Stages Of Vestibular Compensation Research Articles

Protective Effects of Hypothalamic Proline-Rich Peptide and Cobra Venom Naja Naja Oxiana on Dynamics of Vestibular Compensation Following Unilateral Labyrinthectomy

We tested the action of proline-rich peptide (PRP-1) and cobra venom Naja Naja Oxiana (NOX) on Deiters' nucleus neurons at 3rd, 15th and 35th days after unilateral labyrinthectomy (UL). Early and late tetanic, post-tetanic potentiation and depression of Deiters'neurons to bilateral high frequency stimulation of hypothalamic supraoptic and paraventricualar nuclei was studied. The analysis of spike activity was carried out by mean of on-line selection and special program. The complex averaged peri-event time and frequency histograms shows the increase of inhibitory and excitatory reactions of Deiters' neurons at early stage of vestibular compensation following PRP-1 and NOX injection, reaching the norm at the end of tests. In histochemical study the changes in Ca(2+)-dependent acidic phosphatase (AP) activity in neurons was discovered. It was shown that in UL animals the total disappearance or delay of decolorizing of Deiters' neurons lead to neurodegenerative pattern as cellular "shade". AP activity after UL and PRP-1 injection exerts more effective recovery of neurons in comparison with events, observed after the administration of NOX. The data of this study indicate that PRP-1 and NOX are protectors, which may successfully recover the disturbed vestibular functions.

Proteomic analysis of the rat cerebellar flocculus during vestibular compensation

Unilateral labyrinthectomy (UL) in rats is used as a human vertigo model. In this model, spontaneous nystagmus and dysequilibrium caused by UL are ameliorated within 48-72 hours. The amelioration, termed vestibular compensation (VC), is long lasting. Although cerebellar flocculi have been reported to be involved in VC, the molecular mechanisms behind VC are unknown. In this study, we used 2D-DIGE to detect protein changes in flocculi during acute (48 hours) and chronic (1 week) stages of VC. We found 99 out of 967 protein spots that showed significant changes in their intensities. Of the 99 spots, 45 spots (ipsilateral side, 15; contralateral side, 30) changed unilaterally during the acute stage, whereas 46 spots (ipsilateral side, 21; contralateral side, 25) changed unilaterally during the chronic stage. Thus, the acute compensation mechanism is more complicated in the contralateral flocculus than in the ipsilateral flocculus. Using MALDI-TOF MS, we identified 10 proteins out of the 12 protein spots. Of these, 3 proteins involved in synaptic transmission, neuronal filament formation and vesicular transport, respectively, demonstrated altered expression only in the acute stage. Our results enhance the understanding of the role of the cerebellar flocculi in VC generation.

11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Medial Vestibular Nucleus and Cerebellum after Unilateral Vestibular Deafferentation in the Rat

In the early stages of vestibular compensation (VC) (the behavioural recovery that follows unilateral vestibular deafferentation), neurons in the medial vestibular nucleus (MVN) on the lesioned side develop a sustained up-regulation of their intrinsic excitability. This plasticity is dependent on the activation of glucocorticoid receptors, which presumably occurs during the acute stress response that accompanies the vestibular deafferentation symptoms. Recent studies have established that the access of glucocorticoids to their intracellular receptors in brain is potently modulated by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), which catalyses the generation of active glucocorticoids from their inert 11-keto forms. In this study, we investigated the presence of 11β-HSD1 bioactivity, and possible changes in activity in the early stage after vestibular deafferentation, in the cerebellar nodulus and uvula, the flocculus/paraflocculus (F/PF) complex and the MVN of the rat. 11β-HSD1 activity was found in each of these brain areas, with especially high levels of activity in the F/PF complex. No differences were found in the level of 11β-HSD1 activity in these brain areas between control rats, sham-operated rats and rats that underwent VC for 4 h after unilateral vestibular deafferentation. These findings demonstrate 11β-HSD1 bioactivity in the MVN and vestibulocerebellum, but exclude the possibility that changes in 11β-HSD1 activity occur in the early period after deafferentation, over the time when changes in MVN neuronal properties take place.

