Minireview Cell signaling in NMDA preconditioning and neuroprotection in convulsions induced by quinolinic acid Patricia Cardoso Severino a, ⁎, Gabriele do Amaral Silva Muller a , Samuel Vandresen-Filho b , Carla Inês Tasca b a Centro de Biologia Molecular e Estrutural Departamento de Bioquímica CCB, UFSC, Florianopolis, SC, CEP 88040-900 Brazil b Laboratório de Neuroquímica IV, Departamento de Bioquímica CCB, UFSC, Florianopolis, SC, CEP 88040-900 Brazil abstract article info Article history: Received 21 December 2010 Accepted 19 May 2011 Keywords: Preconditioning N-methyl-D-aspartate Neuroprotection Glutamatergic excitotoxicity Quinolinic acid NMDA receptor The search for novel, less invasive therapeutic strategies to treat neurodegenerative diseases has stimulated scientists to investigate the mechanisms involved in preconditioning. Preconditioning has been report to occur in many organs and tissues. In the brain, the modulation of glutamatergic transmission is an important and promising target to the use of effective neuroprotective agents. The glutamatergic excitotoxicity is a factor common to neurodegenerative diseases and acute events such as cerebral ischemia, traumatic brain injury and epilepsy. In this review we focus on the neuroprotection and preconditioning by chemical agents. Specially, chemical preconditioning models using N-methyl-D-aspartate (NMDA) pre-treatment, which has demonstrated to lead to neuroprotection against seizures and damage to neuronal tissue induced by quinolinic acid (QA). Here we attempted to gather important results obtained in the study of cellular and molecular mechanisms involved in NMDA preconditioning and neuroprotection. © 2011 Elsevier Inc. All rights reserved. Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 570 Preconditioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 571 Glutamatergic excitotoxicity and NMDA receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 571 NMDA preconditioning and neuroprotection against quinolinic acid (QA) insult . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 572 Adenosine receptors involved in NMDA preconditioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573 NMDA preconditioning and other insults . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574 Introduction Preconditioning was first identified in the canine heart when occlusion of the left circumflex coronary artery for 5 min applied four times produced tolerance against a 40 min occlusion. These brief periods of ischemia could reduce or prevent substantial damage caused by a subsequent, more prolonged ischemic episode, which was called preconditioning (Murry et al., 1986). The preconditioning, or induced tolerance, raised two important aspects: non-invasive methodology and the possibility to mimic cell protection through pharmacologically-based mechanisms (Stone, 2001; Stone and Addae, 2002; Loveridge and Schroeder, 2010). The general principle of preconditioning is to obtain a state of cell protection, tissue or whole organism through exposure to sub lethal insults that therefore grant certain tolerance to a subsequent lethal insult (Dirnagl et al., 2003; Mergenthaler et al., 2004; Zhang et al., 2010; Costa et al., 2010). The preconditioning mechanism was not limited to the heart but existed in neural tissue also. Neuroprotection and brain repair after acute brain damage still major goals for the scientific community. The mechanisms by which the brain protects itself against insults and recovers from damage are being studied and a comprehensive Life Sciences 89 (2011) 570–576 ⁎ Corresponding author at: Centro de Biologia Molecular e Estrutural, Departamento de Bioquímica, CCB, UFSC, Trindade, 88040-900 Florianópolis, SC, Brazil. Tel.: + 55 48 3721 6426; fax: +55 48 37211 9672. E-mail addresses: patsics@gmail.com, patsi@brturbo.com.br (P.C. Severino). 0024-3205/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2011.05.014 Contents lists available at ScienceDirect Life Sciences journal homepage: www.elsevier.com/locate/lifescie