Do-it-yourself brain repair following stroke

Stroke is a leading cause of long-term disability and death in the United States. A team of researchers - led by Gregory Bix, at Texas A&M College of Medicine, College Station - has identified a way to exploit one of the brain's self-repair mechanisms to protect nerve cells and enhance brain repair in rodent models of stroke. The authors suggest that this approach could provide a nontoxic treatment for stroke.

The most common form of stroke (ischemic stroke) occurs when a blood vessel that brings oxygen and nutrients to the brain becomes clogged, for example with a blood clot, causing nerve cells in the affected area to die rapidly. In their study, Bix and colleagues detected in rodent models of stroke elevated levels of domain V, a naturally occurring fragment of the molecule perlecan, suggesting it might have a natural role in repairing the brain after a stroke. When administered in these models 24 hours after stroke, perlecan domain V protected nerve cells from death and promoted blood vessel growth, a key component of brain repair. The authors therefore suggest that perlecan domain V could provide a therapy that improves stroke outcome by protecting nerve cells and enhancing brain repair.

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Ischemic stroke, a condition resulting from occlusion of brain vasculature, manifests as an ischemic core of rapid cell death, surrounded by a vulnerable penumbral region. Within the penumbra, reparative revascularization (angiogenesis) and neuronal repopulation (neurogenesis) occur in close proximity, facilitating mutually supportive neuron–endothelial cell crosstalk. Additionally, angiogenic blood vessels serve as a physical scaffold for neurons to migrate toward the ischemic core. Collectively, this neurovascular coupling represents a means of post-stroke repair ripe for therapeutic exploitation. Indeed, recent experimental therapies such as pharmaceuticals, stem cells, and growth factors have attempted to capitalize on neurovascular repair concepts to promote stroke recovery. However, pharmaceutical and growth factor therapies raise questions of potentially serious systemic side effects, drug interactions, and contra-indications. Similarly, cell-based therapies raise important safety issues, including the potential for cancerous transformation.

Additionally, many factors that prevent cell death also inhibit repair, or vice versa, depending upon when they are administered after stroke. For example, NMDA receptor antagonists and protease inhibitors are both neuroprotective and detrimental to repair. VEGF further disrupts blood-brain barrier stability, promotes brain edema, and enhances hemorrhagic transformation and brain infarct size if administered acutely, but is neuroprotective and enhances angiogenesis and neurogenesis when given chronically. Thus, there is a clear need for a stroke therapy that is both neuroprotective and promotes brain repair. This need is underscored by the fact that the one FDA-approved stroke therapy, TPA, has a narrow therapeutic window of 3–4.5 hours after ischemic stroke onset.