Mild hypothermia causes differential, time-dependent changes in cytokine expression and gliosis following endothelin-1-induced transient focal cerebral ischemia

Journal of Neuroinflammation

Yvette Michotte¹  Sophie Sarre¹  Said Hachimi-Idrissi²  Ron Kooijman³  Tine Zgavc¹  An-Gaëlle Ceulemans¹ 

[1] Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium;Critical Care Department and Cerebral Resuscitation Research Group, Center for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium;Department of Pharmacology, Center for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, 1090, Belgium

关键词: Gliosis;    Cytokines;    Neuroinflammation;    Hypothermia;    Stroke;   

Others  :  1213321
DOI  :  10.1186/1742-2094-8-60

 received in 2011-01-24, accepted in 2011-05-31,  发布年份 2011

【 摘 要 】

Background

Stroke is an important cause of morbidity and mortality and few therapies exist thus far. Mild hypothermia (33°C) is a promising neuroprotective strategy to improve outcome after ischemic stroke. However, its complete mechanism of action has not yet been fully elaborated. This study is the first to investigate whether this neuroprotection occurs through modulation of the neuroinflammatory response after stroke in a time-dependent manner.

Methods

The Endothelin-1 (Et-1) model was used to elicit a transient focal cerebral ischemia in male Wistar rats. In this model, the core and penumbra of the insult are represented by the striatum and the cortex respectively. We assessed the effects of 2 hours of hypothermia, started 20 minutes after Et-1 injection on neurological outcome and infarct volume. Furthermore, pro- and anti-inflammatory cytokine expression was determined using ELISA. Microgliosis and astrogliosis were investigated using CD-68 and GFAP staining respectively. All parameters were determined 8, 24, 72 hours and 1 week after the administration of Et-1.

Results

Et-1 infusion caused neurological deficit and a reproducible infarct size which increased up to 3 days after the insult. Both parameters were significantly reduced by hypothermia. The strongest reduction in infarct volume with hypothermia, at 3 days, corresponded with increased microglial activation. Reducing the brain temperature affected the stroke induced increase in interleukin-1β and tumor necrosis factor α in the striatum, 8 hours after its induction, but not at later time points. Transforming growth factor β increased as a function of time after the Et-1-induced insult and was not influenced by cooling. Hypothermia reduced astrogliosis at 1 and 3 days after stroke onset.

Conclusions

The beneficial effects of hypothermia after stroke on infarct volume and functional outcome coincide with a time-dependent modulation of the cytokine expression and gliosis.

【 授权许可】

   
2011 Ceulemans et al; licensee BioMed Central Ltd.

【 图 表 】

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