Disorder of the saliva melatonin circadian rhythm in patients with Meniere's disease.

OBJECTIVES: Stress is involved in the development of symptoms of Meniere's disease (MD). Stress-related disease has been reported to be associated with disorders in the circadian rhythm of melatonin (MEL) which regulates that rhythm. We therefore investigated MEL circadian rhythm of patients with MD. PATIENTS AND METHODS: A comparison of 13 MD patients was made with age-matched controls. Saliva samples were collected every 3 h. A statistical analysis of the circadian rhythm of saliva MEL was performed for a circadian rhythm by the fit of a 24- and 12-h composite cosine model. In addition, we assessed the stress and depression status of the two groups. RESULTS: The rhythmic amplitude of MEL in the MD group was significantly lower than that in the control group (P < 0.05). The acrophase in the MD group was significantly earlier than that in the control group (P < 0.05). MD patients had significantly higher stress score and depression score than control subjects (P < 0.05). The amplitude in MD patients had no significant correlation with their otologic clinical data. CONCLUSIONS: These results suggest that MD patients have a MEL deficiency, which is related to their stress and depression status rather than the otologic pathological status of MD.

The association of antidiuretic hormone levels with an attack of Meniere's disease.

OBJECTIVES: An elevation of the plasma antidiuretic hormone (ADH) levels has frequently been observed in Meniere's disease patients. However, little is known regarding the mechanism behind such an elevation of ADH level in Meniere's disease patients. Therefore, we measured the plasma ADH in Meniere's disease patients and other vertigo patients to elucidate the association between the ADH levels, stress levels and the development of Meniere's symptom. DESIGN AND SETTING: The plasma ADH levels and plasma osmotic pressure were determined in 23 definite Meniere's disease patients and 160 patients with other types of vertigo/dizziness. All participants were administered questionnaire regarding their psychological status including their stress levels. RESULTS: The ADH levels of Meniere's disease patients in the acute phase (5.80 +/- 1.37 pg/mL) were significantly higher in comparison with that of Meniere's disease patients in the remission phase (2.26 +/- 0.41 pg/mL) (P < 0.05). In other peripheral vertigo patients, the ADH level in the acute phase (1.71 +/- 0.23 pg/mL) was not significantly different from that in the remission phase (1.45 +/- 0.15 pg/mL). Meniere's disease patients in the acute phase had a significantly higher stress score (114 +/- 23) than Meniere's disease patients in the remission phase (56 +/- 13) (P < 0.05). However, there was no significant correlation between their stress score and the ADH levels. CONCLUSIONS: These results suggest that the elevation of the plasma ADH levels in Meniere's disease patients in the acute phase is, therefore, associated with the pathogenesis of Meniere's disease attacks rather than with stress.

Segment-specific branching patterns of single vestibulospinal tract axons arising from the lateral vestibular nucleus in the cat: A PHA-L tracing study.

The purpose of the present study was to detail the spinal cord (SC) trajectories and arborization patterns of vestibulospinal axons descending from the lateral vestibular nucleus (LVN). An anterograde neural tracer, Phaseolus vulgaris-leucoagglutinin (PHA-L), was focally injected into the right-side LVN in 8 cats. Their subsequent survival times varied from 4 days to 12 weeks. The labeled axons were found mainly in the brainstem after 4-5 days and in successively more caudal spinal segments after longer survival times: i.e., in C1-T2 after 2-3 weeks, in C3-T11 after 6-7 weeks, and in T7-S1 after 10-12 weeks. The trajectories of 28 single, thick (diameter >/=2.4 microm) lateral vestibulospinal tract (LVST) axons were traced from serial transverse sections of the SC from C1-8 (n = 10), T1-9 (n = 11), and T11-L7 (n = 7). In the cervical segments, the LVST axons gave off collateral fibers, which terminated mainly in Rexed's laminae VII-VIII. The terminal-field patterns of these collaterals differed from one stem axon to another. In the thoracic segments, the terminal-field patterns from a given LVST axon were similar at each segmental level, i.e., a few main branches with or without short side branches. At the L3-5 midlumbar level, the collaterals usually arborized more extensively, such that their terminal fields occupied a much greater region of laminae VII-VIII. In contrast, at the L6-7 lower lumbar level, collaterals arising from thin axons (diameter <1.0 microm) tended to innervate, with even more extensive arborization, the medial part of the lamina VIII. These results revealed common and segment-specific collateral distribution patterns of LVST axons along the full extent of the spinal neuraxis.

Stimulation of a restricted region in the midline cerebellar white matter evokes coordinated quadrupedal locomotion in the decerebrate cat.

