General introduction

Stroke is still the third cause of death and the first cause of chronic, highly disabling disease because of the frequent neurological sequelae affecting sensorimotor integration, movement programming and execution, walking, language, balance, mood and sensory perception. It is a well-accepted notion that, following the acute ischemic block of blood perfusion, there is a central core of dead neurons circumscribed by a shell of so-called ischemic penumbra, where the neurons adjacent to the damaged core are functionally blocked but still alive, because of the suboptimal flow from arterioles and capillaries and collaterals from the bed of vessels in the lesional periphery. This situation is of relatively brief duration (from hours to few days) and is followed either by a full recovery of the non-functioning, but still living, neurons (with a rapid, partial or total restoration of the lost functions) or by a complete loss of the perilesional contingent of brain cells with consequent stabilization of the clinical picture, i.e. the presence of more or less severe deficits. Several mechanisms contribute to the final volume of the lesioned tissue; from what can be inferred from the ischemia/reperfusion animal model, they include: ‘inflammatory-like’ reactions in which cytokines (mainly interleukin-1 and tumour necrosis factor) attract polymorphonuclear leukocytes, which create mechanical obstruction to erythrocytes' circulation by adherence to corresponding endothelial cell ligands, as well as becoming a source of oxygen free radicals (including nitric oxide, superoxide and peroxynitrite; del Zoppo & Garcia, 1995); later, a platelet activating factor induces platelets aggregation in the damaged area of microcirculation; in the core of the ischemic area, neuronal death may be mediated by the effects of excitatory neurotransmitters, e.g. glutamate which promotes calcium influx in the injured cells, and the accumulation of lactic acid as the result of a metabolic switch to anaerobiosis (Garcia et al., 1994).