TRENDS AND FUTURE-DEVELOPMENTS IN THE PHARMACOLOGICAL TREATMENT OF ACUTE ISCHEMIC STROKE

Stroke stands as the third leading cause of death. It makes great dema nds on patients, who must not only survive the complications of the ac ute stages, but must cope then with the great physical and economic co sts of long-term disabilities. Therefore, there is urgent need to esta blish generally useful regimens for the acute treatment of ischaemic s troke. Three treatment approaches are based upon pathophysiologic conc epts derived from experimental work with focal cerebral ischaemia. The se include pharmacologic strategies for arterial recanalisation, inhib ition of inflammatory processes and neural protection. Focal cerebral ischaemia secondary to occlusion of a brain supplying artery initiates neuronal and microvascular events, and the simultaneous processes of inflammation which further injure tissue. The use of plasminogen activ ators to mediate thrombus and lysis in the acute setting has been show n to be clinically beneficial. Further work with arterial reperfusion strategies is under way. Early clinical studies with polymorphonuclear leukocyte-dependent endothelial adhesion receptor antagonists are bei ng completed, but a strategy has yet to emerge. A large effort examini ng the potential efficacy of agents which may stabilise or protect neu rons from ischaemic injury has shown promise in experimental models, a nd has been translated into clinical trials. Experimental work, and li mited clinical experience, have indicated that: (a) the time window fo r intervention is important in limiting ischaemic and inflammatory inj ury, and for reducing the risk of haemorrhagic transformation; (b) put ative neuroprotective strategies may potentially elongate the time int erval for treatment; and (c) limitations from the adverse effects of p lasminogen activators and of agents which beneficially affect neuronal dysfunction during ischaemia must yet be overcome. This review survey s pharmacological approaches currently undergoing evaluation which pro vide the goal of establishing effective strategies for the treatment o f patients with acute cerebral ischaemia.