Anat Cell Biol.  2023 Dec;56(4):463-468. 10.5115/acb.23.084.

Histology and immunohistochemistry of the human carotid sinus nerve

• Bryant D
• McCormack E
• Cardona JJ
• Chaiyamoon A
• Shekhawat D
• Reina F
• Carrera A
• Iwanaga J
• Dumont AS
• Tubbs RS

• KMID: 2548899
• DOI: http://doi.org/10.5115/acb.23.084

Abstract

The carotid sinus nerve (CSN) is well known as mediating baroreflexes. However, studies of its detailed histological analysis are scant in the literature. Therefore, the current anatomical study sought to better elucidate the microanatomy of the CSN. Ten fresh frozen adult cadavers underwent dissection of the CSN. Then, it was harvested and submitted for histological and immunohistochemical staining. Specimens were all shown to be nerve fibers on histology and immunohistochemistry. We identified tyrosine hydroxylase positive fibers in all CSN specimens. These fibers were always found to be within the CSN and not on its surface i.e., epineurium. Based on our findings, the majority of fibers contained in the CSN are tyrosine positive in nature. Further studies are necessary to understand the true function of this autonomic nerve fibers.

Keyword

Carotid sinus nerve; Histology; Immunohistochemistry; Nerve stimulation, Anatomy

Figure

• 

  Fig. 1 Schematic drawing of the right side of the neck noting the major nerves. *The carotid sinus nerve. By David Fisher.

• 

  Fig. 2 Right cadaveric dissection noting the CSN. Note its origin from the CN IX. Also, observe the posterior belly of the digastric muscle (reflected laterally), the hypoglossal nerve (reflected laterally), the IJV, ICA, and ECA (cadaveric dissection from Tulane University). CSN, carotid sinus nerve; CN IX, glossopharyngeal nerve; IJV, internal jugular vein; ICA, internal carotid artery; ECA, external carotid artery; PBD, posterior belly of the digastric muscle; CN XII, hypoglossal nerve.

• 

  Fig. 3 Histological imaging (cross section) of the carotid sinus nerve (center of image) (×200; cresyl violet-Luxol fast blue).

• 

  Fig. 4 Longitudinal section of the carotid sinus nerve (neurofilament ×400).

• 

  Fig. 5 (A) Longitudinal (×40) (B) and axial sections (×400) of the carotid sinus nerve both stained with tyrosine hydroxylase.

Reference

References

1. Toorop RJ, Scheltinga MR, Moll FL, Bleys RL. 2009; Anatomy of the carotid sinus nerve and surgical implications in carotid sinus syndrome. J Vasc Surg. 50:177–82. DOI: 10.1016/j.jvs.2009.03.029. PMID: 19563966.

2. Shoja MM, Rai R, Lachkar S, Iboroma Akobo S, Yilmaz E, Loukas M, Binello E, Gorjaian M, Griessenauer CJ, Iwanaga J, Tubbs RS. 2019; The carotid sinus nerve and the first English translation of Hering's original research on this nerve. Cureus. 11:e3898. DOI: 10.7759/cureus.3898. PMID: 30911454. PMCID: PMC6424551.

3. Kikuta S, Iwanaga J, Kusukawa J, Tubbs RS. 2019; Carotid sinus nerve: a comprehensive review of its anatomy, variations, pathology, and clinical applications. World Neurosurg. 127:370–4. DOI: 10.1016/j.wneu.2019.04.064. PMID: 30995553.

4. Andrew K, Iwanaga J, Loukas M, Oskouian RJ, Tubbs RS. 2018; A variant origin of the carotid sinus nerve. Cureus. 10:e2883. DOI: 10.7759/cureus.2883. PMID: 30155385. PMCID: PMC6110416.

5. Porzionato A, Macchi V, Stecco C, De Caro R. 2019; The carotid sinus nerve-structure, function, and clinical implications. Anat Rec (Hoboken). 302:575–87. DOI: 10.1002/ar.23829. PMID: 29663677.

6. Tubbs RS, Wellons JC 3rd, Patwardhan RV, Oakes WJ, Wyss JM. 2002; The effectiveness of Hering's nerve stimulation in controlling penicillin-induced seizures in the rat is dependent on the amygdala. Pediatr Neurosurg. 37:231–4. DOI: 10.1159/000066213. PMID: 12411713.

7. Tubbs RS, Patwardhan RV, Wellons JC 3rd, Oakes WJ. 2002; Cortical representation of Hering's nerve: a possible anatomical pathway for seizure cessation following electrical stimulation. Pediatr Neurosurg. 37:235–9. DOI: 10.1159/000066214. PMID: 12411714.

8. Iwanaga J, Singh V, Takeda S, Ogeng'o J, Kim HJ, Moryś J, Ravi KS, Ribatti D, Trainor PA, Sañudo JR, Apaydin N, Sharma A, Smith HF, Walocha JA, Hegazy AMS, Duparc F, Paulsen F, Del Sol M, Adds P, Louryan S, Fazan VPS, Boddeti RK, Tubbs RS. 2022; Standardized statement for the ethical use of human cadaveric tissues in anatomy research papers: recommendations from Anatomical Journal Editors-in-Chief. Clin Anat. 35:526–8. DOI: 10.1002/ca.23849. PMID: 35218594.

