Clinical studies and anti‐inflammatory mechanisms of treatments

Abstract

Summary In this exciting era, we are coming closer and closer to bringing an anti-inflammatory therapy to the clinic for the purpose of seizure prevention, modification, and/or suppression. At present, it is unclear what this approach might entail, and what form it will take. Irrespective of the therapy that ultimately reaches the clinic, there will be some commonalities with regard to clinical trials. A number of animal models have now been used to identify inflammation as a major underlying mechanism of both chronic seizures and the epileptogenic process. These models have demonstrated that specific anti-inflammatory treatments can be effective at both suppressing chronic seizures and interfering with the process of epileptogenesis. Some of these have already been evaluated in early phase clinical trials. It can be expected that there will soon be more clinical trials of both “conventional, broad spectrum” anti-inflammatory agents and novel new approaches to utilizing specific anti-inflammatory therapies with drugs or other therapeutic interventions. A summary of some of those approaches appears below, as well as a discussion of the issues facing clinical trials in this new domain.

Non-invasive Auricular Vagus Nerve Stimulation as a Potential Treatment for Covid19-Originated Acute Respiratory Distress Syndrome

“…aVNS effects are systemic: the auricular branch of the vagus nerve projects directly to the NST and through that it excites DMNV neurons that modulate the parasympathetic division of the autonomic nervous system ( Figure 1 ), an in particular the cardiovascular, respiratory and immunological processes. aVNS therapeutic effects (Kaniusas et al, 2019a , b ) in inflammation, respiratory dysfunction and cardiovascular diseases include reduction of pro-inflammatory cytokines (Tracey, 2007 ; Stavrakis et al, 2015 ), decrease of inflammation level in chronic inflammatory processes like rheumatoid arthritis, postoperative ileus, inflammatory bowel disease (Crohn's disease, ulcerative colitis), systemic inflammation and attenuation of the acute postsurgical inflammatory response after lung lobectomy (Barone et al, 2007 ; Bernateck et al, 2008 ; Chakravarthy et al, 2015 ; Kox et al, 2015 ; Marshall et al, 2015 ; Bonaz et al, 2016 ; Koopman et al, 2016 ; Kwan et al, 2016 ; French et al, 2017 ; Hoover, 2017 ; Salama et al, 2017 ). aVNS resulted in an increase of the middle cerebral and supratrochlear artery blood flow velocity in human subjects (Széles and Litscher, 2004 ) and a decrease of the velocity of the carotid-femoral flow (Hackl et al, 2017 ).…”

Cannabidiol effects on behaviour and immune gene expression in zebrafish (Danio rerio)

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Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options

“…Finally, broad spectrum imunosuppressive and antiinflammatory steroids, diet-based treatments such as the ketogenic diet, and neurostimulation such as the vagal nerve stimulation may control drug-resistant seizures in a proportion of epilepsy patients, particularly in the pediatric population (French et al, 2017). These therapeutic approaches are endowed of antiinflammatory effects, and steroids also repair BBB dysfunction and vessel inflammation by reducing the brain extravasation of leukocytes.…”