The therapeutic effect and mechanism of Chinese medicine Xuan-Yun-Ding on posterior circulation ischemia with vertigo in a rabbit model.

The aim of research is to unveil the mechanisms of the beneficial effects of XYD on PCIV in a rabbit model. 40 New Zealand white rabbits were randomly divided into 5 groups,including normal control group (NC), model control group (MC), low-dose of XYD group (LXYD), high-dose of XYD group (HXYD) and Yang-Xue-Qin-Nao group (YXQN). PCIV rabbit model was established by feeding high-fat diet companied with paravertebral sclerotherapy and rotation exercise. The general observation, step-down test, rheoencephalogram, blood tests, histopathological detection and the plasma concentration of the effective component of XYD were investigated. After pharmacological intervening, the step-down time, REG, PL, IPL, blood viscosity, the levels of blood lipids, CRGP were significantly improved. Moreover, the vertebral artery showed the reduced stenosis of arterial lumen and less proliferation of fibrous tissue in the arterial wall in the LXYD, HXYD and YXQN group. Based on the LC-MS detection, the blood concentrations of puerarin in the LXYD and HXYD group were significantly increased after pharmacological intervening. XYD could ameliorate the symptoms of vertigo, Qi-deficiency and blood stasis in PCIV rabbits via effectively regulating the levels of blood lipids and vasoactive substances, decreasing blood viscosity, increasing CBF and protecting vestibular function.

Long-lasting increases in intrinsic excitability triggered by inhibition.

Although experience-dependent changes in neural circuits are commonly assumed to be mediated by synaptic plasticity, modifications of intrinsic excitability may serve as a complementary mechanism. In whole-cell recordings from spontaneously firing vestibular nucleus neurons, brief periods of inhibitory synaptic stimulation or direct membrane hyperpolarization triggered long-lasting increases in spontaneous firing rates and firing responses to intracellular depolarization. These increases in excitability, termed firing rate potentiation, were induced by decreases in intracellular calcium and expressed as reductions in the sensitivity to the BK-type calcium-activated potassium channel blocker iberiotoxin. Firing rate potentiation is a novel form of cellular plasticity that could contribute to motor learning in the vestibulo-ocular reflex.

Optokinetic and vestibulo-ocular reflex adjustment by GABA antagonists.

We determined if high and low doses of anti-GABAergic drugs have opposite effects on the visuo-vestibular activity in pigmented rats and examined a possible correlation with the level of GABA in the related structures. First, the horizontal optokinetic and vestibulo-ocular reflexes of most animals were depressed by high doses of anti-GABAergic drugs (10(-3) M purified picrotoxin or 10(-6) M picrotoxin in unpurified vegetal extract). Simultaneously, a drop in GABA level in the cerebellum and posterior brainstem was detected. Second, after a subsequent injection (1 ml) of the diluted extract (10(-13) M picrotoxin), the reflexes returned to normal despite the fact that no correlation with the GABA level was found. These results demonstrate that small doses of anti-GABAergic drugs reverse the depressive effect created by large doses of these drugs on the oculomotor system, and even adjust the reflexes to the stimulation. This adjustment, without correlation with the GABA level, suggest a powerful effect of very low dose of the drug to modulate either the activity of the cerebellar inhibiting input or of the vestibular nuclei neurons or to trigger the adaptation by other neurotransmitter systems involved in the performances of the reflexes.

Effects of Ginkgo biloba extract (EGb 761) on the guinea pig vestibular system.

Previous studies have demonstrated that the administration of Ginkgo biloba extract (EGb 761) improves the compensation of the vestibular syndrome induced by transection of the VIIIth nerve. To investigate the mechanisms at play, the vestibular nuclei of alert guinea pigs were perfused with EGb 761. This perfusion always induced a stereotyped reversible postural syndrome that was the mirror image of the syndrome provoked by the unilateral lesion of the otolithical receptors. This result supports the hypothesis that EGb 761 has a direct excitatory effect on the lateral vestibular nuclei (LVN) neurons. In a second step, we quantified the horizontal vestibuloocular reflex (HVOR) of the normal guinea pig following IP injection of EGb 761. In normal guinea pig, IP administration of EGb 761 led to a reversible, dose-dependent decrease of the HVOR gain without affecting the phase of the reflex. These data help to explain the therapeutic effects of EGb 761 during vestibular syndromes and strongly suggest an impact at the neuronal level.

Plasticity mechanisms in vestibular compensation in the cat are improved by an extract of Ginkgo biloba (EGb 761).

The effects of administration of an extract of Ginkgo biloba (EGb 761) on vestibular compensation was studied in unilateral vestibular neurectomized cats. This experimental model of CNS plasticity was investigated by using behavioral tests (postural disorders compensation, locomotor balance recovery), electrophysiological (spontaneous and evoked neck muscle activity) and neurophysiological (spontaneous firing rate recovery of deafferented vestibular cells) recordings, and immunocytochemical methods (synaptic loss and synaptic reoccupation within the deafferented vestibular nuclei). In all experiments, EGb 761 was administered over 30 days at daily doses of 50 mg/kg IP. The results showed a faster recovery in the EGb-treated group of cats as compared to an untreated control group. EGb administration strongly accelerated postural and locomotor balance recovery. Concomitantly, spontaneous neck muscle activity, vestibulo-collic reflexes and spontaneous firing rate of vestibular units located on the lesioned side were restored earlier. Morphological correlates characterized by a more rapid synaptic reoccupation were found in the deafferented medial vestibular nucleus by means of immunoreactive labelling using an antibody against a synaptic vesicle-associated protein (synaptophysin), but they displayed a longer time-constant in comparison with the behavioral and neurophysiological data. These results clearly demonstrate that EGb 761 acts on recovery mechanisms considered as key processes in vestibular compensation. They suggest that this substance would possess neurotrophic and/or neuritogenic properties improving functional recovery after CNS injury.