Moving Towards Preconditioning for Neurological Disorders: Are We Ready for Clinical Trials?

The large volume of preclinical investigations begets the question of whether to proceed with clinical trials in preconditioning for neurological disorders, particularly for treatment of human cerebral ischemia. This important question was discussed during the 2nd Translational Preconditioning Meeting held at the University of Miami. While recommendations for proceeding to clinical trials have been devised in other fields of stroke therapy, such as neuroprotection, no such guidelines exist for preconditioning. During the discussion, the general opinion was to proceed with clinical preconditioning trials, with the understanding that initial trials be exploratory in nature and focus on the development of biomarkers, assessing the elicitability of the preconditioning response

Delta opioid receptors and cardioprotection

The opioid receptor family, with associated endogenous ligands, has numerous roles throughout the body. Moreover, the delta opioid receptor (DORs) has various integrated roles within the physiological systems, including the cardiovascular system. While DORs are important modulators of cardiovascular autonomic balance, they are well-established contributors to cardioprotective mechanisms. Both endogenous and exogenous opioids acting upon DORs have roles in myocardial hibernation and protection against ischaemia-reperfusion (I-R) injury. Downstream signalling mechanisms governing protective responses alternate, depending on the timing and duration of DOR activation. The following review describes models and mechanisms of DOR-mediated cardioprotection, the impact of co-morbidities and challenges for clinical translation