Multilayer polyion complex nanoformulations of superoxide dismutase 1 for acute spinal cord injury.

As one of the most devastating forms of trauma, spinal cord injury (SCI) remains a challenging clinical problem. The secondary processes associated with the primary injury, such as overproduction of reactive oxygen species (ROS) and inflammation, lead to concomitant compression of the injured spinal cord and neuronal death. Delivery of copper-zinc superoxide dismutase (SOD1), an efficient ROS scavenger, to the site of injury can mitigate SCI-induced oxidative stress and tissue damage. Towards this goal catalytically active nanoformulations of SOD1 ("nanozymes") are developed as a modality for treatment of SCI. Along with the cross-linked polyion complex of SOD1 with polycation poly(ethylene glycol) (PEG)-polylysine (single-coat (SC) nanozyme), we introduce for the first time the chemically cross-linked multilayer polyion complex in which SOD1 is first incorporated into a polyion complex with polycation, then coated by anionic block copolymer, PEG-polyglutamic acid (double-coat (DC) nanozyme). We developed DC nanozymes with high enzymatic activity and ability to retain and protect SOD1 under physiological conditions. Pharmacokinetic study revealed that DC nanozymes significantly prolonged circulation of active SOD1 in the blood stream compared to free SOD1 or SC nanozymes (half-life was 60 vs 6min). Single intravenous injection of DC nanozymes (5kU of SOD1/kg) improved the recovery of locomotor functions in rats with moderate SCI, along with reduction of swelling, concomitant compression of the spinal cord and formation of post-traumatic cysts. Thus, based on the testing in a rodent model the SOD1 DC nanozymes are promising modality for scavenging ROS, decreasing inflammation and edema, and improving recovery after SCI.

Effect of Electroconvulsive Therapy on Cognitive Functions of Rats with Depression-Like Disorders Induced by Ultrasound Exposure.

We studied the effect of electroconvulsive therapy on cognitive functions in rats with depression-like disorder caused by exposure to ultrasound of varying frequency (20-45 kHz). Object recognition and Morris water-maze tests revealed no negative effects of the therapy on memory. Moreover, positive effect of therapy was demonstrated that manifested in amelioration of memory disturbances in depression-like disorders in these behavioral tests. The results of this study do not support the idea about side effects of electroconvulsive therapy, in particular, development of transient amnesia, and are a prerequisite for a more thorough study of internal mechanisms of the effect of the therapy on cognitive sphere.

[Behavioral Phenotype of Mice with Alkali Sensor IRR Gene Knockout].

Receptor-like tyrosine kinase IRR (the insulin receptor-related receptor) can be activated by extra- cellular alkaline media. IRR is found in organs that come in contact with liquids of extremal pH, and also in specific cells of the nervous systems where its function is not known. In this study, we analyzed the phenotype of IRR knockout mice in a series of behavioral tests. In control experi- ments, null-mutation littermate mice were analyzed. In the "Social interaction" test, the knockout animals showed a reduced number of social contacts. No statistically significant differences in im- mobility time were revealed in the "Forced swim" test, yet the number of animals that showed pro- longed immobility time, was higher in the group of knockout mice. In the "Resident-intruder" test, wild-type mice demonstrated their typical aggressive behavior whereas 7 out of 16 knockout animals stayed inert and, in contrast, attacked by the intruder. The obtained data suggest that the IRR gene inactivation results in disturbances of the aggressive-defensive behavior typical of the parental mouse strain.