Exacerbation of Methamphetamine Neurotoxicity in Cold and Hot Environments: Neuroprotective Effects of an Antioxidant Compound H-290/51
2015 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, no 2, 1023-1033 p.Article in journal (Refereed) Published
In this study, we examined the influence of cold and hot environments on methamphetamine (METH) neurotoxicity in both drug-naive rats and animals previously exposed to different types of nanoparticles (NPs). Since METH induces oxidative stress, we also examined how a potential chain-breaking antioxidant H-290/51 (Astra-Zeneca, Molndal, Sweden) affects METH-induced neurotoxicity. Exposure of drug-naive rats to METH (9 mg/kg, s.c.) at 4, 21, or 34 A degrees C for 3 h resulted in breakdown of the blood-brain barrier (BBB), brain edema, and neuronal injuries, which all differed in severity depending upon ambient temperatures. The changes were moderate at 21 A degrees C, 120-180 % larger at 34 A degrees C, and almost absent at 4 A degrees C. In rats chronically treated with NPs (SiO2, Cu, or Ag; 50-60 nm, 50 mg/kg, i.p. for 7 days), METH-induced brain alterations showed a two- to fourfold increase at 21 A degrees C, a four- to sixfold increase at 34 A degrees C, and three- to fourfold increase at 4 A degrees C. SiO2 exposure showed the most pronounced METH-induced brain pathology at all temperatures followed by Ag and Cu NPs. Pretreatment with a potent antioxidant compound H-290/51 (50 mg/kg, p.o., 30 min before METH) significantly reduced brain pathology in naive animals exposed to METH at 21 and 34 A degrees C. In NPs-treated animals, however, attenuation of METH-induced brain pathology occurred only after repeated exposure of H-290/51 (-30 min, 0 min, and +30 min). These observations are the first to show that NPs exacerbate METH-induced brain pathology in both cold and hot environments and demonstrate that timely intervention with antioxidant H-290/51 could have neuroprotective effects.
Place, publisher, year, edition, pages
2015. Vol. 52, no 2, 1023-1033 p.
Methamphetamine, Ambient temperature, Nanoparticles, Cold environment, Hot environment, Blood-brain barrier, Brain edema, Neuronal injury, Antioxidants, H-290/51, Oxidative stress
Neurosciences Anesthesiology and Intensive Care
IdentifiersURN: urn:nbn:se:uu:diva-263423DOI: 10.1007/s12035-015-9252-9ISI: 000360687200021PubMedID: 26111626OAI: oai:DiVA.org:uu-263423DiVA: diva2:860659
FunderSwedish Research Council, 2710-HSSSwedish Foundation for Strategic Research Göran Gustafsson Foundation for Research in Natural Sciences and MedicineAstraZeneca