Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, which is characterized by anxiety- and depression-like behaviors and cognitive impairment. However, the underlying mechanisms remain elusive. Parvalbumin (PV) interneurons that are susceptible to oxidative stress are a subset of inhibitory GABAergic neurons regulating the excitability of pyramidal neurons, while dysfunction of PV interneurons is casually linked to many mental disorders including PTSD. We therefore hypothesized that environmental enrichment (EE), a method of enhanced cognitive, sensory and motor stimulation, can reverse the behavioral impairments by normalizing PV interneurons in a rat model of PTSD induced by inescapable foot shocks (IFS). Behavioral changes were determined by the open field, elevated plus maze, fear conditioning, and Morris water maze tests. The levels of nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NOX4, PV, glutamic acid decarboxylase 67 (GAD-67), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in the hippocampus and prefrontal cortex were determined. Our results showed that in this PTSD model, rats displayed the anxiety-like behavior, enhanced fear learning behavior, and hippocampus- dependent spatial memory deficit, which were accompanied by the up-regulation of NOX2, 8-OH-dG, and down-regulation of PV and GAD-67. Notably, EE reversed all these abnormalities. These results suggest that restoration of PV interneurons by inhibiting oxidative stress in the hippocampus and prefrontal cortex might represent a mechanism through which EE reverses the behavioral impairments in a rat model of PTSD induced by IFS.

The activation of adenosine monophosphate-activated protein kinase in rat hippocampus contributes to the rapid antidepressant effect of ketamine.

Recent studies have shown a rapid, robust, and lasting antidepressant effect of ketamine that makes ketamine a promising antidepressant drug. However, the mechanisms underlying this rapid antidepressant effect remain incompletely understood. The goal of the present study was to determine whether adenosine monophosphate-activated protein kinase (AMPK) was involved in ketamine's rapid antidepressant effect during the forced swimming test (FST). In the first stage of experiment, a lower level of phosphorylated form of AMPK (p-AMPK) in the hippocampus and a longer immobility time were observed in the depressed rats during FST; whereas ketamine reversed these changes at 30min after the administration. In the second stage of experiment, we observed that, ketamine up-regulated the levels of p-AMPK and brain-derived neurotrophic factor (BDNF) in the hippocampus of the depressed rats. Moreover, AMPK agonist strengthened the antidepressant effect of ketamine with an up-regulation of BDNF, while AMPK antagonist attenuated the antidepressant effect of ketamine with a down-regulation of BDNF. In conclusion, our results suggest that the activation of AMPK in rat hippocampus is involved in the procedure of ketamine exerting rapid antidepressant effect through the up-regulation of BDNF.

Misplacement of LVAD inflow cannula leads to insufficient output and tissue hypoperfusion.

A 63-year-old man with a newly placed left ventricular assist device (LVAD) was emergently taken to the operating room for mediastinal exploration secondary to worsened LVAD output, hemodynamic instability, and organ hypoperfusion. Intraoperative transesophageal echocardiography showed the LVAD inflow cannula intermittently aspirating the atrial septal wall, resulting in occlusion of the inflow cannula. Upon gradual withdrawal of the inflow cannula by several centimeters, dramatic improvements in LVAD output, hemodynamics, and tissue perfusion occurred. Clinical implications of a patient who has a malfunctioning LVAD are discussed.