Electrophysiological responses to vagus nerve stimulation in rats

Vagus nerve stimulation (VNS) for refractory epilepsy requires optimization of stimulation parameters to improve outcome. Measuring electrophysiological activity from the vagus nerve in response to electrical stimulation may provide an objective tool to evaluate the effects of various stimulation parameters in an experimental set-up. Rats were implanted with a stimulation electrode around the left cervical vagus nerve. Electrophysiological recordings were performed using thin point electrodes placed on the vagus nerve 2 and 4mm rostrally to the cathode. Reference/ground electrode was placed in the wound. The vagus nerve was stimulated with a biphasic, charge-balanced pulse. Silk wire was strapped along the vagus nerve to cause reversible lesions of the nerve. VNS induced an electrophysiological response consisting of a fast and a slow component. The threshold intensity was 2490±240µA and 2067±247µA respectively. The components reached their maximum amplitude at 3875±530µA and 3000±935 µA. Mean latency, at 2mm, was 0.4±0.1ms and 2.6±0.3ms. Conduction velocity for the fast component was 25m/s. The fast component disappeared by afferent lesioning the vagus nerve. The slow component disappeared by efferent lesioning, by lesioning the recurrent laryngeal nerve and by applying Vecuronium to the larynx muscles. A short, single electrical pulse activates fast conducting afferent fibers. Also efferent fibers of the recurrent laryngeal nerve are activated resulting in contraction of larynx muscles. A far field potential was recorded on the vagus nerve. Our set-up can be used to evaluate the effect of stimulation parameters at the cervical vagus nerve in rat epilepsy models

Electrophysiological responses to vagus nerve stimulation in rats

Introduction: Vagus nerve stimulation (VNS) for refractory epilepsy requires optimization of stimulation parameters in order to improve clinical outcome. Experimental research showed that VNS exerts its effect by activating afferent, fast-conducting fibers. There is however a clear need for an objective parameter reflecting effective stimulation. We recorded electrophysiological responses to stimulation of the vagus nerve in rats. Methods: Rats were implanted with a stimulation electrode around the left cervical vagus nerve. Recordings were made using thin point electrodes placed on the vagus nerve rostral to the stimulating cathode. The vagus nerve was stimulated under anesthesia with a charge-balanced biphasic pulse (5µs/phase). Results: The electrophysiological response recorded from the vagus nerve consisted of an early and a late component, identified as respectively an afferent compound action potential (CAP) and a far field potential of the larynx motor evoked potential (LMEP). The I50% for the CAP and LMEP (respectively 1.9 ± 0.3 mA and 1.6 ± 0.1 mA) were not significantly different. Mean latency for the CAP and LMEP at 1.3 ± 0.3 mm rostral to the stimulating cathode, were 0.4 ± 0.1 ms and 2.0 ± 0.2 ms respectively. At 3.1 ± 0.6 mm rostral to the stimulating cathode, a difference in response latency was measured for the CAP. Conduction velocity was calculated to be 32.5 ± 2.5 m/s. Based on the measured distance between the cuff electrode and the laryngeal muscles, conduction velocity of the efferent action potentials leading to the LMEP was calculated to be 33.3 ± 1.3 m/s. Mean rheobase and chronaxy for the CAP were respectively 35.0 ± 5.0 µA and 40.0 ± 3.5 µs. Conclusion: Short biphasic pulses with an intensity of 1.5-2.5mA activate fast-conducting vagus nerve fibers. Our set-up can be used to evaluate the effects of different stimulation parameters at the level of the cervical vagus nerve in epilepsy models

Increased hippocampal extracellular noradrenalin concentration contributes to the anticonvulsant effect of VNS in the focal pilocarpine rat model for limbic seizures

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Is cortical excitability in rats altered after 1h of high frequency, Poisson distributed cortical stimulation?

Aims : Neurostimulation is a promising treatment for patients with refractory focal epilepsy who are not amenable to resective surgery. We have evaluated the effect of high-frequency cortical stimulation on cortical excitability in the motor cortex model (CSM). In the CSM, a ramp-shaped pulse train with increasing intensity is delivered to the motor cortex. The threshold intensity for eliciting forelimb clonus is determined through behavioural observation, and used as a measure for cortical excitability. Methods : Seven male Wistar rats were implanted with epidural electrodes over the motor cortex (AP-1mm; ML±3mm). All rats underwent 1h of sham stimulation, cortical stimulation (Poisson pulse, 130Hz, PW100µs) with an intensity of 10µA, or cortical stimulation at 100µA below the baseline threshold intensity on alternating days. The threshold intensity needed to elicit forelimb clonus was determined before (mean of 4measurements at 20min intervals) and immediately, 1h, 2h and 24h after stimulation. Results : Sham stimulation did not alter the threshold to forelimb clonus. Therapeutic stimulation with an intensity of 100µA lower than baseline threshold (mean intensity 205±22µA) significantly increased the threshold to forelimb clonus from 305±22µA (before) to 347±19 (immediately after), 339±23 (1h), 327±20 (2h) and 277±21µA (24h) after stimulation (p<0.001). When stimulated at 10µA, the threshold increased from 302±25µA to 319±15µA, 318±21µA, 319±18 µA, 321±32µA. Conclusion : High-frequency, Poisson-distributed cortical stimulation during 1h decreases cortical excitability at high intensities. This effect lasted 1h. Further studies are needed to determine whether this type of stimulation can become an effective alternative treatment for patients with focal neocortical epilepsy who are not amenable to surgery

Electrophysiological responses from vagus nerve stimulation in rats

The mechanism of action of vagus nerve stimulation (VNS) for pharmacoresistant epilepsy is unknown and the therapeutic outcome is highly variable. We investigated stimulation-induced vagus nerve electrophysiological responses in rats using various stimulation parameters. Conduction velocity, I50, rheobase and chronaxie were calculated. We identified an early and late component corresponding to an afferent compound action potential (CAP) and a remote laryngeal motor-evoked potential (LMEP), respectively. The conduction velocity (CAP: 26.2 ± 1.4 m/s; LMEP: 32.4 ± 2.4 m/s) and I50 (CAP: 2.4 ± 0.3 mA; LMEP: 1.8±0.2 mA) were significantly different for both components, the rheobase (CAP: 140±30 μA; LMEP: 110±26 μA) and chronaxie (CAP: 66±7 μs; LMEP: 73±9 μs) were not. Using a pulse of 10 μs, the CAP saturated between 4-5 mA. Our method can be used to record VNS-induced electrophysiological responses in rats and provides an objective biomarker for electrical stimulation with various parameters in an experimental set-up. Our findings are potentially useful for clinical purposes in the sense that combination of VNS and recording of vagal nerve CAPs may help clinicians to determine the individual optimal intensity required to fully activate fast-conducting afferent fibers