Targeting the Brain: Neuroprotection and Neurorestoration in Ischemic Stroke

Jeffrey L. Saver, M.D., FAHA, FAAN


Pharmacotherapy. 2010;30(7):62S-69S. 

In This Article

Neuroplasticity and Brain Repair

Few areas in modern neuroscience are as rapidly evolving and rich with therapeutic promise as neurorepair and neurorehabilitation. Recent years have seen tremendous advance in our understanding of the fundamental neurobiology of neural network plasticity, axonogenesis, synaptogenesis, neuronogenesis, and other mechanisms underlying recovery of function after stroke. Promising agents already entering early-stage clinical trials include promoters of membrane repair, nerve growth factors, stem cells, laser mitochondrial bioenergetization, transcranial magnetic stimulation, and neuroprosthetics using implanted and noninvasive brain–artificial machine interfaces.[20,21]

In contrast with the long record of clinical trials of acute neuroprotection in ischemic stroke, few major trials have yet been undertaken that study pharmacologic and device interventions to promote brain repair subacutely after stroke. Many aspects of clinical trial methodology in neurorestoration are uncertain, including the best time to initiate treatment, the optimal duration of treatment, the best target patients, and the most informative and clinically relevant measures of treatment success. The most extensive clinical trial experience with brain repair enhancers has occurred somewhat inadvertently, in the course of clinical trials testing putative neuroprotective compounds. Agents that promote cell repair and cell growth, such as choline precursors and nerve growth factors, theoretically may confer both neuroprotection when administered acutely and neurorepair enhancement when given subacutely. As a result, even in the absence of well-formulated theoretical conceptions of brain repair, clinical trialists testing these compounds often administered them in both the acute and subacute period. Many of these studies can be reconceptualized as early trials of brain repair, providing greater insight into the meaning and potential clinical applicability of their findings.