9. Kawagishi K, Fukushima N, Yokouchi K, Sumitomo N, Kakegawa A, Moriizumi T. 2008; Tyrosine hydroxylase-immunoreactive fibers in the human vagus nerve. J Clin Neurosci. 15:1023–6. DOI: 10.1016/j.jocn.2007.08.032. PMID: 18617399.

10. Rees PM. 1967; Observations on the fine structure and distribution of presumptive baroreceptor nerves at the carotid sinus. J Comp Neurol. 131:517–48. DOI: 10.1002/cne.901310409. PMID: 5582293.

11. Boyd JD. 1937; Observations on the human carotid sinus and its nerve supply. Anat Anz. 84:386–99.

12. Dean C, Seagard JL. 1997; Mapping of carotid baroreceptor subtype projections to the nucleus tractus solitarius using c-fos immunohistochemistry. Brain Res. 758:201–8. DOI: 10.1016/S0006-8993(97)00245-X. PMID: 9203549.

13. Seagard JL, van Brederode JF, Dean C, Hopp FA, Gallenberg LA, Kampine JP. 1990; Firing characteristics of single-fiber carotid sinus baroreceptors. Circ Res. 66:1499–509. DOI: 10.1161/01.RES.66.6.1499. PMID: 2344663.

14. Drummond HA, Price MP, Welsh MJ, Abboud FM. 1998; A molecular component of the arterial baroreceptor mechanotransducer. Neuron. 21:1435–41. DOI: 10.1016/S0896-6273(00)80661-3. PMID: 9883735.

15. Finley JC, Polak J, Katz DM. 1992; Transmitter diversity in carotid body afferent neurons: dopaminergic and peptidergic phenotypes. Neuroscience. 51:973–87. DOI: 10.1016/0306-4522(92)90534-9. PMID: 1283213.

16. Yokoyama T, Nakamuta N, Kusakabe T, Yamamoto Y. 2014; Vesicular glutamate transporter 2-immunoreactive afferent nerve terminals in the carotid body of the rat. Cell Tissue Res. 358:271–5. DOI: 10.1007/s00441-014-1921-x. PMID: 24906290.

17. Parry SW. 2020; Should we ever pace for carotid sinus syndrome? Front Cardiovasc Med. 7:44. DOI: 10.3389/fcvm.2020.00044. PMID: 32391383. PMCID: PMC7188762. PMID: 569d52fc080f4695a94e3830c843d15b.

18. Abdala AP, McBryde FD, Marina N, Hendy EB, Engelman ZJ, Fudim M, Sobotka PA, Gourine AV, Paton JF. 2012; Hypertension is critically dependent on the carotid body input in the spontaneously hypertensive rat. J Physiol. 590:4269–77. DOI: 10.1113/jphysiol.2012.237800. PMID: 22687617. PMCID: PMC3473284.

19. Conde SV. 2018; Ablation of the carotid bodies in disease: meeting its adverse effects. J Physiol. 596:2955. DOI: 10.1113/JP275796. PMID: 29388224. PMCID: PMC6068219.

20. Conde SV, Sacramento JF, Melo BF, Fonseca-Pinto R, Romero-Ortega MI, Guarino MP. 2022; Blood pressure regulation by the carotid sinus nerve: clinical implications for carotid body neuromodulation. Front Neurosci. 15:725751. DOI: 10.3389/fnins.2021.725751. PMID: 35082593. PMCID: PMC8784865. PMID: f3562dc55296408193c3035f43ee56c3.

21. Epstein SE, Beiser GD, Goldstein RE, Redwood D, Rosing DR, Glick G, Wechsler AS, Stampfer M, Cohen LS, Reis RL, Braunwald NS, Braunwald E. 1969; Treatment of angina pectoris by electrical stimulation of the carotid-sinus nerves. N Engl J Med. 280:971–8. DOI: 10.1056/NEJM196905012801801. PMID: 4888077.

22. Bisognano JD, Bakris G, Nadim MK, Sanchez L, Kroon AA, Schafer J, de Leeuw PW, Sica DA. 2011; Baroreflex activation therapy lowers blood pressure in patients with resistant hypertension: results from the double-blind, randomized, placebo-controlled rheos pivotal trial. J Am Coll Cardiol. 58:765–73. DOI: 10.1016/j.jacc.2011.06.008. PMID: 21816315.

23. Iwanaga J, Singh V, Ohtsuka A, Hwang Y, Kim HJ, Moryś J, Ravi KS, Ribatti D, Trainor PA, Sañudo JR, Apaydin N, Şengül G, Albertine KH, Walocha JA, Loukas M, Duparc F, Paulsen F, Del Sol M, Adds P, Hegazy A, Tubbs RS. 2021; Acknowledging the use of human cadaveric tissues in research papers: recommendations from anatomical journal editors. Clin Anat. 34:2–4. DOI: 10.1002/ca.23671. PMID: 32808702.