Perlecan Domain V Therapyfor Stroke: A Beacon of Hope?

摘要

The sad reality is that in the year 2012, people are still dying or suffering from the extreme morbidity of ischemic stroke. This tragedy is only compounded by the graveyard full of once promising new therapies. While it is indeed true that the overall mortality from stroke has declined in the United States, perhaps due to increased awareness of stroke symptoms by both the lay public and physicians, it is clear that better therapies are needed. In this regard, progress has been tremendously slowed by the simple fact that experimental models of stroke and the animals that they typically employ, rats and mice, do not adequately represent human stroke. Furthermore, the neuroprotective therapeutic approach, in which potential treatments are administered with the hope of preventing the spread of dying neurons that accompanies a stroke, typically fail for a number of reasons such as there is simply more brain matter to protect in a human than there is in a rodent! For this reason, there has been somewhat of a shift in stroke research away from neuroprotection and toward a neurorepair approach. This too may be problematic in that agents thatmight foster brain repair could be acutely deleterious or neurotoxicand vice versa, making the timing of treatment administration afterstroke critical. Therefore, in our efforts to discover a new stroketherapy, we decided to focus on identifying brain repair elementsthat were (1) endogenously and actively generated in response to strokein both human and experimental animal brains, (2) present acutelyand chronically after ischemic stroke, suggesting that they couldhave a role in acute neuroprotection and chronic neurorepair, and(3) able to be administered peripherally and reach the site of strokebrain injury. In this review, I will discuss the evidence that suggeststhat perlecan domain V may be just that substance, a potential beaconof hope for stroke patients.