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Vagus nerve stimulation attenuates demyelination and accelerates remyelination in a Lysolecithin-induced multiple sclerosis model
ECTRIMS Online Library. Hamlin N. Oct 27, 2017; 200835
Nicole Hamlin
Nicole Hamlin
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Abstract: P1180

Type: Poster

Abstract Category: Therapy - disease modifying - 27 Neuroprotection and Repair

Background: Despite several approved therapies for multiple sclerosis (MS), there remains a need for new treatments. Vagus nerve stimulation (VNS) activates protective neuro-immune reflexes that reduce inflammation, increase Treg populations, and is neuroprotective in the central nervous system (Immunol Rev 248(1):188). We therefore postulate that VNS may have an ameliorative effect in MS.
Objective: To explore the therapeutic effect of VNS on demyelination and remyelination in a lysolecithin (LPC)-induced MS model.
Methods: To induce a self-limited demyelinating lesion, spinal cords of female BALB/c mice were injected between T3-T5 with 1% LPC (0.5 µL at 0.25 µL/min). To study the effect of VNS on demyelination, VNS (0.75-1 mA, 250 µS pulse, 10 Hz) or sham VNS (0 mA) was performed immediately following LPC administration, and the mice were euthanized on the day of expected peak lesion volume (day 4 post-induction; J Neurocytol 24(10): 775). Spinal cord lesion volumes were quantified from luxol blue-stained, 15 µm serial sections. To study the effect of VNS on remyelination, VNS or sham VNS was performed 4 days post-induction, mice were euthanized on days 8, 14, or 21 post-induction, and nerves were processed as above. Mean lesion volumes between groups were compared by t-test.
Results: VNS inhibited demyelinated lesion progression compared to sham. On day 4 post-induction, mean lesion volume in the VNS group was significantly lower than in the sham group (VNS = 0.03 mm3 ± 0.006, n=5, vs. Sham= 0.09 mm3 ± 0.009, n=4, p = 0.0023). Remyelination occurred at a significantly accelerated rate in the VNS group. On day 8 post-induction, mean lesion volume in the VNS group was reduced to 0.02 mm3 ± 0.01, n=4. On day 14 post-induction, mean lesion volume in the VNS group was significantly lower than in the sham group (VNS = 0.0002 mm3 ± 0.007, n=12, vs. Sham= 0.03 mm3 ± 0.01, n=6, p = 0.0007). On day 14, 11/12 VNS animals had no detectable lesion. By Day 21, mean lesion volume in the sham group was 0.01 mm3 ± 0.006, n=3.
Conclusions: VNS reduced demyelination and accelerated remyelination, demonstrating a robust effect after a single dose in this model. To explore underlying mechanisms, leukocyte infiltration and oligodendrocyte recruitment are being investigated. Repeated stimulation with an implanted stimulator will be tested in experimental autoimmune encephalomyelitis to further assess the potential of VNS to treat MS.
Disclosure:
N. Hamlin is an employee of SetPoint Medical, Inc. Y.
Levine is an employee of SetPoint Medical, Inc.
Funding for this project was provided by SetPoint Medical, Inc.

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