The effects of enriched environment on the behavioral and corticosterone response to methamphetamine in adolescent and adult mice.

Methamphetamine alters behavior and the stress response system. Relatively little research has examined the effects of methamphetamine in adolescents and compared these effects to those in adults. Housing in enriched environments has been explored as one way to protect against the effects of methamphetamine, but the findings are conflicting and no study has examined how enriched environment may alter the behavioral and corticosterone responses to methamphetamine in adolescent and adult rodents. We examined the long-term effects of methamphetamine exposure on anxiety, social behavior, behavioral despair, and corticosterone levels in adolescent and adult mice housed in enriched or isolated environments. Enriched environment did not alter the behavioral or corticosterone response to methamphetamine. Methamphetamine exposure decreased anxiety and increased behavioral despair in adult mice, but methamphetamine did not alter behavior in adolescent mice. There was no effect of methamphetamine on social behavior or corticosterone levels. Our findings demonstrate that the specific environmental enrichment paradigm used in this study was not sufficient to mitigate the behavioral effects of methamphetamine and that adolescent mice are relatively resistant to the effects of methamphetamine compared to adult mice.

Vitrification and Rewarming of Magnetic Nanoparticle-Loaded Rat Hearts.

To extend the preservation of donor hearts beyond the current 4-6 h, this paper explores heart cryopreservation by vitrification-cryogenic storage in a glass-like state. While organ vitrification is made possible by using cryoprotective agents (CPA) that inhibit ice during cooling, failure occurs during convective rewarming due to slow and non-uniform rewarming which causes ice crystallization and/or cracking. Here an alternative, "nanowarming", which uses silica-coated iron oxide nanoparticles (sIONPs) perfusion loaded through the vasculature is explored, that allows a radiofrequency coil to rewarm the organ quickly and uniformly to avoid convective failures. Nanowarming has been applied to cells and tissues, and a proof of principle study suggests it is possible in the heart, but proper physical and biological characterization especially in organs is still lacking. Here, using a rat heart model, controlled machine perfusion loading and unloading of CPA and sIONPs, cooling to a vitrified state, and fast and uniform nanowarming without crystallization or cracking is demonstrated. Further, nanowarmed hearts maintain histologic appearance and endothelial integrity superior to convective rewarming and indistinguishable from CPA load/unload control hearts while showing some promising organ-level (electrical) functional activity. This work demonstrates physically successful heart vitrification and nanowarming and that biological outcomes can be expected to improve by reducing or eliminating CPA toxicity during loading and unloading.

Vitrification and Nanowarming of Kidneys.

Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled "nanowarming" addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica-coated iron oxide nanoparticles (sIONPs). After cooling at -40 °C min-1 in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min-1 . Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation.