Translational Stroke Research Using a Rabbit Embolic Stroke Model: A Correlative Analysis Hypothesis for Novel Therapy Development

Alteplase (tissue plasminogen activator, tPA) is currently the only FDA-approved treatment that can be given to acute ischemic stroke (AIS) patients if patients present within 3 h of an ischemic stroke. After 14 years of alteplase clinical research, evidence now suggests that the therapeutic treatment window can be expanded 4.5 h, but this is not formally approved by the FDA. Even though there remains a significant risk of intracerebral hemorrhage associated with alteplase administration, there is an increased chance of favorable outcome with tPA treatment. Over the last 30 years, the use of preclinical models has assisted with the search for new effective treatments for stroke, but there has been difficulty with the translation of efficacy from animals to humans. Current research focuses on the development of new and potentially useful thrombolytics, neuroprotective agents, and devices which are also being tested for efficacy in preclinical and clinical trials. One model in particular, the rabbit small clot embolic stroke model (RSCEM) which was developed to test tPA for efficacy, remains the only preclinical model used to gain FDA approval of a therapeutic for stroke. Correlative analyses from existing preclinical translational studies and clinical trials indicate that there is a therapeutic window ratio (ARR) of 2.43-3 between the RSCEM and AIS patients. In conclusion, the RSCEM can be used as an effective translational tool to gauge the clinical potential of new treatments

Disorders of consciousness

peer reviewedDisorders of consciousness (DOC) place numerous challenges to healthcare professionals and clinical investigators, as they involve a variety of pathophysiological mechanisms, which are not yet clearly understood. Research studies have been conducted for promoting a better comprehension on these neurological conditions and making progress on diagnostic and therapeutic approaches. This book chapter presents information collected in a review of the 70 most cited clinical trials in DOC. This review was conducted by using the online database “Web of Science” searching for articles published between 1995 and 2015. Essential methodology and design aspects of these reviewed studies, based on the CONSORT guidelines, are deeply discussed in this chapter with a view to improve the conduction of clinical trials on disorders of consciousness and provide recommendations for advancing the field. © Springer Science+Business Media, LLC, part of Springer Nature 2018