Ischemic stroke intervention requires mixed cellular protection of the penumbra.

The failure of many acute stroke intervention clinical trials has raised significant concerns regarding neuroprotection alone as a strategy for therapeutic intervention in the treatment of stroke. 'Neuroprotection' strategies typically have focused on neurons and the neurotoxic environment observed under ischemic conditions; however, the complex processes that occur post-stroke require the targeting of multiple factors and cells, including glia, vascular and inflammatory cells, and multiple types of cell death (eg, including the death of axons/white matter). Although the ischemic penumbra (the brain areas bordering the ischemic core) can be salvaged by interventions much later post-stroke than the ischemic core, future interventions need to target the multiple cell types involved in the evolution of the penumbra to infarction (ie, to improve treatment outcome by maintaining the integrity of the brain at risk for injury post-stroke).