Trends in Neurosciences
Ischemic tolerance and endogenous neuroprotection
Section snippets
IP/IT is an archetypal, non-specific stress response
Susceptibility to cell injury from oxygen deprivation is highly variable in the animal kingdom but all animals have developed strategies to cope with restricted substrate delivery. Accordingly, several groups have recently used invertebrates to study IP/IT [6]. Although it is unlikely that inducible protection against stroke is an evolutionary advantage, it is likely that mechanisms that protect against global hypoxia can also protect against stroke.
Because tissue damage in ischemia is the
Learning from Mother Nature: IP/IT as model to study endogenous neuroprotective mechanisms
Incongruity between the striking rate of stroke occurrence (about one every 42 s in the USA alone) and the stumbling pace at which effective stroke therapy is being developed gives impetus to the exploration of novel strategies for neuroprotection. Induction of IP/IT has been suggested as a promising clinical strategy to prepare the brain for situations when ischemia is anticipated (e.g. during surgery of the heart and brain, and in high-risk stroke patients). Here, we propose that possibly an
Mechanisms of IP/IT: complex and redundant signaling cascades
Numerous studies have investigated the signaling cascades of IP/IT in various in vitro and in vivo models. A more detailed review of the many mechanisms investigated so far has recently been published [4]. To facilitate the overview of established mechanisms, the processes of IP/IT induction can be viewed in the temporal order of their involvement and activation: as a sensor of the sub-threshold stimulus, as a transducer of the stimulus, and as effectors of the preconditioning response (Fig. 3).
Open issues and future challenges
There are numerous clinical conditions and procedures in which ischemia of the brain is anticipated (e.g. surgery of the heart and brain). Because IP/IT seems to exist in humans 19, 20, and because there are experimental IP/IT paradigms that involve clinically approved drugs (desferroxamine and erythropoietin [45], isoflurane [29] and KATP openers [46]), IP/IT might be exploited in clinical neurology to protect the brain. To this end, several groups are currently planning clinical trials to
Concluding remarks
We postulate that IP/IT research can guide investigators to targets for acute therapy against the consequences of brain ischemia that would have been difficult to discern by intuition or deduction. Although there are many unresolved issues at the bench, IP/IT strategies could soon be at the bedside in carefully planned clinical trials.
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