Ischemic Penumbra and Neuronal Death: Comments on the Therapeutic Window in Acute Stroke with Particular Reference to Thrombolytic Therapy

As reported in the literature, the moderate ischemia zone characterized by a rapid restoration of spontaneous and evoked electrical activity following reperfusion (up to 2 h of ischemia) is ''fully reversible''. But returning to the normal conditions does not prevent selective neuronal death, probably influenced by excitatory neurotransmitters. On the basis of animal studies, it is argued that several hours of ‘ischemic penumbra’ will eventually increase the neuronal loss even with a restoration of electrical activity. We studied acute-stroke cases (blood partition coefficient between damaged and normal hemisphere) with single-photon emission tomography (SPECT) using 99mTc hexamethyl-propylamine oxime as a tracer for cerebral perfusion imaging. The limits of moderate ischemia (penumbra) associated with the tissue survival structure (CT scanning) are discussed. We aim to define, in the early stage of the disease, the ischemic threshold compatible with a thrombolytic therapy and no unacceptable hemorrhagic risk. Clinical recovery can roughly, but in a clinically relevant way, evaluate neuronal death in ischemic penumbra in humans.