title: Tactics for vascular protection after acute ischemic stroke.
abstract: BACKGROUND
  The vascular events that happen during ischemic stroke worsen outcomes in patients by causing edema, hemorrhagic transformation, and general neurologic tissue compromise. In the past 2 decades, clinical trials in patients after ischemic stroke focused on neuroprotection, but these strategies have failed in providing actual benefit. Vascular protection represents a new field to be explored in acute ischemic stroke in order to develop new approaches to therapeutic intervention.
  
  
  OBJECTIVE
  We identified tactics likely to provide vascular protection in patients with ischemic stroke. These tactics are based on knowledge of the molecular processes involved.
  
  
  RESULTS
  The pathologic processes due to vascular injury after an occlusion of a cerebral artery can be separated into acute (those occurring within hrs), subacute (hrs to days), and chronic (days to mo). Targets for intervention can be identified for all three stages. In the acute phase, superoxide is the predominant mediator, followed by inflammatory mediators and proteases in the subacute phase. In the chronic phase, proapoptotic gene products have been implicated. Many already-marketed therapeutic agents (statins, angiotensin modulators, erythropoietin, minocycline, and thiazolidinediones), with proven safety in patients, have been shown to have activity against some of the key targets of vascular protection.
  
  
  CONCLUSIONS
  Currently available pharmacologic agents are poised for clinical trials of vascular protection after acute ischemic stroke.
authors.affiliation: Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, Georgia 30912-2450, USA. sfagan@mail.mcg.edu
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.forename: David C
authors.initials: DC
authors.lastname: Hess
authors.forename: Livia S
authors.initials: LS
authors.lastname: Machado
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Hohnadel
authors.forename: David M
authors.initials: DM
authors.lastname: Pollock
authors.forename: Adviye
authors.initials: A
authors.lastname: Ergul
mesh_terms: D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001921:Brain / Q000098:blood supply*; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D002545:Brain Ischemia / Q000150:complications*; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D002908:Chronic Disease; D004921:Erythropoietin / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008911:Minocycline / Q000627:therapeutic use; D020521:Stroke / Q000150:complications*; D045162:Thiazolidinediones / Q000627:therapeutic use; D015912:Thrombolytic Therapy
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D045162:Thiazolidinediones; D004921:Erythropoietin; D008911:Minocycline