Abstract: In terms of a purely neuronal concept of evolving susceptibility to ischemia or hypoxia, the penumbral phenomenon around a focus of infarction might determine how the cerebral tissues either provoke further progressive neuronal injury or else promote neuronal recovery. Such tissue participation would thus develop as interstitial/vasogenic edema or even as intracellular cytotoxic effect. Integral tissue involvement would promote vascular and hemodynamic factors in determining neuronal outcome. Vascular blood supply and mechanisms linked to cellular energy stores might indicate the participation of neuronal pathways of potential susceptibility or of recoverability that are fully dependent on strict evolving effect. Neuronal ischemia would constitute a phenomenon of tissue evolution as reflected in the penumbra around a focus of already established infarction. The presence of a core of ischemic necrosis in cerebral tissues would determine evolving mechanisms in the penumbral zone determining pathologic and clinical characterization of progressive neuronal ischemia/hypoxia. The individual neuron would constitute one expression of many in a vascular occlusive series of phenomena associated with progression or nonprogression of such neuronal injury. Active tissue participation might develop in directly and indirectly induced cell injury and cell death as either necrosis or apoptosis. Indeed, a central role for tissue vascularity might perhaps determine either cell apoptosis or necrosis in ischemic events of progression or nonprogression.