Morphology of the human cervical vagus nerve: implications for vagus nerve stimulation treatment.

OBJECTIVES: The vagus nerve has gained a role in the treatment of certain diseases by the use of vagus nerve stimulation (VNS). This study provides detailed morphological information regarding the human cervical vagus nerve at the level of electrode implant. RESULTS: Eleven pairs of cervical vagus nerves and four pairs of intracranial vagus nerves were analysed by the use of computer software. It was found that the right cervical vagus nerve has an 1.5 times larger effective surface area on average than the left nerve [1,089,492 ± 98,337 vs 753,915 ± 102,490 µm(2), respectively, (P < 0.05)] and that there is broad spreading within the individual nerves. At the right side, the mean effective surface area at the cervical level (1,089,492 ± 98,337 µm(2)) is larger than at the level inside the skull base (630,921 ± 105,422) (P < 0.05). This could imply that the vagus nerve receives anastomosing and 'hitchhiking' branches from areas other than the brainstem. Furthermore, abundant tyrosine hydroxylase (TH)- and dopamine ß-hydroxylase (DBH)-positive staining nerve fibres could be identified, indicating catecholaminergic neurotransmission. In two of the 22 cervical nerves, ganglion cells were found that also stained positive for TH and DBH. Stimulating the vagus nerve may therefore induce the release of dopamine and noradrenaline. A sympathetic activation could therefore be part of mechanism of action of VNS. Furthermore, it was shown that the right cervical vagus nerve contains on average two times more TH-positive nerve fibres than the left nerve (P < 0.05), a fact that could be of interest upon choosing stimulation side. We also suggest that the amount of epineurial tissue could be an important variable for determining individual effectiveness of VNS, because the absolute amount of epineurial tissue is widely spread between the individual nerves (ranging from 2,090,000 to 11,683,000 µm(2)). CONCLUSIONS: We conclude by stating that one has to look at the vagus nerve as a morphological entity of the peripheral autonomic nervous system, a composite of different fibres and (anastomosing and hitchhiking) branches of different origin with different neurotransmitters, which can act both parasympathetic and sympathetic. Electrically stimulating the vagus nerve therefore is not the same as elevating the 'physiological parasympathetic tone', but may also implement catecholaminergic (sympathetic) effects.

Annual variations of thyroid reactivity following thyrotropin stimulation and circulating levels of thyroid hormones in the frog Rana ridibunda.

Annual variations in plasma concentration and thyroid gland content of thyroid hormones were studied in male Rana ridibunda during 2 consecutive years together with in vitro capacity of the thyroid gland to release thyroxine (T4) following stimulation with bovine thyrotropin (b-TSH). A low thyroidal content of triiodothyronine (T3) (2-4 ng) and T4 (300-400 ng) is found during winter and increases rapidly after hibernation to maximal values of +/- 50 ng T3 and 2000-2500 ng T4 in May-July. Plasma levels of T3 vary between 10 and 15 pg/ml for all months studied except for a low of 5.4 and 5.7 pg/ml in December and March, respectively. Plasma concentrations of T4 are low in winter (100-200 pg/ml) but increase in January, reaching maximal levels in February-March (700-1000 pg/ml). In the first year levels decrease again until August (last observation month) to about 250 pg/ml, whereas in the second year this decrease is more sudden, reaching winter values of 100-200 pg/ml as early as May-June. Thereafter a second increase in plasma concentrations of T4 is observed again with maximal values of 800 pg/ml obtained in October. This biphasic circannual pattern, from two different observations, is also found in the in vitro T4 release capacity of the thyroid glands following stimulation with 100 mU of b-TSH. The maximal release capacity of the thyroid glands following stimulation with 100 mU of b-TSH. The maximal release capacity of the thyroids is present in March and July-August. Minimal release capacities are present in winter but also in April-June.(ABSTRACT TRUNCATED AT 250 WORDS)