Improving outcome after stroke: overcoming the translational roadblock

Cerebrovasc Dis. 2008;25(3):268-78. doi: 10.1159/000118039. Epub 2008 Feb 22.

Abstract

Stroke poses a massive burden of disease, yet we have few effective therapies. The paucity of therapeutic options stands contrary to intensive research efforts. The failure of these past investments demands a thorough re-examination of the pathophysiology of ischaemic brain injury. Several critical areas hold the key to overcoming the translational roadblock: (1) vascular occlusion: current recanalization strategies have limited effectiveness and may have serious side effects; (2) complexity of stroke pathobiology: therapy must acknowledge the 'Janus-faced' nature of many stroke targets and must identify endogenous neuroprotective and repair mechanisms; (3) inflammation and brain-immune-system interaction: inflammation contributes to lesion expansion, but is also instrumental in lesion containment and repair; stroke outcome is modulated by the interaction of the injured brain with the immune system; (4) regeneration: the potential of the brain for reorganization, plasticity and repair after injury is much greater than previously thought; (5) confounding factors, long-term outcome and predictive modelling. These 5 areas are linked on all levels and therefore need to be tackled by an integrative approach and innovative therapeutic strategies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Biomedical Research*
  • Brain / blood supply
  • Brain / drug effects*
  • Brain / pathology
  • Brain / physiopathology
  • Brain Ischemia / complications*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy
  • Cerebrovascular Circulation / drug effects
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Humans
  • Immune System / drug effects
  • Immune System / physiopathology
  • Inflammation / drug therapy
  • Ischemic Preconditioning*
  • Nerve Regeneration / drug effects
  • Neurons / drug effects
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Research Design
  • Stroke / etiology
  • Stroke / pathology
  • Stroke / physiopathology
  • Stroke / therapy*
  • Thrombolytic Therapy* / adverse effects
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Neuroprotective Agents