Targets for vascular protection after acute ischemic stroke.
BACKGROUND
Vascular damage caused by cerebral ischemia leads to edema, hemorrhage formation, and worsened outcomes in ischemic stroke patients. Therapeutic interventions need to be developed to provide vascular protection. The purpose of this review is to identify the pathophysiologic processes involved in vascular damage after ischemia, which may lead to strategies to provide vascular protection in ischemic stroke patients.


RESULTS
The pathologic processes caused by vascular injury after an occlusion of a cerebral artery can be separated into acute (hours), subacute (hours to days), and chronic (days to months). Targets for intervention can be identified for all 3 stages. Acutely, superoxide is the predominant mediator, followed by inflammatory mediators and proteases subacutely. In the chronic phase, proapoptotic gene products have been implicated.


CONCLUSIONS
Pharmacological agents designed to target specific pathologic and protective processes affecting the vasculature should be used in clinical trials of vascular protection after acute ischemic stroke.
Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Athens, Ga 30912-2450, USA. sfagan@mail.mcg.edu
Susan C
SC
Fagan
David C
DC
Hess
Elizabeth J
EJ
Hohnadel
David M
DM
Pollock
Adviye
A
Ergul
D000208:Acute Disease; D042682:Angiopoietins / Q000502:physiology; D000804:Angiotensin II / Q000502:physiology; D000975:Antioxidants / Q000627:therapeutic use; D017209:Apoptosis; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000628:therapy*; D002536:Cerebral Arteries / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D002908:Chronic Disease; D019332:Endothelin-1 / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D020782:Matrix Metalloproteinases / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D009504:Neutrophils / Q000502:physiology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology; D014657:Vasculitis / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*
D042682:Angiopoietins; D000975:Antioxidants; D019332:Endothelin-1; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; D000804:Angiotensin II; D020782:Matrix Metalloproteinases