The journal Neuropharmacology recently published a new review of the current state of the art in neuroprotection for ischemic stroke. A strict definition of a neuroprotectant excludes agents that have as their goal circulatory patency or the reversal of vascular occlusion, such as thrombolytics and anticoagulants. As a consequence, the only medication that is approved for (ischemic) stroke patients, tPA, is not a neuroprotectant. Despite the explosion of interest and research in the field (as documented in Ginsberg’s review), no single neuroprotective agent has successfully survived human clinical trials. The author discusses a number of reasons why encouraging results fail to translate into human success and stresses the fact that most agents in clinical trials are administered too late to confer positive benefits, and even states that “there is practically no evidence that neuroprotection for acute ischemic stroke is possible with any agent beyond ~6h.” It is no surprise, then, that the author does not report many promising neuroprotective strategies except for therapeutic hypothermia, high-dose human albumin therapy, and hyperacute magnesium therapy.
What does this mean for cryonics? As discussed in this review about medications in human cryopreservation stabilization, neuroprotection in cryonics has never been approached as a quest to find one single “magic bullet” to protect the brain after cardiac arrest. Cryonics stabilization medications protocol consists of a number of agents that intervene at different points in the ischemic cascade, reverse and inhibit blood clotting, and improve circulation. If rapid stabilization is possible, the time-window for treatment in cryonics is usually excellent in comparison to (focal) ischemic stroke where treatment within 1-2 hours is considered “hyperacute.” But cardiac arrest after an (often) long terminal and agonal period is not equivalent to (focal) ischemic stroke, and evidence that the medications that are given to cryonics patients are of great benefit is confined to a series of (non-published) experiments on (young) healthy animals in cryonics-associated laboratories.
When the author discusses future directions to find successful neuroprotective agents, he highlights the challenge of finding funding for neuroprotective trials that include metabolic treatment and combinations of (non-proprietary) drugs. In light of the predictable failure of mono-agents that the author reports, the discussion of the potential of combination treatment is remarkably brief and confined to the point that potential neuroprotectants need to be validated in combination with thrombolytic treatment. There is now an accumulating number of research papers on combination treatment in animal models that would warrant a more systematic analysis than the obligatory acknowledgement that combination therapy might produce better neuroprotection. Perhaps the most novel part of this new review of neuroprotective agents is the discussion of the author’s own research into high-dose human albumin therapy and the brief mention of a new paper (2007) that discusses the prospects of neuroprotective strategies that “are based on the principle that drugs should be activated by the pathological state that they are intended to inhibit.”