The Vestibular System: A Newly Identified Regulator of Bone Homeostasis Acting Through the Sympathetic Nervous System.

The vestibular system is a small bilateral structure located in the inner ear, known as the organ of balance and spatial orientation. It senses head orientation and motion, as well as body motion in the three dimensions of our environment. It is also involved in non-motor functions such as postural control of blood pressure. These regulations are mediated via anatomical projections from vestibular nuclei to brainstem autonomic centers and are involved in the maintenance of cardiovascular function via sympathetic nerves. Age-associated dysfunction of the vestibular organ contributes to an increased incidence of falls, whereas muscle atrophy, reduced physical activity, cellular aging, and gonadal deficiency contribute to bone loss. Recent studies in rodents suggest that vestibular dysfunction might also alter bone remodeling and mass more directly, by affecting the outflow of sympathetic nervous signals to the skeleton and other tissues. This review will summarize the findings supporting the influence of vestibular signals on bone homeostasis, and the potential clinical relevance of these findings.

Influence of vestibular input on spatial and nonspatial memory and on hippocampal NMDA receptors.

It has recently been shown that a lack of vestibular sensory information decreases spatial memory performance and induces biochemical changes in the hippocampus in rodents. After vestibular neurectomy, patients display spatial memory deficit and hippocampal atrophy. Our objectives were to explore: (a) spatial (Y maze, radial-arm maze), and non-spatial (object recognition) memory performance, (b) modulation of NMDA receptors within the hippocampus using radioligand binding, and (c) hippocampal atrophy, using MRI, in a rat model of bilateral labyrinthectomy realized in two operations. Chemical vestibular lesions (VLs) were induced in 24 animals by transtympanic injections of sodium arsanilate (30 mg/0.1 ml/ear), one side being lesioned 3 weeks after the other. The control group received transtympanic saline solution (0.1 ml/ear) (n = 24). Spatial memory performance (Y maze and radial maze) decreased after VL. Conversely, non-spatial memory performance (object recognition) was not affected by VL. No hippocampal atrophy was observed with MRI, but density of NMDA receptors were increased in the hippocampus after VL. These findings show that the lack of vestibular information induced specific deficits in spatial memory. Additionally, quantitative autoradiographic data suggest the involvement of the glutamatergic system in spatial memory processes related to vestibular information. When studying spatial memory performances in the presence of vestibular syndrome, two-step labyrinthectomy is a suitable procedure for distinguishing between the roles of the specific components of vestibular input loss and those of impaired locomotor activity.

Evaluation of the chemical model of vestibular lesions induced by arsanilate in rats.

Several animal models of vestibular deficits that mimic the human pathology phenotype have previously been developed to correlate the degree of vestibular injury to cognate vestibular deficits in a time-dependent manner. Sodium arsanilate is one of the most commonly used substances for chemical vestibular lesioning, but it is not well described in the literature. In the present study, we used histological and functional approaches to conduct a detailed exploration of the model of vestibular lesions induced by transtympanic injection of sodium arsanilate in rats. The arsanilate-induced damage was restricted to the vestibular sensory organs without affecting the external ear, the oropharynx, or Scarpa's ganglion. This finding strongly supports the absence of diffusion of arsanilate into the external ear or Eustachian tubes, or through the eighth cranial nerve sheath leading to the brainstem. One of the striking observations of the present study is the complete restructuring of the sensory epithelia into a non sensory epithelial monolayer observed at 3months after arsanilate application. This atrophy resembles the monolayer epithelia observed postmortem in the vestibular epithelia of patients with a history of lesioned vestibular deficits such as labyrinthectomy, antibiotic treatment, vestibular neuritis, or Ménière's disease. In cases of Ménière's disease, aminoglycosides, and platinum-based chemotherapy, vestibular hair cells are destroyed, regardless of the physiopathological process, as reproduced with the arsanilate model of vestibular lesion. These observations, together with those presented in this study of arsanilate vestibular toxicity, suggest that this atrophy process relies on a common mechanism of degeneration of the sensory epithelia.

The ventrolateral surgical approach to labyrinthectomy in rats: anatomical description and clinical consequences.

UNLABELLED: Destruction of the inner ear in rats for medical research has been performed since 1936. Nevertheless, descriptions of the technique used and clinical analysis are poor and often involve coagulation of the stapedial artery. We suggest a description of a surgical ventrolateral approach to labyrinthectomy in rats, with preservation of the stapedial artery. METHODS: Twenty-five Wistar rats were operated on via a right ventrolateral approach to the bulla, followed by labyrinthectomy with preservation of the stapedial artery. Clinical observation and tests were carried out from the time of the surgery until day one. Twenty-four hours after the surgery on the right side, the same surgery was performed on the left side, followed by clinical observation. Twenty-five other rats were used as controls, with sham surgery. Histologic analysis of the vestibular nerve with silver staining was performed in six rats 3 or 7 days after the labyrinthectomy. RESULTS: The ventrolateral approach made it possible to reach the middle- and inner-ear with preservation of nervous and vascular elements such as the facial nerve and stapedial artery. Unilateral labyrinthectomy induced ocular skew deviation, head torsion and limb asymmetry. Dynamic signs were first rolling, then rotation, which increased considerably during tail suspension. Bilateral labyrinthectomy produces instability with major body oscillation. Animals show head and neck dorsiflexion with limb extension, sometimes followed by fast backward walking. CONCLUSION: The ventrolateral approach is an efficient technique for surgical labyrinthectomy with stapedial artery preservation. Clinical analysis shows a wide range of signs to evaluate the functional destruction of the vestibular organ.

Sympathetic B antagonist prevents bone mineral density decrease induced by labyrinthectomy.

We previously showed that bilateral vestibular lesion in rats induces a bone loss in weight bearing bones. To determine whether this effect is mediated by the sympathetic nervous system (SNS), bone mineral density (BMD) was measured in 4 groups of 10 female Wistar rats: bilateral labyrinthectomy (Bilab), Bilab with propranolol treatment, sham operated with or withoutpropranolol. In untreated rats, 30 days after lesion Bilab animals showed a reduced BMD in distal femoral metaphysis comparatively to intact rats (p < 0.001). In treated rats, there was no difference in BMD 30 days after lesion. This protective effect of propranolol against bone loss suggests that the vestibular system influence on bone remodeling is mediated by SNS. If this hypothesis is correct, this could have important consequences in devising countermeasures to spaceflight induced bone loss.

DNA evidence: wrong answers or wrong questions?

Much of the controversy over DNA evidence is due to the way in which forensic scientific evidence has classically been presented. The orthodox approach is to consider whether two samples match according to a predetermined criterion. If they do, the fact of match is reported along with an estimate of the frequency of the characteristics. This method fails to address the questions raised in court cases, diverts argument into irrelevancies and stultifies research. Presentation of evidence in the form of likelihood ratios, on the other hand, forces the witness to answer the questions the court is interested in and makes apparent lines of research required to increase our understanding.

Genetic matches and the logic of the law.

In a recent article Levine and Kobilinsky (1997) point out that current methods in forensic DNA 'identification' are inadequate because the commercial kits commonly used in forensic practice do not detect the true genotype, but rather a genotype based on convenient categorization. For this reason, Levine and Kobilinsky argue that statistics attached to such categorizations are invalid. The authors believe that the arguments of Levine and Kobilinsky are logically flawed.