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.
References (78)
Neuronal ischaemic preconditioning
Trends Pharmacol. Sci.
(2000)Pathobiology of ischaemic stroke: an integrated view
Trends Neurosci.
(1999)‘Ischemic tolerance’ phenomenon found in the brain
Brain Res.
(1990)Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice is strain dependent
Brain Res.
(2000)Lipopolysaccharide-induced ischemic tolerance is associated with increased levels of ceramide in brain and in plasma
Brain Res.
(2001)Polyunsaturated fatty acids induce ischemic and epileptic tolerance
Neuroscience
(2002)Adaptation of adult brain tissue to anoxia and hypoxia in vitro
Brain Res.
(1986)Lipopolysaccharide pretreatment protects from renal ischemia/reperfusion injury: possible connection to an interleukin-6-dependent pathway
Am. J. Pathol.
(2000)Is CREB a key to neuronal survival?
Trends Neurosci.
(2000)Adaptation to myocardial stress in disease states: is preconditioning a healthy heart phenomenon?
Trends Pharmacol. Sci.
(1998)
Hippocampal kindling protects several structures from the neuronal damage resulting from kainic acid-induced status epilepticus
Brain Res.
Mechanisms of cardiac preconditioning: ten years after the discovery of ischemic preconditioning
J. Surg. Res.
Mechanism, origin, and evolution of anoxia tolerance in animals
Comp. Biochem. Physiol. B Biochem. Mol. Biol.
Animal response to drastic changes in oxygen availability and physiological oxidative stress
Comp. Biochem. Physiol. C. Toxicol. Pharmacol.
Effects of adenosine on synaptic transmission in hippocampal slices from hibernating and warm-acclimated Turkish hamsters and rats
Neurosci. Lett.
Brain antioxidant regulation in mammals and anoxia-tolerant reptiles: balanced for neuroprotection and neuromodulation
Comp.Biochem. Physiol. C. Toxicol. Pharmacol.
Preconditioning-mediated neuroprotection through erythropoietin?
Lancet
Alterations in lysosomes (intracellular enzymes) during shock; effects of preconditioning (tolerance) and protective drugs
Int. Anesthesiol. Clin.
Ischemic tolerance in the brain
Neurology
Ischemic tolerance
J. Cereb. Blood Flow Metab.
Cerebral ischemic preconditioning: an experimental phenomenon or a clinical important entity of stroke prevention?
J. Neurol.
Neuronal tolerance to O2 deprivation in Drosophila: novel approaches using genetic models
Neuroscientist
Focal ischemic preconditioning induces rapid tolerance to middle cerebral artery occlusion in mice
J. Cereb. Blood Flow Metab.
Spreading depression induces tolerance of cortical neurons to ischemia in rat brain
J. Cereb. Blood Flow Metab.
Respiratory chain inhibition induces tolerance to focal cerebral ischemia
J. Cereb. Blood Flow Metab.
Transient hyperthermia protects against subsequent forebrain ischemic cell damage in the rat
Neurology
Ischemic tolerance in the rat neocortex following hypothermic preconditioning
J. Neurosurg.
Cerebellar stimulation reduces inducible nitric oxide synthase expression and protects brain from ischemia
Am. J. Physiol.
Serial analysis of gene expression identifies metallothionein-II as major neuroprotective gene in mouse focal cerebral ischemia
J. Neurosci.
Attenuated stroke severity after prodromal TIA: a role for ischemic tolerance in the brain?
Stroke
Do transient ischemic attacks have a neuroprotective effect?
Neurology
Rapid preconditioning protects rats against ischemic neuronal damage after 3 but not 7 days of reperfusion following global cerebral ischemia
J. Cereb. Blood Flow Metab.
Ischemic preconditioning preserves mitochondrial function after global cerebral ischemia in rat hippocampus
J. Cereb. Blood Flow Metab.
Activation of mitochondrial ATP-dependent potassium channels protects neurons against ischemia-induced death by a mechanism involving suppression of Bax translocation and cytochrome c release
J. Cereb. Blood Flow Metab.
Ischemic preconditioning is capable of inducing mitochondrial tolerance in the rat brain
Anesthesiology
Hypoxic preconditioning induces changes in HIF-1 target genes in neonatal rat brain
J. Cereb. Blood Flow Metab.
Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia-inducible factor-1 and its target genes, erythropoietin and VEGF, in the adult mouse brain
J. Cereb. Blood Flow Metab.
Neuroprotection and P450 2C11 upregulation after experimental transient ischemic attack
Stroke
Tolerance against ischemic neuronal injury can be induced by volatile anesthetics and is inducible NO synthase dependent
Stroke
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