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Advances in Molecular Research on Neuroprotective Approaches to Stroke

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 July 2024) | Viewed by 3996

Special Issue Editor


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Guest Editor
Department of Neurology, University of Göttingen Medical School, 37077 Göttingen, Germany
Interests: stroke

Special Issue Information

Dear Colleagues, 

Stroke is a leading cause of death and the most common global source of acquired physical disability. With its changing demographics, the significance of stroke and its consequences continues to grow. The current treatment options are limited to vessel recanalization, and only a small number of patients are eligible for this time-sensitive treatment. Thus, new neuroprotective approaches are urgently needed. Neuroprotection refers to interventions that preserve, restore, or regenerate the nervous system by interrupting the sequence of events triggered by ischemic stroke. Nevertheless, significant research efforts are underway to develop new neuroprotective strategies for the future. This Special Issue focuses on these novel approaches and their underlying molecular mechanisms, a comprehensive understanding of which is critical to successful bench-to-bedside translation in the future.

Dr. Matteo Haupt
Guest Editor

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Keywords

  • stroke
  • neuroprotection
  • neuroprotectants
  • neuroregeneration
  • translational research

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Published Papers (2 papers)

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Research

17 pages, 2258 KiB  
Article
Vagus Nerve Suppression in Ischemic Stroke by Carotid Artery Occlusion: Implications for Metabolic Regulation, Cognitive Function, and Gut Microbiome in a Gerbil Model
by Ting Zhang, Yu Yue, Chen Li, Xuangao Wu and Sunmin Park
Int. J. Mol. Sci. 2024, 25(14), 7831; https://doi.org/10.3390/ijms25147831 - 17 Jul 2024
Cited by 2 | Viewed by 1279
Abstract
The vagus nerve regulates metabolic homeostasis and mediates gut–brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut–brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test [...] Read more.
The vagus nerve regulates metabolic homeostasis and mediates gut–brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut–brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO_VGX), AO without VGX (AO_NVGX), no AO with VGX (NAO_VGX), and no AO without VGX (NAO_NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus. Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut–brain axis. Targeting the gut–brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke. Full article
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20 pages, 5753 KiB  
Article
Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Improves Neurological Outcome and Reduces Microglial Reactivity in a Rodent Model of Global Transient Stroke
by Amanda Moya-Gómez, Lena Pérez Font, Andreea Burlacu, Yeranddy A. Alpizar, Miriam Marañón Cardonne, Bert Brône and Annelies Bronckaers
Int. J. Mol. Sci. 2023, 24(13), 11117; https://doi.org/10.3390/ijms241311117 - 5 Jul 2023
Cited by 5 | Viewed by 2021
Abstract
Extremely low-frequency electromagnetic stimulation (ELF-EMS) was demonstrated to be significantly beneficial in rodent models of permanent stroke. The mechanism involved enhanced cerebrovascular perfusion and endothelial cell nitric oxide production. However, the possible effect on the neuroinflammatory response and its efficacy in reperfusion stroke [...] Read more.
Extremely low-frequency electromagnetic stimulation (ELF-EMS) was demonstrated to be significantly beneficial in rodent models of permanent stroke. The mechanism involved enhanced cerebrovascular perfusion and endothelial cell nitric oxide production. However, the possible effect on the neuroinflammatory response and its efficacy in reperfusion stroke models remains unclear. To evaluate ELF-EMS effectiveness and possible immunomodulatory response, we studied neurological outcome, behavior, neuronal survival, and glial reactivity in a rodent model of global transient stroke treated with 13.5 mT/60 Hz. Next, we studied microglial cells migration and, in organotypic hippocampal brain slices, we assessed neuronal survival and microglia reactivity. ELF-EMS improved the neurological score and behavior in the ischemia-reperfusion model. It also improved neuronal survival and decreased glia reactivity in the hippocampus, with microglia showing the first signs of treatment effect. In vitro ELF-EMS decreased (Lipopolysaccharide) LPS and ATP-induced microglia migration in both scratch and transwell assay. Additionally, in hippocampal brain slices, reduced microglial reactivity, improved neuronal survival, and modulation of inflammation-related markers was observed. Our study is the first to show that an EMF treatment has a direct impact on microglial migration. Furthermore, ELF-EMS has beneficial effects in an ischemia/reperfusion model, which indicates that this treatment has clinical potential as a new treatment against ischemic stroke. Full article
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