Improving outcome after stroke: overcoming the translational roadblock.
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.
Endres
Matthias
M
Department of Neurology, Center for Stroke Research, Charité, Berlin, Germany.
Engelhardt
Britta
B
Koistinaho
Jari
J
Lindvall
Olle
O
Meairs
Stephen
S
Mohr
Jay P
JP
Planas
Anna
A
Rothwell
Nancy
N
Schwaninger
Markus
M
Schwab
Martin E
ME
Vivien
Denis
D
Wieloch
Tadeusz
T
Dirnagl
Ulrich
U
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D035843:Biomedical Research; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology; D007249:Inflammation / Q000188:drug therapy; D019194:Ischemic Preconditioning; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012107:Research Design; D020521:Stroke / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000009:adverse effects; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents