title: Neuroprotection for ischaemic stroke: current status and challenges.
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.
authors.affiliation: Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, Department of Biology and Biotechnology, University of Pavia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Moretti
authors.affiliation: Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, Department of Biology and Biotechnology, University of Pavia, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Ferrari
authors.affiliation: Laboratory of Pharmacology and Molecular Medicine of Central Nervous System, Department of Biology and Biotechnology, University of Pavia, Italy. Electronic address: robertofederico.villa@unipv.it.
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Villa
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy* / Q000517:prevention & control
chemical_list: D018696:Neuroprotective Agents
keywords: Experimental, clinical studies; Ischaemic stroke; Neuroprotection; Neurorepair