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PO-0396 The Sigma-1 Receptor Agonist Pre-084 Protects Against Glutamate Induced Neurotoxicity In Primary Hippocampal Neurons
  1. E Griesmaier1,
  2. M Urbanek1,
  3. K Stock1,
  4. M Hermann2,
  5. A Posod1,
  6. RI Stanika3,
  7. GJ Obermair3,
  8. U Kiechl-Kohlendorfer1
  1. 1Paediatrics II Neonatology, Innsbruck Medical University, Innsbruck, Austria
  2. 2Anaesthesiology and Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria
  3. 3Physiology and Medical Physics, Innsbruck Medical University, Innsbruck, Austria

Abstract

Background Prematurity is a major determinant of neonatal mortality and morbidity. The number of preterm birth is still on the rise. Recently we and others could demonstrate neuroprotective effects of sigma-1 receptor ligands in adult and newborn animal models of brain injury. Since sigma-1 receptor agonists are already undergoing clinical trials in adult neurological disease, they might be considered a promising therapeutic option also in preterm brain injury. We have previously shown that the selective sigma-1 receptor agonist PRE-084 (2-(4-morpholinethyl)1-phenylcyclohexane-carboxylate) protects against neonatal excitotoxic brain injury in vivo . The aim of the present study was to investigate whether PRE-084 is able to prevent neurotoxicity following glutamate exposure in vitro .

Methods Cultured primary hippocampal neurons (day in vitro 10) were pre-treated with PRE-084 before glutamate was applied. Subsequently cell death was quantified by means of PI/calcein – AM staining using live confocal microscopy. Neurons were randomly assigned to one of the following groups: i) control, ii) glutamate or iii) glutamate+PRE-084. PRE-084 was applied in two dosages (10 and 100 µM) prior to glutamate.

Results The application of PRE-084 significantly reduced the percentage of dead cells (PRE-084 10 µM: 22.09 (20.50;28.84) and 100 µM: 25.87 (18.77;33.40)) compared to the untreated glutamate control group 43.56 (39,86;46.02).

Conclusion Our data show that administration of PRE-084 protects against glutamate induced cell death in primary hippocampal neurons. PRE-084 shows considerable promise as a therapeutic strategy in preterm brain injury and might provide an adequate means of combating this major cause of neurological disability in infancy.

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