[Early reperfusion as a rationale from of therapy in ischemic stroke].

In the last few years considerable evidence has been seen making it clear that although focal neurological deficiency (or ischaemic stroke) develops in parallel with intracranial arterial occlusion, the irreversible damage neurons suffer (i e necrosis) in many parts of the ischaemic territory is delayed by several hours. After an occlusion of the middle cerebral artery, such a lapse is particularly evident in the region of the cerebral cortex, an area which could be considered as the most peripheral region of the ischaemic territory, also known as 'penumbra'. This article sets out to review the secondary events in time-dependent studies which show that many of the consequences of intracranial artery occlusion may be totally or partly reversible by reopening the artery 60 minutes after. The right middle cerebral artery (MCA) of some two hundred adult Wistar rats was blocked up by inserting a nylon monofilament through the outer carotid artery. In some of the animals such occlusion was resolved by removing the filament minutes or hours later whereas in others light from the MCA remained occluded until the end of the experiment seven days later. Many histological and histochemical analyses were performed as well as microscopic preparation for each subject to obtain information concerning the movement of circulating leucocytes and of platelets, the integrity of capillaries as opposed to a circulating macromolecule (mw: 43 kd), the development of neuronal necrosis and the relationship between neurological deficiency and the level of histological damage. Once the MCA was blocked, both neuronal necrosis and leukocyte movement followed a somewhat parallel course. A large number of necrotic neurons appeared in the next twelve hours, coinciding with the time most intravascular leukocytes (neutrophiles) take in making themselves visible around the area affected by the blocked artery. In any case, prior to the development of neuronal necrosis and of leucotaxis, significant abnormalities appear affecting the perivascular astrocytes and capillary endothelial cells. The structural changes in these cells, and especially tumefaction, are what cause important abnormalities in microvascular integrity appearing several hours before neuronal necrosis. To recap: a) despite the fact that leucocyte migration and progressive neuronal necrosis follow a parallel course in time, the casual relationship between these two physiopathological phenomena is still not firmly established: b) the structural changes affecting vascular endothelial cells and astrocytes could fulfill a primordial role in possible neuronal necrosis that in the context of an experimental infarct is not produced until six hours after arterial blockage; c) microvascular deterioration may be reversible by reopening the blockage if this is carried out at most 60 minutes afterwards. This point would suggest that selective treatment of ischaemic stroke patients using thrombotic agents or angioplasty could have beneficial effects.