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Expression of heat shock protein (HSP 72 kDa) during acute methamphetamine intoxication depends on brain hyperthermia: neurotoxicity or neuroprotection?
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2011 (English)In: Journal of neural transmission, ISSN 0300-9564, E-ISSN 1435-1463, Vol. 118, no 1, 47-60 p.Article in journal (Refereed) Published
Abstract [en]

In the present study, light and electron microscopy were used to examine heat shock protein (HSP 72kD) expression during acute methamphetamine (METH) intoxication in rats and evaluate its relationships with brain temperature and alterations in a number of other histochemical and morphological parameters. Freely moving rats received METH at the same dose (9 mg/kg, sc) but at different ambient temperatures (23 and 29°C), showing a wide range of brain temperature elevations (37.6-42.5°C); brains were taken for histochemical and morphological evaluations at peak of brain temperature increase. We found that acute METH intoxication induces massive and wide-spread HSP expression in neural and glial cells examined in detail in the cortex, hippocampus, thalamus, and hypothalamus. In each of these structures, the number of HSP-positive cells tightly correlated with brain temperature elevation. The changes in HSP immunoreactivity were also tightly related to alterations in permeability of the blood-brain barrier, acute glial activation, and brain edema assessed by albumin and GFAP immunoreactivity and measuring tissue water content, respectively. While robust and generalized HSP production normally appears to be the part of an adaptive brain response associated with METH-induced metabolic activation, activation of this protective mechanism has its natural limits and could not counteract the damaging effects of oxidative stress, high temperature, and edema-the leading factors of METH-induced neurotoxicity.

Place, publisher, year, edition, pages
2011. Vol. 118, no 1, 47-60 p.
Keyword [en]
Blood-brain barrier, Brain hyperthermia, Edema, Metabolic activation, Neural and glial cells, Oxidative stress, Rats
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-139830DOI: 10.1007/s00702-010-0477-5ISI: 000286605700006PubMedID: 20931246OAI: oai:DiVA.org:uu-139830DiVA: diva2:382163
Available from: 2010-12-30 Created: 2010-12-30 Last updated: 2012-03-15Bibliographically approved

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Sharma, Hari S.
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