Comparison of protein kinase activity and protein phosphorylation in the medial vestibular nucleus and prepositus hypoglossi in labyrinthine-intact and labyrinthectomized guinea pigs

The aim of the present study was to compare in vitro protein expression, protein kinase activity and protein phosphorylation in the medial vestibular nucleus (MVN) and prepositus hypoglossi (PH) from labyrinthine-intact guinea pigs and from guinea pigs at various stages of vestibular compensation following unilateral labyrinthectomy (UL). The ipsilateral (I-MVN) and contralateral (C-MVN) MVN, and the ipsilateral (I-PH) and contralateral (C-PH) PH, were dissected from 3 naive labyrinthine-intact guinea pigs and 55 guinea pigs at 10 hs or 53 hs following a surgical UL or sham operation. Tissue extracts were incubated with [gamma-33P]ATP+/-Ca2+, phorbol 12, 13 dibutyrate and phosphatidylserine or +/- Ca2+ and calmodulin, to enhance protein kinase C (PKC) or calcium calmodulin kinase (CaMK) activity, respectively. Data were analysed as the ratio of activated to basal 33P incorporation detected by phosphorimaging. There were similar total protein and phosphoprotein profiles in the MVN and PH, as well as both PKC and CaMKII activity, suggesting that the MVN and PH are similar in the way that proteins undergo rapid modification by phosphorylation. During the development of vestibular compensation, a 46 kDa band in C-PH displayed higher PKC-mediated phosphorylation from 10 hs post-UL compared to sham controls. Significantly greater PKC-mediated phosphorylation of proteins of approximately 18, 46 and 75 kDa was observed in C-PH at 10 hs compared to 53 hs post-UL and in most cases the phosphorylation was greater in C-PH than in the C-MVN. These results suggest that between 10 and 53 hs post-UL, PKC-mediated phosphorylation changes mainly in the C-PH rather than the ipsilateral or contralateral MVN.

Plastic changes underlying vestibular compensation in the guinea-pig persist in isolated, in vitro whole brain preparations

Vestibular compensation for the postural and oculomotor deficits induced by unilateral labyrinthectomy is a model of post-lesional plasticity in the central nervous system. Just after the removal of one labyrinth, the deafferented, ipsilateral vestibular nucleus neurons are almost silent, and the discharge of the contralateral vestibular nucleus neurons is increased. The associated static disorders disappear in a few days, as normal activity is restored in both vestibular nuclei. In this study, we searched for traces of vestibular compensation in isolated whole brains taken from adult guinea-pigs. The electrophysiological responses evoked in control brains were compared to those evoked in brains taken from animals that had previously been labyrinthectomized. Guinea-pigs compensated for an initial labyrinthectomy within three days. In vivo, subsequent deafferentation of vestibular nucleus neurons on the intact side triggered “Bechterew's phenomenon”: a new postural and oculomotor syndrome appeared, similar to the one induced by the first lesion, but directed to the newly deafferented side. These disturbances would be caused by the new imbalance between the discharges of neurons in the two vestibular nuclei triggered by the second deafferentation. Experiments were designed to search for a similar imbalance in vitro in brains taken from labyrinthectomized animals, where the intact vestibular nerve is cut during the dissection. Isolated whole brains were obtained from young guinea-pigs at various times (one to seven days) following an initial labyrinthectomy. An imbalance between the resting activities of medial vestibular nucleus neurons on both sides of the brainstem was revealed in brains taken more than three days after the lesion: their discharge was higher on the compensated, initially lesioned side than on the newly deafferented side. In some cases, an oscillatory pattern of discharge, reminiscent of the spontaneous nystagmus associated in vivo with Bechterew's syndrome, appeared in both abducens nerves. These data demonstrate that most of the changes underlying vestibular compensation persist, and can thus be investigated in the isolated whole brain preparation. Brains removed only one day after the lesion displayed normal commissural responses and symmetric spinal inputs to vestibular nucleus neurons. However, an unusually large proportion of the neurons recorded on both sides of the preparation had very irregular spontaneous discharge rates. These data suggest that the first stages of vestibular compensation might be associated with transient changes in the membrane properties of vestibular nucleus neurons. Brains taken from compensated animals displayed a significant, bilateral decrease of the inhibitory commissural responses evoked in the medial vestibular nucleus by single-shock stimulation of the contralateral vestibular nerve. The sensitivity of abducens motoneurons on the initially lesioned, compensated side to synaptic activation from the contralesional vestibular nucleus neurons was also decreased. Both changes may explain the long-term, bilateral decrease of vestibular-related reflexes observed following unilateral labyrinthectomy. Spinal inputs to vestibular nucleus neurons became progressively asymmetric: their efficacy was increased on the lesioned side and decreased on the intact one. This last modification may support a functional substitution of the deficient, vestibular-related synergies involved in gaze and posture stabilization by neck-related reflexes.

