So far, intravenous tissue-type plasminogen activator (tPA) and mechanical
removal of arterial blood clot (thrombectomy) are the only available treatments
for acute ischemic stroke. However, the short therapeutic window and the lack of
specialized stroke unit care make the overall availability of both treatments
limited. Additional agents to combine with tPA administration or thrombectomy to
enhance efficacy and improve outcomes associated with stroke are needed.
Stroke-induced inflammatory processes are a response to the tissue damage due to
the absence of blood supply but have been proposed also as key contributors to
all the stages of the ischemic stroke pathophysiology. Despite promising results
in experimental studies, inflammation-modulating treatments have not yet been
translated successfully into the clinical setting. This review will (a) describe
the timing of the stroke immune pathophysiology; (b) detail the immune responses
to stroke sift-through cell type; and (c) discuss the pitfalls on the
translation from experimental studies to clinical trials testing the therapeutic
pertinence of immune modulators.
Stroke represents a global challenge and is a leading cause of permanent disability worldwide. Despite much effort, translation of research findings to clinical benefit has not yet been successful. Failure of neuroprotection trials is considered, in part, due to the low quality of preclinical studies, low level of reproducibility across different laboratories and that stroke co-morbidities have not been fully considered in experimental models. More rigorous testing of new drug candidates in different experimental models of stroke and initiation of preclinical cross-laboratory studies have been suggested as ways to improve translation. However, to our knowledge, no drugs currently in clinical stroke trials have been investigated in preclinical cross-laboratory studies. The cytokine interleukin 1 is a key mediator of neuronal injury, and the naturally occurring interleukin 1 receptor antagonist has been reported as beneficial in experimental studies of stroke. In the present paper, we report on a preclinical cross-laboratory stroke trial designed to investigate the efficacy of interleukin 1 receptor antagonist in different research laboratories across Europe. Our results strongly support the therapeutic potential of interleukin 1 receptor antagonist in experimental stroke and provide further evidence that interleukin 1 receptor antagonist should be evaluated in more extensive clinical stroke trials.
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