Galvanic vestibular stimulation modifies vection paths in healthy subjects

The present study aimed at determining whether vestibular inputs contribute to the perception of the direction of self-motion. This question was approached by investigating the effects of binaural bipolar galvanic vestibular stimulation (GVS) on visually induced self-motion (i.e., vection) in healthy subjects. Stationary seated subjects were submitted to optokinetic stimulation inducing either forward or upward linear vection. While perceiving vection, they were administered trapezoidal GVS of different intensities and ramp durations. Subjects indicated the shape and direction of their perceived self-motion path throughout the experiment by a joystick, and after each trial by the manipulation of a 3D mannequin. Results show that: 1) GVS induced alterations of the path of vection; 2) these alterations occurred more often after GVS onset than after GVS offset; 3) the occurrence of vection path alterations after GVS onset depended on the intensity of GVS but not on the steepness of the GVS variation; 4) the vection path deviated laterally according to either an oblique or a curved path; and 5) the vection path deviated toward the cathode side after GVS onset. It is the first time that vestibular information, already known to contribute to the induction of vection, is shown to modify self-motion perception during the course of vection.     

Neurotensin receptor activation sensitizes to the locomotor stimulant effect of cocaine: a role for NMDA receptors

This study was aimed at determining whether repeated activation of neurotensin receptors sensitizes to cocaine-induced locomotor activity and whether this effect can be prevented by blockade of N-methyl-d-aspartate receptors. Independent groups of male rats were injected on four occasions, every other day (training phase), with vehicle or one of two doses (4 and 8 mg/kg) of the NMDA antagonist CPP [(+/-)-3-(2-carboxypiperazine-4-yl)-propanephosphonic)] followed by an intracerebroventricular injection of 18 nmol/10 microl of d-Tyr[(11)]neurotensin, or its vehicle. Ambulatory, non-ambulatory and vertical movements were measured for 2 h on every test day. One week after the last day of the training phase, locomotor responses to a single injection of cocaine (7.5 mg/kg, ip) were measured in all rats; a second cocaine challenge test was performed 3 weeks post-training. Results show that during the training phase d-Tyr[(11)]neurotensin produced an initial suppression of all locomotor responses followed by an augmentation of ambulatory and non-ambulatory activity compared to controls, effects that were only slightly altered by CPP. Cocaine produced higher ambulatory and non-ambulatory activity in animals pre-exposed to neurotensin than in the vehicle pre-exposed animals, a sensitization effect that was not prevented by CPP at 1 week post-training but that was blocked at 3 weeks at the high dose. When given alone, the low dose of CPP produced an effect very similar to that of neurotensin on cocaine sensitization. These results further confirm that neurotensin plays a role in sensitization to psychostimulant drugs and suggests that NMDA receptors are involved in the long-term effect of exposure to neurotensin.     

Direct and indirect effects of muscimol on medial vestibular nucleus neurones in guinea-pig brainstem slices

Inhibitory amino acids are considered as major transmitters in the vestibular system. Using intracellular recordings in slices, we applied gamma-aminobutyric acid (GABA) and muscimol (a specific agonist of the GABA_A receptor) to the two main types of medial vestibular nucleus neurones (A and B MVNn). In either a high Mg²⁺/low Ca²⁺ solution, or a solution containing tetrodotoxin, all MVNn were hyperpolarized by GABA and muscimol. This indicates that both types of MVNn are endowed with postsynaptic, hyperpolarising GABA_A receptors. In a normal medium, about half of A and B MVNn were, in contrast, depolarised by GABA and muscimol, whereas the remaining cells were hyperpolarised. These results could be due to a modulation by GABA and muscimol of a tonic GABA release in the slice. Such a release was, indeed, suggested by results showing the depolarising effect of either tetrodotoxin (TTX) or bicuculline, when applied alone. The cells that were depolarised by GABA or muscimol in control conditions were always hyperpolarised in the presence of TTX. Our data therefore suggest that GABA acting at GABA_A receptors in the medial vestibular nucleus can play a role either through a postsynaptic hyperpolarising action or indirectly by inhibiting a tonic GABA release, probably resulting from the spontaneous activity of local inhibitory interneurones. A GABAergic regulation of these interneurones could be important in processes of vestibular habituation and/or adaptation.     