Short-term changes in neck muscle and eye movement responses following unilateral vestibular neurectomy in the cat.

The purpose of this study was to investigate changes in neck muscle and eye movement responses during the early stages of vestibular compensation (first 3 weeks after unilateral vestibular neurectomy, UVN). Electromyographic (EMG) activity from antagonist neck extensor (splenius capitis) and flexor (longus capitis) muscles and eye movements were recorded during sinusoidal visual and/or otolith vertical linear stimulations in the 0.05-1 Hz frequency range (corresponding acceleration range 0.003-1.16 g) in the head-fixed alert cat. Preoperative EMG activity from the splenius and longus capitis muscles showed a pattern of alternate activation of the antagonist neck muscles in all the cats. After UVN, two motor strategies were observed. For three of the seven cats, the temporal activation of the individual neck muscles was the same as that recorded before UVN. For the other four cats, UVN resulted in a pattern of coactivation of the flexor and extensor neck muscles because of a phase change of the splenius capitis. In both subgroups, the response patterns of the antagonist neck muscles were consistent for each cat independently of the experimental conditions, throughout the 3 weeks of testing. Cats displaying alternate activation of antagonist neck muscles showed an enhanced gain of the visually induced neck responses, particularly in the high range of stimulus frequency, and a gain decrease in the otolith-induced neck responses at the lowest frequency (0.25 Hz) only. By contrast, for cats with neck muscle coactivation, the gain of the visually induced neck responses was basically unaffected relative to preoperative values, whereas otolith-induced neck responses were considerably decreased in the whole range of stimulation. As concerns oculomotor responses, results in the two subgroups of cats were similar. The optokinetic responses were not affected by the vestibular lesion. On the contrary, otolith-induced eye responses showed a gain reduction and a phase lead. Deficits and short-term changes after UVN of otolith- and semicircular canal-evoked collic and ocular responses are compared.

In vitro phosphorylation of medial vestibular nucleus and prepositus hypoglossi proteins during behavioural recovery from unilateral vestibular deafferentation in the guinea pig

Unilateral removal of vestibular nerve input to the vestibular nuclei (e.g. by unilateral labyrinthectomy, UL) results in severe ocular motor and postural disorders which disappear over time (vestibular compensation). We investigated whether recovery of ocular motor function is temporally correlated with changes in protein phosphorylation in the medial vestibular nucleus (MVN) and prepositus hypoglossi (PH; MVN/PH) in vitro. Bilateral MVN/PH were dissected from 48 guinea pigs following decapitation at 10 h, 53 h or 2 weeks post-UL, or -sham operation and frozen. Tissue extracts were incubated with [ γ- 32P]ATP±Ca 2+ plus phorbol 12,13-dibutyrate and phosphatidylserine. UL resulted in a significant bilateral increase in the 32P-incorporation into a 65–85 kDa band (probably the myristoylated alanine-rich C kinase substrate, MARCKS) in compensated animals (53 h post-UL) under conditions which favoured the activation of protein kinase C. Under identical conditions, the labelling of a 42–49 kDa protein (P46) was increased significantly in the bilateral MVN/PH between either 10 h or 53 h and 2 weeks post-UL; there were no significant changes over time in sham controls. These results show that later stages of vestibular compensation are accompanied by changes in the phosphorylation of several likely protein kinase C substrates in the MVN/PH in vitro.

