title: Cerebral blood flow alteration in neuroprotection following cerebral ischaemia.
abstract: The best neuroprotectant for acute ischaemic stroke would always be the rapid return of oxygen and glucose to physiological levels. This is currently provided by thrombolysis which restores blood flow to the ischaemic region. The attempt to confer neuroprotection by targeting the brain parenchyma has shown promise in experimental stroke models, but has unequivocally failed to translate to the clinic. Neuroprotective therapy primarily targets the biochemical cascade that produces cell death following cerebral ischaemia. However, these agents may also alter signal transduction that controls cerebral blood flow, for example glutamate, which may affect the outcome after ischaemia. In these cases, neuroprotection may potentially be due to the improved access to oxygen and glucose rather than biochemical prevention of cell death. Improvement in cerebral blood flow is an important but often overlooked effect of neuroprotective therapy, analogous to the protective effects of drug-induced hypothermia. This short review will discuss cerebral blood flow alteration and protection of the brain in the context of ischaemic preconditioning, oxygen sensing and thrombolysis. Future neuroprotection studies in cerebral ischaemia require stringent monitoring of cerebral blood flow, plus other physiological parameters. This will increase the chances that any protection observed may be able to translate to human therapy.
authors.affiliation: Acute Stroke Programme, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Sutherland
authors.forename: Michalis
authors.initials: M
authors.lastname: Papadakis
authors.forename: Ruo-Li
authors.initials: RL
authors.lastname: Chen
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Buchan
mesh_terms: D002545:Brain Ischemia; D002560:Cerebrovascular Circulation / Q000187:drug effects; D006801:Humans; D000066829:Neuroprotection; D018696:Neuroprotective Agents / Q000494:pharmacology; D020521:Stroke
chemical_list: D018696:Neuroprotective Agents