http://www.sciencedirect.com/science/article/pii/S016372581400165X
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Check access- DOI: 10.1016/j.pharmthera.2014.09.003
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Abstract
Stroke
is the third cause of death worldwide and the main cause of chronic,
severe adult disability. We focus on acute ischaemic stroke, which
accounts for approximately 80% of all strokes. The current therapy aims
at restoring cerebral blood flow within a narrow time window in order to
prevent damaging the “penumbra” which surrounds the infarct core.
Intravenous thrombolysis remains the fundamental treatment worldwide,
though not ideal for various restrictions and complications, limiting to
10% or less the percentage of patients treated within the appropriate
time window.
Neuroprotection is an alternative or
adjunct approach to thrombolysis, targeting cerebral parenchyma in the
acute ischaemic phase. Furthermore, neurorepair attempts to restore
neuronal function in the after-stroke phase in those patients (treated
or untreated) with significant impairment.
In the past
decades, the efficacy and safety of numerous candidate neuroprotective
agents were shown in various animal stroke models. However, in clinical
trials, promising pre-clinical studies have not been translated into
positive outcomes. Our review will analyse the possible reasons for this
failure and the new approaches and recommendations to overcome it, as
well as novel strategies targeting additional events in ischaemia
cascade. The combination of thrombolysis with pharmacological and
non-pharmacological neuroprotective approaches has also been tested.
Finally, the neurorepair strategy will be described with special
emphasis on the role of cell-based therapies and ischaemic conditioning.
Hopefully,
the future therapy of ischaemic stroke will encompass a combination of
neuroprotection (to stabilise penumbra), thrombolysis, antithrombotics
(for secondary prevention) and neurorepair based on cell therapy plus
rehabilitation.
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