal ganglia, revealing how the rabies virus affects the nervous system and causes neurological symptoms.

## Contribution

The study provides new insights into the histopathological progression of trigeminal ganglionitis in rabid dogs and its correlation with neurological symptoms.

## Key findings

- Trigeminal ganglionitis in rabid dogs is classified into three severity grades based on inflammatory cell infiltration and degeneration.
- Viral antigens are most prominent in mild cases and decrease in severe cases, suggesting progression of the disease.
- HLA-DR-positive cells are primarily involved in neuronophagia and Nageotte nodules, indicating immune response patterns.

## Abstract

Rabies is a zoonotic disease caused by the rabies virus, which is one of the most neurotropic viruses. Brain lesions caused by rabies are characterized by non-suppurative encephalitis and intracytoplasmic inclusions. However, the histopathology of the lesions in the peripheral nervous tissues remains unclear. This study aimed to investigate the histopathology of the trigeminal ganglion in rabid dogs. Ninety-two trigeminal ganglia from rabid dogs were examined. Trigeminal ganglionitis was classified into three grades based on pathological findings: mild (13.0%), moderate (56.5%), and severe (30.4%). The number of inflammatory cell infiltrations, neuronophagia, and Nageotte nodules exhibited a direct correlation with severity. These pathological findings suggest that the rabies virus reaches the trigeminal ganglion via ascending or descending routes and that trigeminal neuropathological changes induced by the rabies virus contribute to neurological symptoms observed in rabid dogs.

The trigeminal nerve is the primary gateway through which the rabies virus enters the brain. Viral infection-related trigeminal neuritis is associated with certain clinical signs. This study investigated trigeminal ganglion histopathology in 92 rabid dogs. Trigeminal ganglionitis was classified into three pathological grades: mild, moderate, and severe. Immunostaining of selected sections was performed using antibodies against lymphocytes (CD3, CD20), stellate cells (glial fibrillary acidic protein, GFAP), macrophages (Iba-1, HLA-DR), ganglion cells (neurofilament, NF), and Schwann cells (S-100) to identify lesion cell types. In moderate and severe cases, double-immunofluorescence staining was performed to determine neuronophagia and Nageotte nodule cell types. Mild (13.0%) cases had minimal morphological changes in ganglion cells; moderate (56.5%) and severe (30.4%) cases showed infected ganglion cells and axons with degenerative necrosis, which were replaced by inflammatory cells. Immunohistochemically, viral antigens were detected in most ganglion cells in mild cases and were significantly reduced in severe cases. The number of CD3-, CD20-, GFAP-, and Iba-1-positive cells increased as the severity progressed, and neuronophagia and Nageotte nodules primarily comprised HLA-DR-positive cells. These findings suggest that the rabies virus reaches the trigeminal ganglion via ascending or descending routes and induces trigeminal neuropathological changes, contributing to neurological symptoms in rabid dogs.

## Linked entities

- **Proteins:** cd.3 (Cd.3 conserved hypothetical protein), MS4A1 (membrane spanning 4-domains A1), GFAP (glial fibrillary acidic protein), AIF1 (allograft inflammatory factor 1), NFASC (neurofascin), S100A1 (S100 calcium binding protein A1)
- **Diseases:** rabies (MONDO:0019173)
- **Species:** Canis lupus familiaris (taxon 9615)

## Full-text entities

- **Genes:** GFAP (glial fibrillary acidic protein) [NCBI Gene 480495], MS4A1 (membrane spanning 4-domains A1) [NCBI Gene 485430] {aka CD20}
- **Diseases:** trigeminal neuritis (MESH:D009443), neurological symptoms (MESH:D009461), Trigeminal Ganglionitis (MESH:D045888), infected (MESH:D007239), Viral infection (MESH:D014777), necrosis (MESH:D009336), inflammatory (MESH:D007249)
- **Species:** Canis lupus familiaris (dog, subspecies) [taxon 9615], Lyssavirus rabies (species) [taxon 11292]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12031245/full.md

## References

44 references — full list in the complete paper: https://tomesphere.com/paper/PMC12031245/full.md

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Source: https://tomesphere.com/paper/PMC12031245