Elements of cerebral microvascular ischaemia.
Although neuronal cells have long been thought to be the prime target of ischaemic insults, events which occur at the blood-vascular-parenchymal interface are necessary for the initiation of ischaemic tissue injury. This cascade of microvascular events includes fibrin accumulation, endothelium expression of leukocyte adhesion receptors, breakdown of the basal laminae with loss of astrocyte and endothelial cell contacts leading to blood-brain barrier disruption and consequently oedema formation and haemorrhagic transformation. Potential stroke treatments have been studied in the clinic and many have not been particularly successful, probably due to the delicate balance between improved outcome and adverse reactions as well as the window of opportunity for drug treatment after symptom onset. The only acute intervention trial demonstrating any benefit in patients was that of intravenous tissue plasminogen activator (tPA), administered within 3 h of the onset of symptoms of ischaemic stroke. Such treatment improved clinical outcome at 3 months, although there was an increased incidence of symptomatic haemorrhage [New Engl. J. Med. 333 (1995) 1581]. The recent progress made in defining the mechanisms involved in the initiation of ischaemic events, as described in this review, may lead to the identification of new strategies for intervention in the ischaemic cascade.
Petty
M A
MA
CNS Pharmacology, Aventis Pharmaceuticals, Inc., Route 202-206, P.O. Box 6800, Bridgewater, NJ 08807, USA. margaret.petty@aventis.com
Wettstein
J G
JG
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D002543:Cerebral Hemorrhage / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004487:Edema / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology*; D016028:Receptors, Leukocyte-Adhesion / Q000378:metabolism
D016028:Receptors, Leukocyte-Adhesion; D005337:Fibrin