Dopaminergic Agonists Have Both Presynaptic and Postsynaptic Effects on the Guinea-pig's Medial Vestibular Nucleus Neurons

A number of studies have indicated a possible interaction between dopamine and the vestibular system. Using intracellular recordings in brainstem slices, we have tested the effects of dopamine and other dopaminergic compounds on guinea-pig medial vestibular nucleus (MVN) neurons. In normal medium, MVN neurons were depolarized by dopamine as well as by (-)quinpirole and piribedil, which are selective D₂ dopaminergic agonists. The dependence of this effect on the presence of D₂ receptors was confirmed by using (-)sulpiride, a D₂ antagonist which blocked the depolarizing effect of dopamine. Dopaminergic D₁ receptors were apparently not involved in this effect since a selective D₁ agonist, SKF-38393, had no effect on MVN neurons and the D₁ antagonist (+) SCH-23390 could not block the effect of dopamine. These depolarizing responses to dopamine must be due to a presynaptic action on terminals that normally release GABA spontaneously on MVN neurons, and tonically maintain them in a state of hyperpolarization. Indeed, such a spontaneous release was demonstrated to occur in the slice since application of bicuculline, a GABA_A antagonist, depolarized MVNneurons in normal saline, but not in a high Mg²⁺/low Ca²⁺ solution known to block synaptic transmission. When dopamine was applied in conditions in which no GABA_A-dependent transmission could occur (either in the presence of bicuculline or in a high Mg²⁺/low Ca²⁺ solution) only a hyperpolarizing, most probably postsynaptic, effect occurred. These results indicate that dopamine might exert in vivo a significant modulatory action on the vestibular system, either by a direct action on the vestibular neurons or by modulation of GABAergic transmission.     

Timolol 0.1% gel (Nyogel 0.1% once daily versus conventional timolol 0.5% solution twice daily: a comparison of efficacy and safety

In a prospective, randomised, double-masked, parallel-group, multi-centre study, 210 patients with primary open angle glaucoma or ocular hypertension were enrolled of whom 167 (timolol 0.1% gel 82, timolol 0.5% 85) completed the study as per protocol. The change in intraocular pressure between baseline and week 12 in the worse eye ('at trough') was 6.3 (SD 3.3) mm Hg on timolol 0.1% gel and 7.0 (2.9) mm Hg on timolol 0.5%; this difference was not statistically significant (p = 0.19). The difference between the two study groups in the change of intraocular pressure from baseline was 0.62 mm Hg; the 90% CI of -0.09 to +1.33 mm Hg was within the pre-specified limits of -1.5 to +1.5 mm Hg demonstrating equivalence between timolol 0.1% gel and timolol 0.5%. The plasma levels of timolol (ng/ml) at 12 weeks in the timolol 0.1% gel group were significantly less than that with timolol 0.5% both before instillation (mean 0.057, SD 0.131 and mean 0.470, SD 0.519 respectively, p = 0.025) and after instillation (mean 0.552, SD 0.992 and mean 2.473, SD 1.780 respectively, p = 0.008). Both treatments were well tolerated with no statistically significant difference between the groups in the occurrence of ocular or systemic adverse events.     

Socioeconomic aspects of total hip arthroplasty. A one-year survey in a Belgian university hospital

We prospectively analysed hospital stay, discharge policy, hospital cost and postoperative recovery of 102 consecutive total hip arthroplasties performed in a Belgian university hospital during a one-year period starting in October 2001. Of the independent patients, 87.4% regained independence after 6 weeks and 19.6% used rehabilitation units. Preoperative residence, hip function and mental scores were the best predictors for postoperative independence. Average hospital stay was 14.4 days and hospital cost 9,500 Euros. Hospitalisation represented over 50% of hospital cost and hip implants between 16.1 and 25.6% depending on prosthesis type. Complications and discharge to a rehabilitation unit increased hospital stay and cost. Six months after surgery, functional hip scores as well as WOMAC, mental and physical SF-12 scores improved significantly. Surgical techniques and faster rehabilitation programs, reducing needs for rehabilitation units and allowing earlier return to independence, are probably the best ways to control the cost of total hip arthroplasty in Belgium.     

