Feasibility and Safety of Vagal Stimulation In Monkey Model

Abstract

The feasibility, safety, and preliminary effects of chronic vagal stimulation were studied in an aluminagel monkey model. Pilot studies to perfect the equipment, determine stimulation thresholds, and insure the comfort and safety of the animals preceded this study. Four monkeys were equipped with an indwelling, 2-electrode cuff (titanium bands spaced 7 mm apart; silicone encased; 1.5 cm total length) in contact around the right vagus nerve; avoidance of the cardiac branch was confirmed by electrocardiograms. After postsurgical recovery, the intact and awake animals received constant-current stimulation (5 mA; 83 Hz, 143 Hz, or 50-250 Hz randomly; 0.5-ms pulse width) at the onset of every spontaneous seizure for the duration of the seizure or every 3 h for 40 s if stimulation had not occurred in the preceding hour. Stimulation periods of 2-6 weeks, with differing levels of stimulation, were preceded and followed by at least a 2-week baseline period of no stimulation. During the stimulation periods, the seizure rate decreased to zero in two monkeys and the interseizure intervals became invariable in the remaining two monkeys. These effects carried over temporarily into the poststimulation baseline periods. Vagal stimulation had no consistent effects on seizure severity or EEG interictal spikes. Histological studies of six vagus nerves were unable to separate electrode cuff damage from any direct effects stimulation may have had on the nerves. Although it appears that chronic vagal stimulation is feasible and that epileptogenic processes are influenced, the safety and efficacy of the procedure are still in question.

Vagus nerve stimulation to augment recovery from severe traumatic brain injury impeding consciousness: a prospective pilot clinical trial

“…16 Fifty years later neurophysiologist Jacob Zabara developed his vagal nerve stimulator that reduced strychnine-induced seizures in dogs 17 . His work was duplicated in other species including monkeys 18 and rats. 19,20 Pilot studies with the human VNS for epilepsy began in November 1988.…”

Vagus Nerve Prolonged Stimulation in Cats: Effects on Epileptogenesis (Amygdala Electrical Kindling): Behavioral and Electrographic Changes

“…Low-voltage electric vagus nerve stimulation (VNS) reduces seizures induced by the systemic application of pentylenetetrazol (17), penicillin (18), and electroshock in rodents (19), as well as the spikes of a strychninic focus (20) and generalized seizures induced by strychnine in canines (21). In primates, seizures induced by the topical application of alumina gel also were inhibited (22). This study evaluated the effect of prolonged VNS on cats' behavioral and electrographic changes induced by daily electrical stimulation of the amygdala.…”

Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS)

“…VNS also has effects on sleep and arousal states. VNS decreases daytime sleepiness in humans (Malow et al, 2001) and promotes increased attention and arousal in animals (Lockard et al, 1990). These findings suggest that VNS may be a potent modulator of cognition through influences on ascending arousal systems.…”