Preconditioning paradigms and pathways in the brain.
ABSTRACT Preconditioning is a phenomenon in which the brain protects itself against future injury by adapting to low doses of noxious insults. Preconditioning stimuli include ischemia, low doses of endotoxin, hypoxia, hypothermia and hyperthermia, cortical spreading depression, anesthetics, and 3-nitropropionic acid, among others. Understanding of the mechanisms underlying preconditioning has been elusive, but NMDA receptor activation, nitric oxide, inflammatory cytokines, and suppression of the innate immune system appear to have a role. Elucidation of the endogenous cell survival pathways involved in preconditioning has significant clinical implications for preventing neuronal damage in susceptible patients.
SourceAvailable from: Carina R Boeck[Show abstract] [Hide abstract]
ABSTRACT: N-methyl-D-aspartate (NMDA) preconditioning is induced by subtoxic doses of NMDA and it promotes a transient state of resistance against subsequent lethal insults. Interestingly, this mechanism of neuroprotection depends on adenosine A1 receptors (A1R), since blockade of A1R precludes this phenomenon. In this study we evaluated the consequences of NMDA preconditioning on the hippocampal A1R biology (i.e. expression, binding properties and functionality). Accordingly, we measured A1R expression in NMDA preconditioned mice (75mg/kg, i.p.; 24hours) and showed that neither the total amount of receptor, nor the A1R levels in the synaptic fraction was altered. In addition, the A1R binding affinity to the antagonist [(3)H] DPCPX was slightly increased in total membrane extracts of hippocampus from preconditioned mice. Next, we evaluated the impact of NMDA preconditioning on A1R functioning by measuring the A1R-mediated regulation of glutamate uptake into hippocampal slices and on behavioral responses in the open field and hot plate tests. NMDA preconditioning increased glutamate uptake into hippocampal slices without altering the expression of glutamate transporter GLT-1. Interestingly, NMDA preconditioning also induced antinociception in the hot plate test and both effects were reversed by post-activation of A1R with the agonist CCPA (0.2mg/kg, i.p.). NMDA preconditioning or A1R modulation did not alter locomotor activity in the open field. Overall, the results described herein provide new evidence that post-activation of A1R modulates NMDA preconditioning-mediated responses, pointing to the importance of the cross-talk between glutamatergic and adenosinergic systems to neuroprotection. Copyright © 2014. Published by Elsevier B.V.Behavioural Brain Research 12/2014; 282. DOI:10.1016/j.bbr.2014.12.056 · 3.39 Impact Factor
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ABSTRACT: Experiments on conscious rabbits using spectral coherence analysis addressed the nature of changes in brain electrical activity following spreading depression waves in initial (1–4) and subsequent (5–10) experiments. In the initial experiments, long-term unilateral changes in the EEG were seen on the side ipsilateral to the spreading depression wave, these consisting of increases in the power of biopotentials in the delta and beta frequency ranges with simultaneous suppression of power in the gamma range. There was a reduction in the coherence of biopotentials between symmetrical points in the two hemispheres. Subsequent experiments showed generalized (across both hemispheres) increases in electrical activity in the delta and theta frequency ranges with increases in coherence in the beta range. This generalized activity was cyclic in nature and was seen over long periods of time (2–3 h) after passage of single spreading depression waves, it prevented the spreading of subsequent waves in the neocortex, decreasing the probability that they would arise, and this could reach the level of complete blockade. Thus, spreading depression waves provoke the appearance of synchronized beta waves in overall brain electrical activity and actively influenced the properties of recurrent waves.Neuroscience and Behavioral Physiology 02/2014; 44(2). DOI:10.1007/s11055-014-9887-4
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ABSTRACT: This review presents the results of our own studies and published data on a current problem of neurobiology and basic medicine – discovery of the mechanisms of increases in the resistance of the brain to the effects of extreme factors. Most attention is paid to the molecular-cellular and hormonal mechanisms of hypoxic preconditioning-induced increases in the tolerance of the brain to presentation of harmful hypoxia and psychoemotional and traumatic stress. The basic hormonal and intracellular proadaptive cascade processes mediating the neuroprotective actions of hypoxic preconditioning are considered. The dynamics of molecular-level developmental mechanisms of induced tolerance of vulnerable brain formations (hippocampus, neocortex), including the phases of induction, transformation, and expression, are assessed. New data on preconditioning-related “cross-tolerance” of the brain, increasing the resistance of the brain not only to hypoxia, but also to different types of stressors, are presented. A first description of the neuroprotective effects of hypoxic post-conditioning is provided.Neuroscience and Behavioral Physiology 09/2013; 43(7). DOI:10.1007/s11055-013-9813-1