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 that might foster brain repair could be acutely deleterious or neurotoxic and vice versa, making the timing of treatment administration after
stroke critical. Therefore, in our efforts to discover a new
stroke therapy, we decided to focus on identifying brain repair elements that were (1) endogenously and actively generated in response to
stroke in both human and experimental animal brains, (2) present acutely and chronically after
ischemic stroke, suggesting that they could have a role in acute neuroprotection and chronic neurorepair, and (3) able to be administered peripherally and reach the site of
stroke brain injury. In this review, I will discuss the evidence that suggests that
perlecan domain V may be just that substance, a potential beacon of hope for
stroke patients.