Experimental and human ischaemia: is the penumbra present in human ischaemic stroke?

Experimental occlusion of the middle cerebral artery and the reduction of cerebral blood flow (CBF) below 15 ml/100 gm/per minute cause failure of the somatosensory evoked response and lethargy of cortical neurones. Increase of CBF to normal value normalises the bioelectrical activity within the "penumbra"--the zone surrounding the necrotic area. In this "risk zone" neurones can survive only a few hours. So the penumbra is a "therapeutic window" in which therapy can save some neurones from death. However, if decrease of CBF is continued, numerous cells within the penumbra gradually die. The phenomenon of the penumbra, based on experiments, was applied to human ischaemic stroke; however great differences between experimental and human brain ischaemia do exist. The human course of disease and the size of necrotic lesion depend on numerous additional factors. The three very important critical values of CBF which decrease in human brain ischaemia are difficult to examine. New imaging methods play a great diagnostic role in searching for the penumbra, but their diagnostic possibilities and results are limited. In the short-time duration of the therapeutic window both CT and MRI often do not indicate ischaemic lesion. So, it is not known whether the penumbra is present or not. Conclusive estimation of MRI diffusion-weighted imaging and perfusion-imaging and of their coefficient is impossible to obtain in the time exceeding the "therapeutic window'" Numerous additional various diseases and compensatory vascular mechanisms influence the necrotic zone in human focal ischaemia. Probably for this reason a difficulty in the estimation of the penumbra in human is observed. So, it seems that the penumbra--the therapeutic window or risk zone--in human probably occurs only in some cases. It may be one of numerous reasons for the limited effectiveness of ischaemic stroke therapy. It is not known when the penumbra is overspread with oedema, which always appears to a greater or a lesser degree. Maybe the efforts of experimental investigators, physicians and pharmacologists should also be taken into consideration to find drugs decreasing oedema and BBB permeability.