Neuromodulation : journal of the International Neuromodulation Society
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We consider two consequences of brain capillary ultrastructure in neuromodulation. First, blood-brain barrier (BBB) polarization as a consequence of current crossing between interstitial space and the blood. Second, interstitial current flow distortion around capillaries impacting neuronal stimulation. ⋯ BBB stimulation by principle 1 suggests novel therapeutic strategies such as boosting metabolic capacity or interstitial fluid clearance. Whereas the spatial profile of EBRAIN is traditionally assumed to depend only on macroscopic anatomy, principle 2 suggests a central role for local capillary ultrastructure-which impact forms of neuromodulation including deep brain stimulation (DBS), spinal cord stimulation (SCS), transcranial magnetic stimulation (TMS), electroconvulsive therapy (ECT), and transcranial electrical stimulation (tES)/transcranial direct current stimulation (tDCS).
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Multiple sclerosis (MS) is often associated with urological disorders, mainly urinary incontinence and retention, the management of which being necessary to improve patient's quality of life (QOL) and to reduce potential urological complications. Besides the classical treatments based mainly on anticholinergics and/or self-catheterization, several neuromodulation techniques have been tried in recent years to improve these urinary disorders. By this review, we aim at providing an overview of neuromodulation and electrostimulation approaches to manage urinary symptoms in MS patients. ⋯ PTNS and SNM seem to be effective and safe therapeutic options for treating lower urinary tract symptoms in MS patients principally in case of overactive bladder (OAB) symptoms. Similarly, also SCS and TMS have been shown to be effective, despite the very limited number of patients and the small number of studies found in the literature. Interestingly, these techniques are effective even in patients who do not respond well to conservative therapies, such as anticholinergics. Furthermore, given their safety and efficacy, stimulations such as PTNS could be considered as a first-line treatment for OAB in MS patients, also considering that they are often preferred by patients to other commonly used treatments.
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Review
Synaptic Plasticity 101: The Story of the AMPA Receptor for the Brain Stimulation Practitioner.
The fields of Neurobiology and Neuromodulation have never been closer. Consequently, the phrase "synaptic plasticity" has become very familiar to non-basic scientists, without actually being very familiar. We present the "Story of the AMPA receptor," an easy-to-understand "10,000 ft" narrative overview of synaptic plasticity, oriented toward the brain stimulation clinician or scientist without basic science training. ⋯ More specifically, AMPA receptor delivery to (LTP induction), removal from (LTD), or recycling within (LTP maintenance) the synapse is determined by the status of phosphorylation and protein binding at specific sites on the tails of AMPA receptor subunits: GluA1 and GluA2. Finally, we relate these to transcranial magnetic stimulation (TMS) treatment, highlighting evidences for LTP as the basis of high-frequency TMS therapy, and briefly touch on the role of plasticity for other brain stimulation modalities. In summary, we present Synaptic Plasticity 101 as a singular introductory reference for those less familiar with the mechanisms of synaptic plasticity.
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Aneurysmal subarachnoid hemorrhage (SAH) continues to be a difficult cerebrovascular disease with limited pharmacologic treatment options. Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are leading causes of morbidity and mortality after SAH. Despite the advances in the understanding of its pathophysiology and tremendous efforts to date, nimodipine is currently the sole Food and Drug Administration-approved treatment for patients with SAH, with benefits that are marginal at best. The neuromodulation therapies are promising, especially those that target CV and DCI to improve functional outcomes. The aim of this review is therefore to summarize the available evidence for each type of neuromodulation for CV and DCI, with a special focus on its pathophysiological mechanisms, in addition to their clinical utility and drawbacks, which we hope will lead to future translational therapy options after SAH. ⋯ DCI has a complex pathogenesis, making the unique anatomical distribution and pleiotropic capabilities of various types of neuromodulation a promising field of study. We may be at the cusp of a breakthrough in the use of these techniques for the treatment of this stubbornly difficult disease.
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Acute cerebral ischemia is characterized by several pathological processes evolving during time, which contribute to the final tissue damage. Secondary processes, such as prolonged inflammatory response, impaired mitochondrial function, and oxidative stress, are responsible for the progression of brain injury to the peri-infarct area, called "penumbra." Adenosine has been shown to play a crucial role in regulating the inflammatory cascade following brain ischemia. Pulsed electromagnetic fields (PEMFs) act as modulators of adenosine receptors, increasing the functionality of the endogenous adenosine. In particular, PEMF exposure induces a significant upregulation of A2A and A3 adenosine receptors in different neuronal cell types. Several lines of evidence suggest that PEMF exposure might play a neuroprotective role after ischemic damage. ⋯ Altogether, these data demonstrate the efficacy of PEMFs against several mechanisms underlying ischemic damage and suggest that PEMFs might represent a novel noninvasive adjunctive treatment for acute ischemic stroke, providing neuroprotection and reducing functional deficits following ischemia.