uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: critical role of brain hyperthermia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. (Anaesthesiology and Intensive Care)
2007 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 26, no 5, 1242-1253 p.Article in journal (Refereed) Published
Abstract [en]

To clarify the role of brain temperature in permeability of the blood-brain barrier (BBB), rats were injected with methamphetamine (METH 9 mg/kg) at normal (23 °C) and warm (29 °C) environmental conditions and internal temperatures were monitored both centrally (nucleus accumbens, NAcc) and peripherally (skin and nonlocomotor muscle). Once NAcc temperatures peaked or reached 41.5 °C (a level suggesting possible lethality), animals were administered Evans blue dye (protein tracer that does not normally cross the BBB), rapidly anaesthetized, perfused and had their brains removed. All METH-treated animals showed brain and body hyperthermia associated with relative skin hypothermia, suggesting metabolic activation coupled with peripheral vasoconstriction. While METH-induced NAcc temperature elevation varied from 37.60 to 42.46 °C (or 1.2-5.1 °C above baseline), it was stronger at 29 °C (+4.13 °C) than 23 °C (+2.31 °C). Relative to control, METH-treated animals had significantly higher brain levels of water, Na+, K+ and Cl-, suggesting brain edema, and intense immunostaining for albumin, indicating breakdown of the BBB. METH-treated animals also showed strong immunoreactivity for glial fibrillary acidic protein (GFAP), possibly suggesting acute abnormality or damage of astrocytes. METH-induced changes in brain water, albumin and GFAP correlated linearly with NAcc temperature (r = 0.93, 0.98 and 0.98, respectively), suggesting a key role of brain hyperthermia in BBB permeability, development of brain edema and subsequent functional and structural neural abnormalities. Therefore, along with a direct destructive action on neural cells and functions, brain hyperthermia, via breakdown of the BBB, may be crucial for both decompensation of brain functions and cell injury following acute METH intoxication, possibly contributing to neurodegeneration resulting from chronic drug use.

Place, publisher, year, edition, pages
2007. Vol. 26, no 5, 1242-1253 p.
Keyword [en]
Albumin leakage, Astrocytic activation and damage, Brain water, Ions, Neurotoxicity, Rats
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-17224DOI: 10.1111/j.1460-9568.2007.05741.xISI: 000249130400016PubMedID: 17767502OAI: oai:DiVA.org:uu-17224DiVA: diva2:44995
Available from: 2008-06-18 Created: 2008-06-18 Last updated: 2011-01-26Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Sharma, Hari S.
By organisation
Department of Surgical Sciences
In the same journal
European Journal of Neuroscience
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 166 hits
ReferencesLink to record
Permanent link

Direct link