Preconditioning paradigms and pathways in the brain.

Department of Neurosciences, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Cleveland Clinic Journal of Medicine (Impact Factor: 3.37). 04/2008; 75 Suppl 2:S77-82. DOI: 10.3949/ccjm.75.Suppl_2.S77
Source: PubMed

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.


Available from: Marc S Penn, Dec 23, 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Microglia are resident immunocompetent cells having important roles in innate immunity in the brains. In the present study, we found that a single lipopolysaccharide (LPS) administration significantly increased microglial proliferation in the fornix and dentate gyrus (DG) but not the cerebral cortex and corpus callosum of adult mice. LPS-induced microglial proliferation was especially robust at the white matter of the fornix. The density of microglia increased in the fornix and DG for roughly one week and returned to basal levels at least 20 days after a single LPS administration. Consecutive LPS administration did not induce such dramatic increase of microglial proliferation in the fornix. The inhibition of vascular endothelial growth factor signaling by AZD2171 largely suppressed LPS-induced increase of microglial proliferation in the fornix. In conclusion, the present study indicates that the hippocampal neuronal system have higher proliferative microglial capability against LPS-induced inflammatory administration compared with other brain regions.
    Journal of Neuroimmunology 05/2015; 285:31-46. DOI:10.1016/j.jneuroim.2015.05.014 · 2.79 Impact Factor
  • Source
    [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
  • [Show abstract] [Hide abstract]
    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