Biochemical and inflammatory biomarkers in ischemic stroke: translational study between humans and two experimental rat models

Journal of Translational Medicine

Exuperio Díez-Tejedor¹  Maria Elena Novillo-López²  María Alonso de Leciñana Cases²  Jaime Masjuán²  Blanca Fuentes¹  María Gutiérrez-Fernández¹  Patricia Martínez-Sánchez¹ 

[1] Department of Neurology and Stroke Center, Neuroscience and Cerebrovascular Research Laboratory, La Paz University Hospital, Autonoma of Madrid University, Neurosciences Area of IdiPAZ Health Research Institute, Alcalá de Henares University, Madrid, Spain;Department of Neurology, Stroke Unit, Ramón y Cajal Hospital, IRYCIS Health Research Institute, Madrid, Spain

关键词: Inflammation;    Cell death;    Acute stroke;    Animal models;    Chemokines;    Brain ischemia;   

Others  :  1148591
DOI  :  10.1186/s12967-014-0220-3

 received in 2014-03-08, accepted in 2014-07-23,  发布年份 2014

【 摘 要 】

Background

our objective was to examine the plasma levels of three biological markers involved in cerebral ischemia (IL-6, glutamate and TNF-alpha) in stroke patients and compare them with two different rat models of focal ischemia (embolic stroke model- ES and permanent middle cerebral artery occlusion ligation model-pMCAO) to evaluate which model is most similar to humans. Secondary objectives: 1) to analyze the relationship of these biological markers with the severity, volume and outcome of the brain infarction in humans and the two stroke models; and 2) to study whether the three biomarkers are also increased in response to damage in organs other than the central nervous system, both in humans and in rats.

Methods

Multi-center, prospective, case-control study including acute stroke patients (n = 58) and controls (n = 19) with acute non-neurological diseases Main variables: plasma biomarker levels on admission and at 72 h; stroke severity (NIHSS scale) and clinical severity (APACHE II scale); stroke volume; functional status at 3 months (modified Rankin Scale [mRS] and Barthel index [BI]). Experimental groups: ES (n = 10), pMCAO (n = 6) and controls (tissue stress by leg compression) (n = 6). Main variables: plasma biomarker levels at 3 and 72 h; volume of ischemic lesion (H&E) and cell death (TUNEL).

Results

in stroke patients, IL-6 correlated significantly with clinical severity (APACHE II scale), stroke severity (NIHSS scale), infarct volume (cm³) and clinical outcome (mRS) (r = 0.326, 0.497, 0.290 and 0.444 respectively; P < 0.05). Glutamate correlated with stroke severity, but not with outcome, and TNF-alpha levels with infarct volume. In animals, The ES model showed larger infarct volumes (median 58.6% vs. 29%, P < 0.001) and higher inflammatory biomarkers levels than pMCAO, except for serum glutamate levels which were higher in pMCAO. The ES showed correlations between the biomarkers and cell death (r = 0.928 for IL-6; P < 0.001; r = 0.765 for TNF-alpha, P < 0.1; r = 0.783 for Glutamate, P < 0.1) and infarct volume (r = 0.943 for IL-6, P < 0.0001) more similar to humans than pMCAO. IL-6, glutamate and TNF-α levels were not higher in cerebral ischemia than in controls.

Conclusions

Both models, ES and pMCAO, show differences that should be considered when conducting translational studies. IL-6, Glutamate and TNF-α are not specific for cerebral ischemia either in humans or in rats.

【 授权许可】

   
2014 Martinez-Sanchez et al.; licensee BioMed Central Ltd.

【 图 表 】

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Figure 3.

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