| Vagus nerve stimulation (VNS) has been proposed as a novel non-drug anticonvulsant approach to treat patients with refractory epilepsy in the end of 1980's. The effective, safe, tolerable and feasible characteristics made it another choice for many intractable seizure patients before the surgery treatment.Although researches dating back to 1930's present numerous evidence of the wide spread physiological effects and mechanisms for vagus nerve stimulation, together with prospective and retrospective current clinical data analyses on various patients, the detailed mechanisms are not fully understood. The widely accepted hypotheses suggest that: the nucleus of the solitary tract (NTS) is the most important structure in mediating effects of the VNS. The afferent electric stimulation conveyed mainly by the C type unmyelinated fibers in the vagus nerve stem terminate in the NTS, which then project to extensive brainstem reticular formation, subcortical structures and probably change the activities of the neurons in these regions, and in turn change the seizure susceptibility. The levels of many neurotransmitters, including excitatory and inhibitory appeared to change following the VNS.Astrocytes (ASs) constitute nearly half of the total central nervous system(CNS) and as research progresses, an increasingly important role of the ASs hasbeen revealed. Much evidence has shown that the ASs are similar to neurons in many aspects: they respond to neurotransmitters, integrate inputs from neurons and other ASs, signal over a long range and modulate synaptic activity. There are probably some important communication and material exchange between them. Now, ASs have come to the center stage in our efforts to understand the function of the brain.In our study, we try to demonstrate the mechanisms for the anticonvulsive effect of the VNS from two aspects. First, we investigated the expression of an immediate early gene, Fos protein, combined with the HRP retrograde tracing technique to reveal the projection pathways. We also used electroencephalography to identify the inhibitory function of deep brain structures. Second, we used immunohistochemical methods to double and triple stain the preparation and used immonoelectromicroscopy to observe the expression and distribution of Fos and GFAP, a specific marker for astrocytes in the medullary visceral zone (MVZ), the hippocampal formation, cerebral cortexes and other areas related to VNS after the complex partial seizures were induced by KA. Our results shown:1. The VNS induced a significant increase in Fos immunoreactivity in the bilateral nucleus of solitary tract, the locus coeruleus, the parabrachial nucleus, the periaqueductal gray of midbrain, the lateral habenular nucleus, the paraventricular thalamic nucleus, the paraventricular hypothalamic nucleus. Dense Fos-immunoreactive staining was also seen in the central nucleus of amygdala, the bed nucleus of stria terminalis, the lateral septal nucleus and the prepiriform cortex.2. When trace retrogradely, WGA-HRP was microinjected into the centralamygdaloid nucleus or the ventral hippocampus respectively using the stereotaxic method, HRP/Fos/TH triple labeled neurons could be found in the MVZ in the Ce injection group, whereas HRP/Fos double stained neurons appeared in the septum and the periventricular (PV) hypothalamic nucleus.3. After VNS pretreament, the frequency of the generalized tonic clonic seizures significantly decreased; the initial latency of ictal obviously delayed; the mean duration of seizures reduced. VNS can also inhibit the abnormal discharge of amygdala nucleus significantly.4. The distribution of Fos like positive neurons was fundamentally similar to the pattern of GFAP positive cells in the MVZ after KA injection. The expression of GFAP began to increase 15min after seizure induction, and reached maximum at Ih; while Fos positive neurons began to appear at 30min, and peaked at 2h. Some double-labeled neurons of Fos and TH were encapsuled by concentrated GFAP positive...
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