The Parasympathetic Nervous System in the Quest for Stroke Therapeutics

Cheyuo, Cletus; Jacob, Asha; Wu, Rongqian; Zhou, Mian; Coppa, Gene F.; Wang, Haichao

doi:10.1038/jcbfm.2011.24

Cited by 89 publications

(59 citation statements)

References 87 publications

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“…The concept that parasympathetic stimulation has an antioxidant effect is well known and supported by many findings in experimental 21–25 and clinical cardiovascular research, related to heart failure 21, 26, 27 and stroke 28, 29 .…”

Section: Discussionmentioning

confidence: 86%

Oxygen-induced impairment in arterial function is corrected by slow breathing in patients with type 1 diabetes

Bernardi

Gordin

Bordino

et al. 2017

Sci Rep

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Hyperoxia and slow breathing acutely improve autonomic function in type-1 diabetes. However, their effects on arterial function may reveal different mechanisms, perhaps potentially useful. To test the effects of oxygen and slow breathing we measured arterial function (augmentation index, pulse wave velocity), baroreflex sensitivity (BRS) and oxygen saturation (SAT), during spontaneous and slow breathing (6 breaths/min), in normoxia and hyperoxia (5 L/min oxygen) in 91 type-1 diabetic and 40 age-matched control participants. During normoxic spontaneous breathing diabetic subjects had lower BRS and SAT, and worse arterial function. Hyperoxia and slow breathing increased BRS and SAT. Hyperoxia increased blood pressure and worsened arterial function. Slow breathing improved arterial function and diastolic blood pressure. Combined administration prevented the hyperoxia-induced arterial pressure and function worsening. Control subjects showed a similar pattern, but with lesser or no statistical significance. Oxygen-driven autonomic improvement could depend on transient arterial stiffening and hypertension (well-known irritative effect of free-radicals on endothelium), inducing reflex increase in BRS. Slow breathing-induced improvement in BRS may result from improved SAT, reduced sympathetic activity and improved vascular function, and/or parasympathetic-driven antioxidant effect. Lower oxidative stress could explain blunted effects in controls. Slow breathing could be a simple beneficial intervention in diabetes.

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Section: Discussionmentioning

confidence: 86%

Oxygen-induced impairment in arterial function is corrected by slow breathing in patients with type 1 diabetes

Bernardi

Gordin

Bordino

et al. 2017

Sci Rep

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“…Eighty percent of the vagus nerve is comprised of sensory afferents, which terminate in the NTS bilaterally, and then project to the LC, DRN, nucleus basalis and cerebellar fastigial nucleus among other structures [18; 19]. VNS upregulates c-fos expression in the NTS and the LC [4; 21], and increases neuronal firing in the LC [22; 32] and the DRN [22].…”

Section: Discussionmentioning

confidence: 99%

Vagus nerve stimulation inhibits cortical spreading depression

Chen

Morais

et al. 2016

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141

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Vagus nerve stimulation has recently been reported to improve symptoms of migraine. Cortical spreading depression is the electrophysiological event underlying migraine aura, and a trigger for headache. We tested whether vagus nerve stimulation inhibits cortical spreading depression to explain its anti-migraine effect. Vagus nerve stimulation was delivered either non-invasively through the skin or directly by electrodes placed around the vagus nerve unilaterally. Systemic physiology was monitored throughout the study. Both non-invasive transcutaneous and invasive direct vagus nerve stimulation significantly suppressed spreading depression susceptibility in the occipital cortex in rats. The electrical stimulation threshold to evoke a spreading depression was elevated by more than two-fold, the frequency of spreading depressions during continuous topical 1M KCl was reduced by ~40%, and propagation speed of spreading depression was reduced by ~15%. This effect developed within 30 minutes after vagus nerve stimulation. Non-invasive transcutaneous vagus nerve stimulation was as efficacious as direct invasive vagus nerve stimulation, and the efficacy did not differ between the ipsilateral and contralateral hemispheres. Our findings provide a potential mechanism by which vagus nerve stimulation may be efficacious in migraine, and suggest that susceptibility to spreading depression is a suitable platform to optimize its efficacy.

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“…nVNS leads to inhibition of MCAO-induced immune response in the brain: cVNS causes marked inhibition of the immune response to various stimuli both in the periphery and the central nervous system [12, 14]. We explored whether nVNS was able to inhibit microglia activation and normalize altered cytokine levels after MCAO.…”

Section: Methodsmentioning

confidence: 99%

“…Unlike intracranial structures that require craniotomy for access, the vagus nerve is accessible in the neck and hence can be stimulated using surgically implanted electrodes following a small incision in the overlying skin. Neural impulses following cervical vagus nerve stimulation (cVNS) project to a wide variety of cortical and subcortical structures via the nucleus tractus solitarius (NTS)[9, 10] and can activate circuits that inhibit neuronal excitability [11] and block microglial response to ischemia-induced inflammation [12]. …”

Section: Introductionmentioning

confidence: 99%

Transcutaneous Cervical Vagus Nerve Stimulation Ameliorates Acute Ischemic Injury in Rats

Nasser

Simon³

et al. 2016

Brain Stimulation

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Background Direct stimulation of the vagus nerve in the neck via surgically implanted electrodes is protective in animal models of stroke. We sought to determine the safety and efficacy of a non-invasive cervical VNS (nVNS) method using surface electrodes applied to the skin overlying the vagus nerve in the neck in a model of middle cerebral artery occlusion (MCAO). Methods nVNS was initiated variable times after MCAO hour in rats (n=33). Control animals received sham stimulation (n=33). Infarct volume and functional outcome were assessed on day 7. Brains were processed by immunohistochemistry for microglial activation and cytokine levels. The ability of nVNS to activate the nucleus tractus solitarius (NTS) was assessed using c-Fos immunohistochemistry. Results Infarct volume was 43.15±3.36 percent of the contralateral hemisphere (PCH) in control and 28.75±4.22 PCH in nVNS-treated animals (p<0.05). The effect of nVNS on infarct size was consistent when stimulation was initiated up to 4 hours after MCAO. There was no difference in heart rate and blood pressure between control and nVNS-treated animals. The number of c-Fos positive cells was 32.4±10.6 and 6.2±6.3 in the ipsilateral NTS (p<0.05) and 30.4±11.2 and 5.8±4.3 in the contralateral NTS (p<0.05) in nVNS-treated and control animals, respectively. nVNS reduced the number of Iba-1, CD68, and TNF-α positive cells and increased the number of HMGB1 positive cells. Conclusions nVNS inhibits ischemia-induced immune activation and reduces the extent of tissue injury and functional deficit in rats without causing cardiac or hemodynamic adverse effects when initiated up to 4 hours after MCAO.

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The Parasympathetic Nervous System in the Quest for Stroke Therapeutics

Cited by 89 publications

References 87 publications

Oxygen-induced impairment in arterial function is corrected by slow breathing in patients with type 1 diabetes

Oxygen-induced impairment in arterial function is corrected by slow breathing in patients with type 1 diabetes

Vagus nerve stimulation inhibits cortical spreading depression

Transcutaneous Cervical Vagus Nerve Stimulation Ameliorates Acute Ischemic Injury in Rats

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