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Exacerbation of Methamphetamine Neurotoxicity in Cold and Hot Environments: Neuroprotective Effects of an Antioxidant Compound H-290/51
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
NIDA, Vivo Electrophysiol Unit, Behav Neurosci Branch, IRP,NIH, Baltimore, MD USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Univ Basque Country, Dept Neurosci, Bilbao, Spain..
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2015 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 52, no 2, 1023-1033 p.Article in journal (Refereed) Published
Abstract [en]

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.
Keyword [en]
Methamphetamine, Ambient temperature, Nanoparticles, Cold environment, Hot environment, Blood-brain barrier, Brain edema, Neuronal injury, Antioxidants, H-290/51, Oxidative stress
National Category
Neurosciences Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-263423DOI: 10.1007/s12035-015-9252-9ISI: 000360687200021PubMedID: 26111626OAI: oai:DiVA.org:uu-263423DiVA: diva2:860659
Funder
Swedish Research Council, 2710-HSSSwedish Foundation for Strategic Research Göran Gustafsson Foundation for Research in Natural Sciences and MedicineAstraZeneca
Available from: 2015-10-13 Created: 2015-09-30 Last updated: 2017-12-01Bibliographically approved

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Sharma, Hari ShankerSharma, Aruna

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