Role of the visual input in recovery of function following unilateral vestibular lesion in the goldfish. I. Short-term behavioural changes

Vestibular compensation, i.e. the partial or complete recovery of function following lesion of a labyrinth, has been suggested to be based on a multisensory substitution process involving vestibular, visual and somatosensory information. Teleost fish would seem ideal subjects for testing this proposal, because equilibrium orientation in the intact animal is largely under the bimodal control of the vestibular and visual systems. The role of the visual input in the compensation of behavioural deficits elicited by hemilabyrinthectomy (HL) was studied in goldfish maintained over the first two postoperative hours under different lighting conditions. HL caused severe postural and locomotory symptoms, which were the same or similar under all lighting conditions. The rate at which the various deficits disappeared, however, was dependent not only on the presence of light but also on its direction of incidence. Animals maintained under overhead illumination reached the criterion of successful compensation (completion of 5-min continuous and unimpaired swimming) within 10 min, whilst under unilateral illumination (90 degrees to the vertical) the time to criterion was significantly increased; animals exposed to illumination from below or infra-red illumination showed little or no signs of compensation up to 2 h after HL. It is concluded (1) that the immediately postoperative stage of vestibular compensation in the goldfish represents an integral part of the recovery process, within which all observable deficits can be compensated with remarkable rapidity; and (2) that the visual input is both necessary and sufficient for the compensation of the immediately postoperative deficits. We term this early stage of recovery the 'acute' phase and consider it to be based on a visual substitution process, whereby the missing labyrinthine input to the (partially) deafferented vestibular neurons is functionally replaced by visual afferents.

Neurochemical changes in the cholinergic system of the rat lateral vestibular nucleus following hemilabyrinthectomy

The neurochemistry of the cholinergic system in the lateral vestibular nucleus (LVN) of the hemilabyrinthectomized rat was studied in view of the previous findings of other research showing that the process of vestibular compensation (VC) following hemilabyrinthectomy can be influenced by the administration of cholinergic agents. At 15 min, 2 h, and 7 days after right hemilabyrinthectomy, animals were killed and the LVNs were removed from sections of the brain stem for various neurochemical measurements. The content of acetylcholine (ACh) and the activity of acetylcholinesterase in the LVN showed no significant changes at any time interval. In contrast, choline acetyltransferase activity decreased slightly in the nucleus on the unoperated side 15 min after the operation. These findings possibly implicate alterations in ACh synthesis in the LVN at an early stage of VC. However, there was no significant alteration in either high-affinity choline transport into the LVN or ACh release from the LVN 15 min after the operation. Furthermore, muscarinic ACh-receptor binding also showed no significant changes. These results suggest that the possible alterations in the function of cholinergic synapses in the course of VC indicated by previous pharmacological studies may take place in regions of the brain other than the LVN.

Central Vestibular Compensation: Effect of the Bilateral Labyrinthectomy on Neural Activity in the Medial Vestibular Nucleus

An attempt was made to reconstruct the central events that occurred in the various stages of vestibular compensation after a bilateral labyrinthectomy in the cat. Bilateral labyrinthectomized cats showed no nystagmus, but had unsteady head movements and wide gaits. Neural activity in both sides of the medial vestibular nuclei (MVN) was depressed during the critical stage of compensation; however, the neural activity was full and normal during the acute and compensated stage. The experimental results suggest that removing crossed inhibitory influence and reducing the cerebellar inhibitory influence by bilateral labyrinthectomy enhances the process of recovering neural activity in the vestibular nuclei during central compensation, and that the contralateral vestibular end organ is not a source of the driving force responsible for regeneration of electrical activity in the deafferented MVN after a unilateral labyrinthectomy.