Toward a multimodal neuroprotective treatment of stroke

Stroke remains a common medical problem with importance attributable to the demographic changes in industrialized societies.

After years of setbacks, acute stroke therapy has finally emerged, including thrombolysis with tissue plasminogen activator (t-PA). However, t-PA treatment is limited by a narrow time window and side effects, so that only 3% of all stroke patients receive thrombolysis. Unimodal targeting of key events in stroke pathophysiology was not effective in providing long-term benefits, leading to negative results in previous clinical neuroprotective stroke trials. A successful future stroke therapy should approach multiple pathophysiological mechanisms besides revascularization at once, including reduction of t-PA-related side effects, prevention of cell death, stimulation of neuroregeneration, and plasticity.

Strategies targeting these processes include multiple combination therapies as well as treatment with multimodal drugs that interact with these mechanisms. Here, we review such combination approaches, and outline how this concept could be developed into future stroke treatment.