title: PPARs: a potential target for a disease-modifying strategy in stroke.
abstract: Stroke is one of the major causes of mortality and disability in adults in industrialized countries. Despite numerous preclinical studies and clinical trials in the field of cerebral ischemia, no pharmacological agent has been validated in the treatment of acute ischemic, except thrombolysis. Cerebral ischemia is not only a neuronal disease but it affects the entire neurovascular unit. The therapeutic strategy in stroke should be more global and combine preventive approaches, acute phase treatment and long-term care to improve recovery and prevent or treat affective and cognitive post-stroke consequences. There is an imperative need to develop disease-modifying drugs, which should be able to induce neuroprotection, to serve as adjuvants for thrombolysis by decreasing the hemorrhagic risk and to limit the long-term post-stroke consequences. This review presents the potential effects of Peroxisome Proliferator-Activated Receptors (PPARs) and of their agonists in stroke. We focus on each PPAR receptor and detail their implication in stroke. PPARs are nuclear receptors, acting as ligand-dependent transcription factors. They are expressed in the neurovascular unit that suggests that PPARs could play a role in stroke. Indeed, it has been shown that they are able to interfere with pathways implicated in the pathophysiology of stroke. They could be an answer to this disease-modifying drug concept, being able to act on the different phases of ischemia.
authors.affiliation: EA 1046 - Département de Pharmacologie médicale, University Lille Nord de France, Université de Lille 2 - Faculté de Médecine, Centre Hospitalier Universitaire, Institut de Médecine Prédictive et de Recherche Thérapeutique, Lille, France.
authors.forename: Thavarak
authors.initials: T
authors.lastname: Ouk
authors.forename: Camille
authors.initials: C
authors.lastname: Potey
authors.forename: Sophie
authors.initials: S
authors.lastname: Gautier
authors.forename: Michèle
authors.initials: M
authors.lastname: Bastide
authors.forename: Dominique
authors.initials: D
authors.lastname: Deplanque
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: Patrick
authors.initials: P
authors.lastname: Duriez
authors.forename: Didier
authors.initials: D
authors.lastname: Leys
authors.forename: Régis
authors.initials: R
authors.lastname: Bordet
mesh_terms: D000328:Adult; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D018696:Neuroprotective Agents / Q000494:pharmacology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists* / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D047492:Peroxisome Proliferator-Activated Receptors