Vestibular Stimulation as An Interventional Approach for Cold Water Stress Induced Immunological and Histopathological Changes in Rats

Background: Chronic exposure to stress results in immuno-suppression. The present study was carried out to explore the therapeutic benefits of vestibular stimulation on the immune system of stress-induced Wistar rats. Methods: Stress was intervened in the Wistar rats by cold water swimming method for a period of 14 days. Following stress, caloric vestibular stimulation was induced in the rats by irrigating external auditory meatus bilaterally with hot water (temperature 41oC) for 2 minutes for a period of 15 days and 30 days in respective groups. At the end of the experiment, blood samples were obtained and serum corticosterone, Interleukin 2 (IL2), Immunoglobulin M (IgM) levels were analyzed using ELISA method and histopathology of brain was assessed. Brain CD4 and CD8 cells were analyzed by Immunohistochemistry. Result: Stress significantly increased serum corticosterone, IL2 levels and reduced IgM levels. Stress group showed increased dendritic arborization in prefrontal cortex, neuronal atrophy, nuclear pyknosis with congested blood vessels in hippocampus and mononuclear cell inflammatory infiltrate in hypothalamus. Brain extravascular CD4 and CD8 showed positive in stress group. Caloric vestibular stimulation effectively reduced serum corticosterone levels, histopathological changes, brain extravascular CD4 and CD8 cells and improved IgM in the present study.

The Acute Effects of Time-Varying Caloric Vestibular Stimulation as Assessed With fMRI

We describe preliminary results from the application of time-varying caloric vestibular stimulation (tvCVS) to volunteers during a continuous blood oxygen level dependent (BOLD) functional MRI (fMRI) acquisition, recording baseline, during-tvCVS and post-tvCVS epochs. The modifications necessary to enable the use of this novel device in a 3-Tesla magnetic field are discussed. Independent component analysis (ICA) was used as a model-free method to highlight spatially and temporally coherent brain networks. The ICA results are consistent with tvCVS induction being mediated principally by thermoconvection in the vestibular labyrinth and not by direct thermal effects. The activation of hub networks identified by ICA is consistent with the concept of sensory neuromodulation, which posits that a modulatory signal introduced to a sensory organ is able to traverse the regions innervated (directly and indirectly) by that organ, while being transformed so as to be “matched” to regional neuronal dynamics. The data suggest that regional neurovascular coupling and a systemic cerebral blood flow component account for the BOLD contrast observed. The ability to modulate cerebral hemodynamics is of significant interest. The implications of these initial findings for the use of tvCVS therapeutically are discussed.

Non-Pharmacological Approaches to Headaches: Non-Invasive Neuromodulation, Nutraceuticals, and Behavioral Approaches

Significant side effects or drug interactions can make pharmacological management of headache disorders very difficult. Non-conventional and non-pharmacological treatments are becoming increasingly used to overcome these issues. In particular, non-invasive neuromodulation, nutraceuticals, and behavioral approaches are well tolerated and indicated for specific patient categories such as adolescents and pregnant women. This paper aims to present the main approaches reported in the literature in the management of headache disorders. We therefore reviewed the available literature published between 2010 and 2020 and performed a narrative presentation for each of the three categories (non-invasive neuromodulation, nutraceuticals, and behavioral therapies). Regarding non-invasive neuromodulation, we selected transcranial magnetic stimulation, supraorbital nerve stimulation, transcranial direct current stimulation, non-invasive vagal nerve stimulation, and caloric vestibular stimulation. For nutraceuticals, we selected Feverfew, Butterbur, Riboflavin, Magnesium, and Coenzyme Q10. Finally, for behavioral approaches, we selected biofeedback, cognitive behavioral therapy, relaxation techniques, mindfulness-based therapy, and acceptance and commitment therapy. These approaches are increasingly seen as a valid treatment option in headache management, especially for patients with medication overuse or contraindications to drug treatment. However, further investigations are needed to consider the effectiveness of these approaches also with respect to the long-term effects.

Role of caloric vestibular stimulation in improvement of motor symptoms and inhibition of neuronal degeneration in rotenone model of Parkinson's disease – An experimental study

ObjectiveParkinson's disease (PD) is a progressive neurodegenerative disorder. In order to explore a noninvasive treatment of PD, in the current study the authors evaluated the neuroprotective efficacy of caloric vestibular stimulation (CVS) using the rotenone-induced rat model of PD. The rotenone models of PD are gaining attention due to high reproducibility. It is also considered to be an improved model to exhibit the pathogenesis of PD and test the neuroprotective effect of various therapeutic interventions.Materials and methodsRotenone was i.p. injected (3 mg/kg body weight) to male Wistar albino rats for 21 days to induce PD. As PD is chronic and progressive in nature, the efficacy of chronic CVS intervention was evaluated for 30 days after inducing PD in rats. Motor symptoms were evaluated by assessing locomotor activity in actophotometer, whereas movement analysis was done using Ludolph test and motor coordination was evaluated using rotarod apparatus. The neurochemical and neuropathological changes were also observed in the corpus striatum of rats.ResultsRotenone administration showed decreased locomotor activity, motor coordination and general movement associated with significant (P < 0.05) reduction in dopamine content in the corpus striatum. The immunohistochemical analysis revealed a marked decrease in tyrosine hydroxylase (TH) immunoreactivity in striatal neurons indicating the significant loss of dopaminergic neurons in substantia nigra (SN) following rotenone injection. However, chronic treatment with CVS restored the nerve terminals in the striatum from rotenone damage. CVS treatment improved the dopaminergic system function by restoring dopamine content in the striatum. CVS also improved the motor deformities clearly suggesting the neuroprotective function.ConclusionThe results of the present study suggested CVS to be a safe and simple neuroprotective measure against neurodegenerative changes in PD and a promising noninvasive technique to overcome the motor symptoms associated with it. The findings could be useful for further investigations and clinical applications of CVS in the treatment of PD.

Beneficial effects of long term caloric vestibular stimulation on changes in brain neurotransmitter dopamine and locomotor activity in Parkinson’s Disease induced rats

Parkinson's Disease (PD) is a neurodegenerative disorder caused due to deficiency of Dopamine in the Substantia nigra. The existing pharmaceutical treatments are not meeting the need, whereas deep brain stimulation is not suitable for patients with co-morbidities. Therefore, a need for non-invasive and conventional treatment with fewer side effects is required. So we have tried a simple method of Caloric Vestibular Stimulation (CVS) for the long term and assessed its neuroprotective effect in PD induced rats. In the present study, 30 adult male Wistar albino rats (250 - 300g) were randomly assigned into five groups. Group 1 control, Group 2 was induced with Parkinson’s disease using rotenone, Group 3 was PD induced and CVS gave for 45 days, Group 4 was PD induced for 21 days and left untreated to study for its recovery, Group 5 was given CVS only for 45 days. The behavioral activity was recorded using an actophotometer and to assess the function of the nigrostriatal pathway. Dopamine produced in the striatum was measured using reverse-phase HPLC. Results showed significant (P< 0.05) alteration in dopamine and locomotor activity in PD, which was significantly (P< 0.05) improved by warm water CVS administration in Parkinson's disease-induced rat. In this aspect, CVS can be utilized as a conventional treatment method for PD and thus recommended for further investigations towards translational treatment in humans for Parkinson’s disease.