144 - Evaluation of Tyrosine Hydroxylase Immunoreactive Ganglion-Like Cells Within the Human Vagus Nerve

Poster Board Number: 144
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Abstract Body : INTRODUCTION. Recently, the Vagus nerve (VN) has become a notorious target for investigations due to the rising dependability of Vagus Nerve Stimulation (VNS) therapy to treat various conditions such as refractory epilepsy, heart failure, and Parkinson’s disease. The VN is well known as a principal source of preganglionic parasympathetic fibers to the cervical, thoracic, and abdominal viscera. However, the presence of catecholaminergic fibers, presumably postganglionic sympathetic, has been ascertained through immunohistochemical assessment of the VN with anti-tyrosine hydroxylase (TH) antibody. The origin of these fibers remains ambiguous. Previous investigators observed the large cells within VN that morphologically resembled ganglion cells with TH+ cytoplasm. Our study aimed to elucidate the presence and distribution of catecholaminergic vagal ganglion-like cells (GLC) within the cervical VN and to evaluate them as a probable source of TH+ fibers in VN.
METHODS. Cervical VN samples were collected bilaterally from 22 fully embalmed cadavers (male n=12, females n=10) at superior and inferior cervical ganglia levels for histological examination. Superior Cervical Ganglia (SCG) were examined for TH-reactivity to confirm the quality of TH detection in embalmed cadavers. All samples were validated with Luxol Fast Blue, immunohistochemically for TH reactivity, and processed by omitting primary antibody to exclude false positive readings. Neuronal somata that expressed immunoreactivity for TH were identified and photographed. Quantitative analysis of the images was conducted with ImageJ by measuring the nerve's surface area, TH+ area, and the surface area of the neuronal somata. Data were analyzed using PAST 4.11.
RESULTS. Immunohistochemical analysis revealed TH+ fibers within cervical VN in all examined whole-body donors. A total of 44 neuronal somata with eccentric nuclei, surrounded by a layer of cells, was identified in 15 (68%) of examined donors, with 75 % of cells observed in the right superior location. The mean surface area of the GLC within the VN was significantly larger than SCG cells (0.001455 ± 0.000142 mm2 and 0.000537 ±0.000036 mm2, respectively, p < 0.0001). The linear regression showed no statistically significant correlation between the number or total surface area of the GLC and the vagal catecholaminergic component.
CONCLUSION. Our study is the first to provide descriptive and quantitative analysis of the large cells with TH+ cytoplasm morphologically resembling ganglion cells and analyze them as a potential source of TH+ component within the VN. The number or the total surface area of the GLC was not a significant predictor of TH+ saturation within the VN. Therefore, it seems unlikely that GLC is the primary origin of vagal TH+ fibers. Our findings support previous studies regarding the consistent presence of vagal catecholaminergic fibers in the human cervical VN.
SIGNIFICANCE. Knowledge of the sympathetic component of the VN is imperative for a better understanding the mechanisms of therapeutic effects and adverse responses to VNS. The functional tandem of coexisting antagonistic divisions in the VN remains uncertain. The catecholaminergic component within VN can lead to augmented sympathetic outflow to the heart and reduction in the cardioprotective function of parasympathetic influence, thus, increasing cardiovascular risk.