ELECTRICAL STIMULATION CAN RESTORE POSTURAL DISTURBANCE
CAUSED BY VESTIBULAR DISORDERS
Department of Physiology,
Iksan 570-749,
ABSTRACT
This study was proposed to evaluate the effect
of electrical stimulation on restoration of postural disturbance following
unilateral labyrinthectomy in rabbits. Electrical
stimulation with 1-3 V, 0.1 ms, 100 Hz was applied to the lesioned
vestibular system by means of gyrosensor. Vestibuloocular reflex, vestibulospinal
reflex, and c-Fos protein expression in the medial
vestibular nucleus were measured following left labyrinthectomy.
Spontaneous nystagmus, head deviation, and flexion of
lesion sided limbs occurred after labyrinthectomy.
However, electrical stimulation to the lesioned
vestibular system abolished spontaneous nystagmus and
roll head tilt, and restored walking movement as well as eye movement induced
by sinusoidal rotation. c-Fos protein expression
showed significant increase in left medial vestibular nucleus than in right
medial vestibular nucleus after 6 hours of labyrinthectomy,
but electrical stimulation reduced asymmetry of c-Fos
protein expression in the bilateral medial vestibular nucleus. These results
indicate that electrical stimulation can restore postural disturbance caused by
vestibular disorders and facilitate neuronal plasticity following injury.
Key words:
electrical stimulation, vestibular symptom, c-Fos,
neuronal plasticity
INTRODUCTION
Loss of unilateral vestibular function, as a
result of unilateral labyrinthectomy (ULX), transection of the VIII nerve, or vestibular neuritis,
causes an imbalance in resting electrical activity between the bilateral
vestibular nuclei which results in vestibular symptoms including nausea,
vomiting, vertigo, spontaneous nystagmus, head
oscillation, and head deviation. However, over a period of a few days or weeks
following ULX, some of these symptoms abate in a process of behavioral recovery
known as vestibular compensation,1)
Considering the main cause of vestibular symptom is deprivation of
afferent signals from the unilateral vestibular receptors, restoration of the
afferent signals from the lesioned vestibular
receptors may recover from the vestibular symptoms. Electrical stimulation
applied to the lesioned vestibular system may restore
the afferent signals from the lesioned vestibular
system and facilitate neuronal plasticity in the vestibular nuclei, since the
electrical stimulation has a direct effect on the vestibular system as well as
other metabolic effects.2) In
this study effects of electrical stimulation to the lesioned
vestibular system on vestibular compensation were investigated by means of
behavioral and immunohistochemical studies in
unilateral labyrinthectomized rabbits.
METHODS
Nine rabbits weighing 2.0 - 2.5 kg with intact
vestibular function were used in this study. Left labyrinthectomy
was performed in this experiment. In order to apply electrical stimulation to
the lesioned vestibular nerve, two teflon-coated stainless steel wires (0.1 mm in diameter)
were implanted in the lesioned ampullary
portion. Electrical stimulation was applied by 3 - 7 V, 1.0 ms, 100 Hz through
the electrodes which were connected to the stimulator with gyrosensor.
The stimulator turns on when the head rotates toward the lesioned
vestibular side and turns off when the head rotates toward the intact side.
Horizontal eye movement was recorded by means of a DC amplifier. Head deviation
was measured in roll head tilt which was defined as the angle of deviation
between a line passing through the center of the animal's head in the coronal
plane and gravitational vertical. In immunohistochemistry,
number of c-Fos protein expression was measured in
the vestibular nuclei by image analysis system.
RESULTS
1. Eye movement
and head deviation
Persistent spontaneous nystagmus
appeared following ULX and disappeared 4 days after. However, the nystagmus disappeared 3 days after ULX in electrical
stimulated rabbits. Sinusoidal rotation of the whole body about vertical axis
produced nystagmus, whose direction was consistent
with the direction of rotation and the velocity was symmetrical by rotation on
either side. However just after ULX, spontaneous nystagmus
occurred only on sinusoidal rotation and the fast component of nystagmus was directed toward the intact labyrinthine side,
even though the rotation imposed was toward the lesioned
side. The direction of eye movement induced by sinusoidal rotation at 0.1 Hz
did not show a normal pattern of the vestibuloocular
reflex until 4 days after labyrinthectomy.
Directional preponderance representing the symmetry of bilateral vestibular
function was more than 100% until 4 days after ULX, which means severe
asymmetry of bilateral vestibular functions. Electrical stimulation to the lesioned vestibular system during sinusoidal rotation
following ULX produced the normal pattern of vestibuloocular
reflex, even on rotation toward the lesioned side. In
addition to the eye movement by rotation, spontaneous nystagmus
and head deviation were abolished, and the rabbit could move just the same as
an intact animal during electrical stimulation. Degree of roll head tilt was
reduced by electrical stimulation (Fig. 1).
