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RESEARCH PRODUCT

Fostering Poststroke Recovery: Towards Combination Treatments.

subject

description

Despite countless experimental studies demonstrating neuroprotective effects in the treatment of acute ischemic stroke, they all could not live up their promises when it came to translation into patients. Recent research therefore increasingly shifted to therapies enhancing poststroke recovery with the important advantage of a much wider time window up to several months. To further increase poststroke recovery, the combination of different therapy principles is a logical step. However, several burning questions concerning the modus of combination are unresolved. This review will briefly mention the principle poststroke recovery approaches and discuss the mostly used combination designs. In the second part, the central issues of combination paradigms will be discussed, and some most promising paradigms will be presented. Ischemic stroke immediately triggers a cascade of molecular and cellular events in the perilesional tissue which both further escalate the primary damage but contrariwise also are part of an endogenous response aided to reduce brain injury. Even more, these primarily adverse effects are the starting point to remove irreversibly damaged tissue and to repair and to reorganize surviving structures with remapping of related brain regions later on. The alterations in the peri-ischemic brain become the cornerstone for a particularly sensitive period of enhanced poststroke plasticity with a short window of a regenerative friendly milieu (Zeiler and Krakauer).1 This is reflected by the fact that the poststroke recovery is widely restricted to the first 3 to 6 months in human patients and about 1 month in rodent models of ischemic stroke. One of the key events thought to prepare the ground for regenerative processes plays the inflammatory response which starts very early after ischemia.2 Triggered by inflammatory cells and the activation of extracellular matrix-degrading enzymes, the tissue surrounding the infarct becomes permissive and allows sprouting of axonal processes with the formation of …