Preconditioning provides neuroprotection in models of CNS disease: Paradigms and clinical significance

Abstract

Preconditioning is a phenomenon in which brief episodes of a sublethal insult induce robust protection against subsequent lethal injuries. Preconditioning has been observed in multiple organisms and can occur in the brain as well as other tissues. Extensive animal studies suggest that the brain can be preconditioned to resist acute injuries, such as ischemic stroke, neonatal hypoxia/ischemia, trauma, and agents that are used in models of neurodegenerative diseases, such as Parkinson’s disease and Alzheimer’s disease. Effective preconditioning stimuli are numerous and diverse, ranging from transient ischemia, hypoxia, hyperbaric oxygen, hypothermia and hyperthermia, to exposure to neurotoxins and pharmacological agents. The phenomenon of “cross-tolerance,” in which a sublethal stress protects against a different type of injury, suggests that different preconditioning stimuli may confer protection against a wide range of injuries. Research conducted over the past few decades indicates that brain preconditioning is complex, involving multiple effectors such as metabolic inhibition, activation of extra- and intracellular defense mechanisms, a shift in the neuronal excitatory/inhibitory balance, and reduction in inflammatory sequelae. An improved understanding of brain preconditioning should help us identify innovative therapeutic strategies that prevent or at least reduce neuronal damage in susceptible patients. In this review, we focus on the experimental evidence of preconditioning in the brain and systematically survey the models used to develop paradigms for neuroprotection, and then discuss the clinical potential of brain preconditioning. In a subsequent components of this two-part series, we will discuss the cellular and molecular events that are likely to underlie these phenomena.

Lipopolysaccharide-Induced Preconditioning Attenuates Apoptosis and Differentially Regulates TLR4 and TLR7 Gene Expression after Ischemia in the Preterm Ovine Fetal Brain

“…However, our finding that the severity of injury is not increased when ischemia is induced only 4 h after exposure to LPS is in contrast to the finding of sensitization to HI injury in the neonatal rat [18]. This difference is likely to reflect the repeated LPS exposure in the present study resulting in some degree of self-tolerance and cross-tolerance, as observed in a variety of models of brain injury [67]. …”

Spontaneous Pre-Existing Hypoxia Does Not Affect Brain Damage after Global Cerebral Ischaemia in Late-Gestation Fetal Sheep

“…These findings of course are related to discrete events, whereas in the present study, stable, mild hypoxia was present for 24 h or more before cerebral ischaemia, which is well within the typical interval required to induce preconditioning [22] . Given that fetal body weight was less in the pre-existing hypoxia group, it is very likely that relative placental restriction was present compared to normoxic animals.…”

The role of p38MAPK signal pathway in the neuroprotective mechanism of limb postconditioning against rat cerebral ischemia/reperfusion injury

“…Nowadays, growing data suggested that non-pharmaceutical therapies might provide new approaches for stroke [7][8][9]. Ischemic postconditioning (IPost), in which repeated brief episodes of sublethal ischemia/reperfusion are applied after lethal ischemic episode and during reperfusion, has emerged as a promising method against I/R injury.…”