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DESCRIPTION: Vestibular compensation animation produced for Johnson & Johnson.
The Vestibular system comprises of vestibular apparatus & vestibular nuclei. Situated in the Brain stem, vestibular nuclei plays a central & critical role.
Commissural fibers crossing the midline connect the paired nuclei, ensuring bilateral coordinated functioning of the vestibular system.
The commissural fibers transmit inhibitory impulses between the vestibular nuclei which are essential for maintaining balance in the firing activity. This phenomenon is called Inhibitory commissural mechanism.
In the event of unilateral labrynthine damage, at rest, the ipsilesional vestibular nucleus receives no inputs, while the contralesional nucleus continue receive inputs from the normal labyrinth and becomes hyperactive due to weak inhibitory inputs from ipsilesional vestibular nucleus, this creates an imbalance in the firing rates of the two vestibular nuclei.
This imbalance is further aggravated as ipsilesional vestibular nucleus becomes hypoactive due to continuous inhibitory inputs through commissural inhibition from contralesional vestibular nucleus.
This imbalance results in patients experiencing dizziness/vertigo.
The Natural process of vestibular compensation involves reduction in hyperactivity of contralesional vestibular nuclei and restoration of firing activity in hypoactive ipsilesional vestibular nuclei.
There are four mechanisms, which operate in parallel and synergistically to bring about vestibular compensation.
Mechanisms involved in restoration of firing activity in ipsilesional hypoactive vestibular nucleus.
1. Glycine and GABA are the inhibitory neurotransmitters of the commissural system. At ipsilesional vestibular nucleus down regulation of GABA & glycine receptors results in decreased responsiveness to the inhibitory inputs from contralesional vestibular nucleus.
2. There is upregulation of intrinsic electrophysiological excitability of Ipsilesional vestibular nucleus neurons
3. There is gradual & activity-dependent reorganization of synaptic connectivity. As a result Ipsilesional Vestibular nuclei neuron starts receiving inputs from contralesional side.
Mechanisms involved in reducing the hyperactivity of contralesional vestibular nucleus.
4. Cerebellum exhibits Cerebello-cortical plasticity inhibiting the activity of contralesional Vestibular nuclei neurons resulting in reduction in inhibitory inputs to the Ipsilesional Vestibular nucleus cells.
Let’s explore the role of calcium channel blocker like cinnarizine in vestibular compensation process.
Effect of CCB on intact, Hyperactive Contralesional vestibular nuclei
CCB contributes in reducing the hyperactivity of contralesional vestibular nucleus by 2 mechanisms.
The Central role is attributed to the fact that CCB increases the excitability of GABAnergic Purkinje cells in the cerebellum. This contributes to the cerebellar effect of direct inhibition of Hyperactive Vestibular nuclei on the side of the intact labyrinth.
At labyrinthine level, CCB like Cinnarizine prevents entry of Calcium ions into the vestibular hair cells reducing release of neurotransmitters, resulting in decreased firing frequency. This contributes to reducing the hyperactivity of Contralesional Vestibular nuclei.
Effect of CCB on deafferented, ipsilesional vestibular nuclei
CCB contributes in restoration of firing activity in ipsilesional hypoactive vestibular nucleus.
Deafferentation may cause excessive calcium influx or calcium overload in vestibular neurons. This overload eventually leads to neuronal cell death due to its effect on metabolic processes. This cell death further depresses the resting activity of the ipsilesional vestibular nucleus neurons.
Calcium channel blockers by inhibiting intracellular calcium influx may contribute to the compensation process by preventing the calcium overload and support the recovery of the vestibular nucleus neurons.
Additionally Cinnarizine enhances the responsiveness of vestibular neucleus neurons to vestibular nerve stimulation by improving cerebral and inner ear microcirculation.
Vestibular rehabilitation exercises promote rewiring of synaptic connectivity. Cinnarizine produce selective effect on vestibular system without affecting reticular activating system and thalamo – cortical pathway. Thus it does not impact alertness and vigilance of the patients and may not interfere with vestibular rehabilitation exercises.
Thus cinnarizine may support natural process of vestibular compensation.
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