Fig. 1. Effect of electrical stimulation on vestibuloocular reflex induced by sinusoidal rotation of
the whole body in a left labyrinthectomized rabbit.
CON, right-beating nystagmus by rightward rotation
and left-beating nystagmus by leftward rotation in
intact labyrinth; ULX, right-beating nystagmus by
right- or leftward rotation following left ULX; ULX+ES, normal pattern of eye
movement was restored by electrical stimulation of left vestibular system; P,
position curve of rotation; F, fast component of nystagmus;
S, slow component.
2. Expression of
c-Fos protein
In rabbits without
ULX, few of c-Fos protein neurons appeared in some
brain stem nuclei including MVN and inferior olivary
nuclei. Compared to labyrinthine intact rabbits, ULX produced marked induction
of c-Fos protein neurons in the bilateral MVN, prepositus hypoglossi, and beta
nuclei of inferior olivary nuclei 2 hours after ULX.
This induction was asymmetrical in that the number of c-Fos
protein neurons contralateral MVN were much higher
than ipsilateral MVN to the lesioned
side (p<0.05). Six hours after ULX, there was a significant reduction of c-Fos protein neurons in contralateral
MVN than that in ipsilateral MVN so that the number
of c-Fos protein neurons was slightly higher in ipsilateral MVN than contralateral
MVN. Asymmetric c-Fos protein expression between ipsilateral MVN and contralateral
MVN was also observed up to 24 hours after ULX and disappeared 72 hours after
ULX. However, electrical stimulation after ULX reduced asymmetry in c-Fos protein expression. Number of c-Fos
protein neurons was higher in contralateral MVN than ipsilateral one 2 hours after ULX and higher in ipsilateral MVN than contralateral
one 6 hours after ULX, but there was no significant difference between the
bilateral MVN 12 hours after ULX 
(Fig. 2).
POST-OP 12
Hrs POST-OP 2
Hrs
Fig. 2. Effect of electrical stimulation on c-Fos protin expression in medial vestibular nuclei (MVN)
following ULX. ULX, unilateral labyrinthectomy;
ULX+ES, unilateral labyrinthectomy with electrical
stimulation; INTACT, MVN in intact labyrinthine side; LESION, MVN in lesioned labyrinthine side. *compared with INTACT (*p<0.05, **p<0.01).
DISCUSSION
Asymmetry of electrical activity in the bilateral vestibular nuclei is considered as a main cause of vestibular symptoms resulting from loss of unilateral vestibular function. Electrical activity in ipsilateral vestibular nuclei to the lesioned side is suppressed by commissural connections and deprivation of afferent signals since ULX deprives peripheral receptors of their afferent signals. This asymmetry of electrical activity after ULX has the same effect as excitation of contralateral vestibular system and inhibition of ipsilateral vestibular system. The direction of spontaneous nystagmus and head deviation after ULX was corresponded to the response induced by electrical stimulation of contralateral vestibular system. c-Fos protein, one of the immediate early gene products, can be expressed by a variety of stimuli in neurons of CNS, considers as a useful marker for detecting changes in neuronal activity.3) Recent studies have shown the induction of c-Fos protein in the vestibular nuclei in response to otolith stimulation, ULX, or vestibulocerebellectomy.4 - 7) Considering that the induction of c-Fos protein expression in neurons occurred within 20 minutes by transsynaptic depolarization 3) a lot of c-Fos protein neurons in the bilateral MVN 2 hours after ULX may result from transsynaptic excitation of CNS connecting with vestibular nuclei. And reduction of c-Fos protein neurons in contralateral MVN may be caused by inhibitory synaptic input from vestibulocerebellum and long term depression within contralateral MVN itself.
Electrical stimulation of the lesioned
side vestibular system activates the ipsilateral
vestibular nuclei which was suppressed by labyrinthectomy,
and inhibits contralateral
vestibular nuclei by way of the inhibitory interneuron
from the ipsilateral
side.8) Disappearance of ULX
induced- spontaneous nystagmus
and head deviation during electrical stimulation suggests that electrical
stimulation has a very potent effect on acute vestibular symptoms caused by
loss of peripheral vestibular system.9) Electrical stimulation
reduced asymmetry in c-Fos
protein expression of the bilateral MVN
after ULX. This immunohistochemical
result also suggests that electrical stimulation facilitates vestibular
compensation. Underlying mechanism of electrical stimulation on vestibular
compensation could have several explanations, such as unmasking of existing
connections, functioning blind axonal endings, supersensitivity
and up-regulation of receptors for neurotransmitters
in vestibular nuclei. In summary, electrical stimulation to the lesioned vestibular
system after ULX facilitated recovery of acute
vestibular symptoms as well as neuronal plasticity by activation of the lesioned vestibular
nuclei, vestibulocerebellum
or other CNS.
(Supported by Braintech 97-N1-02-03-A-01)
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