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

Abstract and Introduction


Many treatments for acute ischemic stroke are vessel and blood based, but brain-based therapies also hold great promise. Acute neuroprotective therapies block the molecular elaboration of injury in hypoxic environments. Prehospital trials of magnesium sulfate are demonstrating the feasibility of delivering potentially brain-protective agents in the first minutes after stroke onset. Subacute neurorestoration therapies enhance neuroplasticity and brain reorganization after stroke. The greatest clinical experience with agents that can potentiate brain repair has been gained with choline precursors. Therapies that target the brain in patients with stroke will increasingly complement and enhance traditional vasotherapeutics.


The therapeutic armamentarium for acute ischemic stroke may be broadly divided into two categories: therapies that target the vascular system and therapies that target the nervous system. Vascular strategies include recanalization, prevention of clot propagation, and collateral enhancement. Neural strategies include acute neuroprotection and subacute promotion of brain plasticity and neurorepair. The past 2 decades have witnessed clinical breakthroughs in vascular strategies, with multiple therapies demonstrated to be of proven value (recanalization by intravenous fibrinolysis, clot propagation deterrence by aspirin) or nearly proven value (recanalization by intraarterial fibrinolysis and mechanical embolectomy). In contrast, despite ferment in basic science investigations, neuroprotection and neurorepair strategies still await translational success. Nonetheless, a vision widely shared in the stroke investigational community is that the stroke therapy of the future will be richly multimodal, combining hyperacute neuroprotection, acute recanalization, clot recurrence prevention, and subacute neurorestoration (Table 1).

Clinical research in the brain-based ischemic stroke treatment approaches—acute neuroprotection and subacute neurorestoration—is being reinvigorated by new methodologies and reconceptualizations of prior approaches. In this article, these promising new developments are illustrated by examining current research on new uses for two nutritional supplements, magnesium sulfate and citicoline.