Let's be certain about sartans (and other potential new therapies for CNS injury).

Abstract

This scientific commentary refers to ‘Neurorestoration after traumatic brain injury through angiotensin II receptor blockage’, by Villapol et al. (doi:10.1093/brain/awv172). The vast majority of new drugs for the treatment of neurological injury that show efficacy in preclinical models fail in clinical trials. Accordingly, many groups instead choose to evaluate whether drugs that are already approved for other conditions can be repurposed for use in traumatic brain injury, stroke and spinal cord injury. One such group of drugs is the ‘sartans’, which are approved for the treatment of hypertension in many countries worldwide. Sartans are blockers of angiotensin II type 1 receptors (e.g. AT1R) but it should be noted that they also bind to other receptors (e.g. PPARγ peroxisome proliferator-activated receptor gamma). Two examples of sartans are candesartan and telmisartan. Sartans have demonstrable neuroprotective and anti-inflammatory properties in animal models of stroke, although evidence from human trials is inconclusive at present (Bath and Krishnan, 2014). In this issue of Brain , Villapol et al. present data indicating that candesartan and telmisartan can improve outcome after controlled cortical impact injury in mice when given acutely (up to 6 h afterwards). Genetic knockout of a receptor for sartans (AT1R) improves outcome after traumatic brain injury to a similar degree (Villapol et al. , 2015). These results might suggest therefore that sartans also warrant evaluation following brain injury in humans. The title of the paper by Villapol and co-workers refers to ‘neurorestoration’, which is a broad term that implies different mechanisms to different people. Benefits of sartans were observed up to 6 h after injury in wild-type mice, but not when given 24 h post-injury: a time frame compatible with a mechanism involving compensatory blood flow and neuroprotection. Consistent with this, both drugs did improve blood flow and reduce lesion volume …