• B P Brown, S C Kang, K Gawelek, R A Zacharias, S R Anderson, C P Turner, and J K Morris.
• Neuroscience Program, Baldwin Wallace University, Berea, OH 44017, USA; Department of Chemistry, Baldwin Wallace University, Berea, OH 44017, USA.
• Neuroscience. 2015 Apr 2;290:31-40.

AbstractAnesthetic doses of ketamine induce apoptosis, as well as gene expression of activity-dependent neuroprotective protein (ADNP), a putative homeodomain transcription factor in rat pups (P7). This study investigated if ketamine induced ADNP protein in a dose-dependent manner in vitro and in vivo using primary cultures of cortical neurons and neonatal pups (P7). In vivo immunohistochemistry demonstrated a sub-anesthetic dose of ketamine increased ADNP in the somatosensory cortex (SCC) which was previously identified to be damaged by repeated exposure to anesthetic doses of ketamine. Administration of low-dose ketamine prior to full sedation prevented caspase-3 activation in the hippocampus and SCC. Primary cultures of cortical neurons treated with ketamine (10 μM-10mM) at 3 days-in vitro (3 DIV) displayed a concentration-dependent decrease in expanded growth cones. Furthermore, neuronal production and localization of ADNP varied as a function of both ketamine concentration and length of exposure. Taken together, these data support the model that ADNP induction may be partially responsible for the efficacy of a low-dose ketamine pre-treatment in preventing ketamine-induced neuronal cell death.Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

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