Lancet neurology
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Metaphor has an important role in the discussion of scientific discovery because it enables researchers to talk about things of which their understanding is incomplete. Alzheimer's disease (AD) can be seen as a journey down a path, which becomes steadily less pleasant and ends in a wholly undesirable destination. To further the metaphor, treatments can be seen as attempts to help the patient return to the starting point, to slow the journey, or to stop at some point on the path. ⋯ This metaphor has practical implications for clinical trials. It highlights the importance of individualised outcome measures that incorporate patients' preferences and should encourage us to develop better means of enabling the recovery of self. To understand how there can be treatment success short of cure, without knowing at the outset what form that success may take, will require systematic observation and careful description of patients' experiences.
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Activity-dependent long-term potentiation (LTP) of excitatory neurotransmission underlies specific forms of associative learning and memory. A brief period of energy deprivation induces LTP in specific subsets of neurons; this synaptic plasticity might contribute to the delayed effects of brain ischaemia. ⋯ On the basis of recent studies, we propose that pathological plasticity induced by energy deprivation can play a part in delayed neuronal death in the hippocampus and the striatum after global ischaemia and in the conversion of ischaemic penumbra to infarct core after focal ischaemia. We discuss evidence that ischaemia could also induce protective and reparative forms of neuronal plasticity that may play a part in ischaemic tolerance and poststroke recovery.