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Rapid morphological brain abnormalities during acute methamphetamine intoxication in the rat: An experimental study using light and electron microscopy
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2009 (English)In: Journal of Chemical Neuroanatomy, ISSN 0891-0618, E-ISSN 1873-6300, Vol. 37, no 1, 18-32 p.Article in journal (Refereed) Published
Abstract [en]

This study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood-brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (i.v.) catheter were exposed to METH (9mg/kg) at standard (23 degrees C) and warm (29 degrees C) ambient temperatures, allowing for the observation of hyperthermia ranging from mild to pathological (38-42 degrees C). When brain temperature peaked or reached a level suggestive of possible lethality (>41.5 degrees C), rats were injected with Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) were analyzed for EB extravasation, water and electrolyte (Na(+), K(+), Cl(-)) contents, immunostained for albumin and glial fibrillary acidic protein (GFAP), and examined for neuronal, glial and axonal alterations using standard light and electron microscopy. These examinations revealed profound abnormalities in neuronal, glial, and endothelial cells, which were stronger with METH administered at 29 degrees C than 23 degrees C and tightly correlated with brain and body hyperthermia. These changes had some structural specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and serious shifts in brain ion homeostasis as leading factors underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration-the most dangerous complication of chronic amphetamine-like drug abuse.

Place, publisher, year, edition, pages
2009. Vol. 37, no 1, 18-32 p.
Keyword [en]
Blood-brain barrier, Brain edema, Brain pathology, Glial cells, Neuronal damage, Myelin vesiculation, Endothelial cells
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-88090DOI: 10.1016/j.jchemneu.2008.08.002ISI: 000262747500002PubMedID: 18773954OAI: oai:DiVA.org:uu-88090DiVA: diva2:134342
Available from: 2009-01-20 Created: 2009-01-20 Last updated: 2012-03-15Bibliographically approved

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Sharma, Hari Shanker
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