The ischemic penumbra

In 1977, Symon et al.1 adapted the term ischemic penumbra from astronomy to describe the region of susceptible brain between the necrotic core and normal brain (the umbra, or shadow) in a model of focal ischemia. The limits of the ischemic penumbra were defined by the thresholds of electrical and membrane failure; neurons in the penumbra were defined as structurally intact, with their ultimate fate dependent on the duration of ischemia, thus uniting reduction in cerebral blood flow (CBF) and cerebral function and metabolism. Subsequent studies suggest a more complex process. During the initial few hours of vascular occlusion, different neuronal functions break down at widely varying CBFs. At declining flow rates, protein synthesis is first inhibited; this is followed by anaerobic glycolysis, the release of neurotransmitters, impaired energy metabolism, and finally membrane depolarization2; in ischemia models, this can precisely define, temporally and spatially, the penumbra. The imaging of the penumbra in humans can be performed by several techniques, but is challenging. PET first demonstrated the ischemic penumbra, defined by PET parameters of CBF,3 cerebral metabolic rate of oxygen (CMRO2), and …