title: Therapeutic approaches to vascular protection in ischemic stroke.
abstract: Reperfusion with recombinant tissue plasminogen activator (tPA) sometimes causes catastrophic hemorrhagic transformation (HT) in the ischemic brain. Consequently, the application of tPA has been strictly limited. Recent studies have indicated that matrix metalloproteinases (MMPs), especially MMP-9, play a critical role in blood brain barrier (BBB) disruption in the ischemic brain, leading to brain edema and HT. In the ischemic brain, free radicals and exogenous tPA itself can trigger MMP-9 activation through several signaling pathways containing LDL receptor-related protein (LRP) and proteinase-activated receptor 1 (PAR1). Therapeutic targeting of free radicals and MMP-9/t-PA related signaling pathways might be promising approaches to minimizing catastrophic HT in acute stroke patients. We provide an overview of the available scientific reports to improve our understanding of the mechanisms leading to HT, and highlight recent progress in the development of new therapeutic strategies for preventing HT in the post-stroke brain.
authors.affiliation: Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. tooy@dl.dion.ne.jp
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D002545:Brain Ischemia / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000473:pathology / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000503:physiopathology / Q000628:therapy*; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9