A Review of Neuroinflammatory Mechanisms in Ischemic Stroke: Background and Therapeutic Approaches

In this review, we will discuss the relevant clinical details of acute ischemic stroke and its currently very limited therapeutic opportunities, sequentially emphasizing its populational and economical burden. Based on our increasing knowledge in molecular and cell biology of immunological mechanisms of ischemic stroke, we will introduce the main processes in the background of arterial vessel occlusion, ensuing tissue damage and following reparation. After that, we will compare the obtained results from animal models with clinical studies and thus the possible causes of foregoing failures. Following this, we will demonstrate the most important drugs tested and/or being tested in human or animal studies from the field of neuroprotection. Finally, we raise possible opportunities that can be considered in development or clinical applications of neuroprotectants

Implant for Augmentation of Cerebral Blood Flow Trial-1 (ImpACT-1). A single-arm feasibility study evaluating the safety and potential benefit of the Ischemic Stroke System for treatment of acute ischemic stroke

Background The Ischemic Stroke System is a novel device designed to deliver stimulation to the sphenopalatine ganglion(SPG).The SPG sends parasympathetic innervations to the anterior cerebral circulation. In rat stroke models, SPG stimulation results in increased cerebral blood flow, reduced infarct volume, protects the blood brain barrier, and improved neurological outcome. We present here the results of a prospective, multinational, single-arm, feasibility study designed to assess the safety, tolerability, and potential benefit of SPG stimulation inpatients with acute ischemic stroke(AIS). Methods Patients with anterior AIS, baseline NIHSS 7–20 and ability to initiate treatment within 24h from stroke onset, were implanted and treated with the SPG stimulation. Patients were followed up for 90 days. Effect was assessed by comparing the patient outcome to a matched population from the NINDS rt-PA trial placebo patients. Results Ninety-eight patients were enrolled (mean age 57years, mean baseline NIHSS 12 and mean treatment time from stroke onset 19h). The observed mortality rate(12.2%), serious adverse events (SAE)incidence(23.5%) and nature of SAE were within the expected range for the population. The modified intention to treat cohort consisted of 84 patients who were compared to matched patients from the NINDS placebo arm. Patients treated with SPG stimulation had an average mRS lower by 0.76 than the historical controls(CMH test p = 0.001). Conclusion The implantation procedure and the SPG stimulation, initiated within 24hr from stroke onset, are feasible, safe, and tolerable. The results call for a follow-up randomized trial (funded by BrainsGate; clinicaltrials.gov number, NCT03733236)

Assessment of cognitive function in female rheumatoid arthritis patients: associations with cerebrovascular pathology, depression and anxiety

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