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Noninvasive Vagus Nerve Stimulation Prevents Ruptures and Improves Outcomes in a Model of Intracranial Aneurysm in Mice.
- Source :
-
Stroke [Stroke] 2019 May; Vol. 50 (5), pp. 1216-1223. - Publication Year :
- 2019
-
Abstract
- Background and Purpose- Inflammation is a critical determinant of aneurysmal wall destabilization, growth, and rupture risk. Targeting inflammation may suppress aneurysm rupture. Vagus nerve stimulation (VNS) has been shown to suppress inflammation both systemically and in the central nervous system. Therefore, we tested the effect of a novel noninvasive transcutaneous VNS approach on aneurysm rupture and outcome in a mouse model of intracranial aneurysm formation with wall inflammation. Methods- Aneurysms were induced by a single stereotaxic injection of elastase into the cerebrospinal fluid at the skull base, combined with systemic deoxycorticosterone-salt hypertension, without or with high-salt diet, for mild or severe outcomes, respectively. Cervical VNS (two 2-minute stimulations 5 minutes apart) was delivered once a day starting from the day after elastase injection for the duration of follow-up. Transcutaneous stimulation of the femoral nerve (FNS) served as control. Multiple aneurysms developed in the circle of Willis and its major branches, resulting in spontaneous ruptures and subarachnoid hemorrhage, neurological deficits, and mortality. Results- In the milder model, VNS significantly reduced aneurysm rupture rate compared with FNS (29% versus 80%, respectively). Subarachnoid hemorrhage grades were also lower in the VNS group. In the more severe model, both VNS and FNS arms developed very high rupture rates (77% and 85%, respectively). However, VNS significantly improved the survival rate compared with FNS after rupture (median survival 13 versus 6 days, respectively), without diminishing the subarachnoid hemorrhage grades. Chronic daily VNS reduced MMP-9 (matrix metalloproteinase-9) expression compared with FNS, providing a potential mechanism of action. As an important control, chronic daily VNS did not alter systemic arterial blood pressure compared with FNS. Conclusions- VNS can reduce aneurysm rupture rates and improve the outcome from ruptured aneurysms.
- Subjects :
- Aneurysm, Ruptured etiology
Aneurysm, Ruptured pathology
Animals
Intracranial Aneurysm etiology
Intracranial Aneurysm pathology
Male
Mice
Mice, Inbred C57BL
Pancreatic Elastase toxicity
Random Allocation
Sodium Chloride, Dietary toxicity
Swine
Treatment Outcome
Aneurysm, Ruptured prevention & control
Disease Models, Animal
Intracranial Aneurysm therapy
Vagus Nerve Stimulation methods
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4628
- Volume :
- 50
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Stroke
- Publication Type :
- Academic Journal
- Accession number :
- 30943885
- Full Text :
- https://doi.org/10.1161/STROKEAHA.118.023928