Spontaneously hypertensive rats display reduced microglial activation in response to ischemic stroke and lipopolysaccharide

Journal of Neuroinflammation

Ron Kooijman¹  Jacques De Keyser²  Yvette Michotte³  Sophie Sarre³  Tine Zgavc³  Wendy Stoop¹  Deborah De Geyter¹ 

[1] Department of Pharmacology, Center for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium;Department of Neurology, University Medical Center Groningen, Groningen, The Netherlands;Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neuroscience, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium

关键词: Blood flow;    Glial cells;    Hypertension;    Endothelin-1;    Focal cerebral ischemia;   

Others  :  1212561
DOI  :  10.1186/1742-2094-9-114

 received in 2011-08-23, accepted in 2012-05-30,  发布年份 2012

【 摘 要 】

Background

For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals.

Methods

The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein.

Results and conclusions

The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24 h after the insult. However, both differences disappeared between 24 and 72 h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria.

【 授权许可】

   
2012 De Geyter et al.; licensee BioMed Central Ltd.

【 图 表 】

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