How Healthy Is the Acutely Reperfused Ischemic Penumbra?

Because it is the main determinant of clinical recovery, early reperfusion of the ischemic penumbra has become the mainstay of acute stroke therapy. Although early permanent recanalization can be associated with spectacular and complete recovery, some patients in fact exhibit delayed or incomplete recovery, even despite small infarcts on late structural imaging. This might result from tissue inflammation and selective neuronal death/damage, two probably inter-related cellular events well described in the animal literature, precluding full functional restoration in the salvaged penumbra. However, impact of these processes on recovery may be complex because of the interplay with ongoing plasticity and the possible promoting effect of inflammation on the latter. Preliminary results from imaging studies of inflammation and selective neuronal loss after middle cerebral artery territory stroke, using radioligands of the central benzodiazepine receptor and the activated microglia, respectively, reviewed here, suggest these phenomena also exist in man, although their relationship with acute-stage hypoperfusion and their impact on clinical recovery, if any, remain poorly understood. Furthermore, their inter-relationships in the salvaged penumbra have not been addressed. Better understanding of these potentially harmful processes might help to maximize benefits from thrombolysis, and could also have implications for patients who enjoy spontaneous recanalization.