In the reflexively standing acute decerebrate cat, we have previously shown that pulse train microstimulation of the hook bundle of Russel in the midline of the cerebellar white matter, through which crossed fastigiofugal fibers decussate, augments the postural tone of neck, trunk, fore-, and hindlimb extensor muscles. In the present study we examined the possible role of such stimulation in evoking locomotion as the animal is supported by a rubber hammock with its feet contacting the moving surface of a treadmill. We were able to provoke well-coordinated, bilaterally symmetrical, fore- and hindlimb movements, whose cycle time and pattern were controlled by appropriate changes in stimulus intensity and treadmill speed. We carefully and systematically mapped this cerebellar locomotor region (CLR) through repeated dorsoventral penetrations with a glass-coated tungsten microelectrode in a single animal and between animals. We found that the optimal locus for evoking locomotion was centered on the midline, at Horsley-Clarke coordinates H0 and P7.0, and extended over a rostrocaudal and dorsolateral range of approximately 0.5 mm. The lowest effective stimulus intensity at the optimal site was in the range of 5-8 microA. Along penetration tracks to left or right of the midline, effective stimulus intensity increased and evoked locomotor patterns were no longer symmetrical, but rather shifted toward the contralateral limbs. In the same animals, controlled locomotion was evoked by stimulating the mesencephalic locomotor region (MLR). With concomitant stimulation of the optimal sites in the CLR and the MLR, each at subthreshold strength, locomotor movements identical to those seen with suprathreshold stimulation of each site alone were evoked. With concomitant stimulation at suprathreshold strength for each site, locomotion became vigorous, with a shortened cycle time. After making ablative lesions at either the CLR or MLR (unilateral or bilateral), controlled locomotion was still evoked at the prior stimulus strength by stimulating the remaining site. Together, these results demonstrate that selective stimulation of the hook bundle of Russel in the midsagittal plane of the cerebellar white matter evokes "controlled" locomotion identical to that evoked by stimulating the MLR. We have shown that the fastigial nucleus is one of the supraspinal locomotion inducing sites and that it can independently and simultaneously trigger brain stem and spinal locomotor subprograms formerly believed to be the domain of various brain stem regions including the MLR and the subthalamic locomotor region.

Morphology of single pontine reticulospinal axons in the lumbar enlargement of the cat: a study using the anterograde tracer PHA-L.

The fine morphology of single pontine reticulospinal axons in the lumbar enlargement was investigated by using an anterograde Phaseolus vulgaris-leucoagglutinin (PHA-L) tracing technique. Localized injections of PHA-L were made into the nuclei reticularis pontis oralis and caudalis in four cats. Following survival periods of 8-9 weeks, PHA-L-labeled axons were found throughout the lumbar enlargement from segments L4 to S2, in which the diameter of labeled axons was 0.6-2.5 microns. From serial transverse sections (50 microns), trajectories of 21 single pontine reticulospinal axons were traced in continuity over distances of 18.9-36.3 mm, corresponding to three to six segments, respectively. All the identified axons gave off multiple (two to nine) axon collaterals along their courses, with mean intercollateral distances of approximately 5-6 mm. Detailed reconstruction of the collateral arborization in the lumbar enlargement showed a high degree of similarity to that of single axons in the cervical enlargement previously reported (Matsuyama et al. [1997] J. Comp. Neurol. 377:234-250). First, axon collaterals arising from a majority (n = 18) of identified axons innervated the gray matter unilaterally, ipsilateral to the parent axons, whereas those from the remaining three axons innervated the gray matter bilaterally. Second, collateral projections terminated mainly in laminae VIII and VII, with the arborization field confined to a narrow rostrocaudal extent (< 1 mm). Third, the termination fields of axon collaterals arising from a given reticulospinal axon were similar at each segmental level and differed from one stem axon to another. These results suggest that the long descending pontine reticulospinal pathway is composed of different types of axons that may innervate the cervical and lumbar enlargements in continuity in a similar manner.

Cerebellar-induced locomotion: reticulospinal control of spinal rhythm generating mechanism in cats.

In a decerebrate cat (locomotor preparation), stimulation of a restricted region along the midline cerebellar white matter has been found to evoke generalized augmentation of postural muscle tone on a stationary surface (Asanome et al. 1998. Neurosci. Res. 30: 257-269) and "controlled" locomotion on the surface of a moving treadmill. Characteristics of cerebellar-evoked locomotion were similar to those of mesencephalic locomotor region-evoked "controlled" locomotion on the same animal. Microinjection of a neural tracer (CTb-HRP) into the lesioned stimulus site of the cerebellar white matter resulted in both retrograde labelling of cells in the fastigial nuclei, bilaterally, and anterograde labeling of fibers descending to the brain stem. These results indicated that the effective cerebellar stimulus site (cerebellar locomotor region) corresponded to the midline region of the hook bundle of Russell (Rasmussen, A. T., 1933. J. Comp. Neurol. 57: 165-197), through which crossed fastigioreticular, fastigiovestibular, and fastigiospinal fibers pass. In this study, contribution of reticulospinal systems to the control of cerebellar-evoked locomotion was extensively studied. By stimulating the cerebellar locomotor region and the MLR in the same animal, a majority of antidromically identified pontomedullary reticulospinal cells were synaptically activated. The results of the present study demonstrated that fastigial cells with crossed fastigioreticular fibers and reticulospinal fibers play a crucial role in the control of posture and locomotion in the locomotor preparation.