Neuroinflammatory responses in experimental and human stroke lesions

Neuroinflammation has been suggested as an attractive treatment target in stroke, since it offers a broader therapeutic window in comparison to currently established thrombolytic approaches. Inflammatory cells of both the innate and the adaptive immune system have been identified in experimental as well as human stroke lesions. In animal models, various therapeutic strategies targeting neuroinflammation have shown beneficial effects, however, translation to human disease has so far been disappointing. Comparisons of the numerous experimental findings with until now rather limited human data reveal that despite similarities in the core signature of the inflammatory reaction, human stroke lacks clearly definable temporal and spatial sequences of lesion maturation that can be generalized and applied for a large patient population. Thus, in comparison with well-timed animal models with a clear succession of pathogenic mechanisms, precise and stage-dependent targeting of neuroinflammation in human stroke patients will be difficult to achieve. In addition, the contribution of different components of the innate and adaptive immune system quantitatively varies between humans and experimental animals and even between different modes of ischemia induction in animal models. Finally, human stroke lesions develop on a basis of age-dependent microglia pre-activation, which may have major impact on the further activation and functional differentiation of these cells. Knowledge about neuroinflammation in stroke patients, however, is currently limited and it has to be determined in future studies to what extent different causes of stroke and different co-morbidities in the patients result in distinct patterns of inflammation.