An in situ hybridization and immunofluorescence study of glycinergic receptors and gephyrin in the vestibular nuclei of the intact and unilaterally labyrinthectomized rat

We investigated whether the expression of glycinergic receptor (GLYR) subunits of gephyrin and of their mRNAs in the medial vestibular nuclei are affected following unilateral labyrinthectomy. Specific radioactive oligonucleotide probes recognizing the sequences encoding 1–3 and ß subunits of GLYR and the anchoring protein gephyrin were used to probe sections of vestibular nuclei. Signals in these in situ hybridization experiments were detected with film or by emulsion photography. Animals were killed at various times following the lesion: 5 h, 1, 3, 8, 30 and 60 days. Specific monoclonal GLYR and gephyrin antibodies were also used to determine GLYR and gephyrin immunoreactivity in control and operated rats (5 h, 1, 3 and 8 days post-lesion). In normal animals, several brainstem regions including the lateral, medial, superior and inferior vestibular nuclei contained mRNAs for gephyrin and the 1 and subunits of GLYR, and expressed the GLYR and gephyrin polypeptides. In unilaterally labyrinthectomized rats, no asymmetry was detected on autoradiographs between the two medial vestibular nuclei with any of the oligonucleotide probes used, or at any time following the lesion. No difference in the immunofluorescence staining was observed between the intact and deafferented medial vestibular nuclei of lesioned animals or between the vestibular nuclei of lesioned and controls rats. Thus, deafferentation of the vestibular nuclei did not affect the expression of gephyrin, of the various GLYR subunits, or of their mRNAs in the deafferented and intact medial vestibular nuclei. It is therefore unlikely that GLYR and gephyrin modulation contribute significantly to the recovery of the resting discharge of the deafferented medial vestibular neurons and consequently to the restoration of a normal posture and eye position.Abbreviations AMPA -amino-3-hydroxy-5-methylisoxazole-4-propionic acid - AF Arithmetic fluorescence - CNS Central nervous system - DTT Dithiothreitol - EGTA Ethylene glycol tetraacetic acid - GABA -aminobutyric acid - GLY Glycine - GLYR Glycine receptors - MVN Medial vestibular nucleus - MVNn Medial vestibular nucleus neurons - OD Optical density - PBS Phosphate buffered saline - mRNA Messenger ribonucleic acid - MVNn Medial vestibular nuclei neurons - NMDA N-methyl-D-aspartate - rAF Relative arithmetic fluorescence - rOD Relative optical density - tRNA Transfer ribonucleic acid - SD Standard deviation - SSC Standard saline citrate - VNn Vestibular nuclei neurons     

Amino acid transporter (VIAAT,VGLUT2) and chloride cotransporter (KCC1, KCC2 and NKCC1) expression in the vestibular nuclei of intact and labyrinthectomized rat

We report the first investigation of whether unilateral labyrinthectomy in adult rats affects the expression of two amino acid transporters, vesicular glutamate transporter 2 (VGLUT2) and vesicular inhibitory amino acid transporter (VIAAT) and of chloride cotransporters (KCC1, KCC2 and NKCC1) in the intact and deafferented medial vestibular nuclei (MVN). In situ hybridization with specific radioactive oligonucleotide probes and immunofluorescent methods were used in normal and unilaterally labyrinthectomized rats at various times following the lesion: 5 h, and 1, 3 and 8 days. In normal animals, several brainstem regions including the lateral, medial, superior and inferior vestibular nuclei contained VGLUT2, VIAAT and KCC2 mRNA. In contrast, no or a very faint labeling was observed with KCC1 and NKCC1 probes. In unilaterally lesioned rats, there was no asymmetry between the two MVN with any of the oligonucleotide probes at any time after the lesion. Similarly, there were no differences in the intensity of MVN labeling between controls and lesioned animals. Finally, no over-expression of the cotransporter KCC1 and NKCC1 was found in ipsilateral or controlateral MVN in lesioned rats at any time. Immunohistochemical experiments gave similar conclusions. Our findings suggest that the recovery of the resting discharge of the deafferented MVN neurons, and consequently the functional compensation of the deficits, are not dependent on changes in the expression of amino acid transporters (VIAAT, VGLUT2), and chloride cotransporters (KCC1, KCC2 and NKCC1) or on their mRNAs.