FISH-OIL PRECONDITIONING MODULATES PLASMA MCP-1 AND
TIMP-1 LEVELS AFTER EXPERIMENTAL INDUCED TRANSIENT
CEREBRAL ISCHEMIA
ADINA HUȚANU 1,2, EMOKE HORVATH 3, ALEX ORĂDAN 4, SEPTIMIU VOIDĂZAN 5 , LIVIU CHIRIAC 6, DANIELA LUCIA MUNTEAN 7*, MINODORA DOBREANU 1,2
1University of Medicine and Pharmacy of Târgu Mureș, Târgu Mureș, Romania
2Center for Advanced Medical and Pharmaceutical Research Târgu Mureș, Târgu Mureș, Romania
3Pathology Department, University of Medicine and Pharmacy, Târgu Mureș, Romania
4 “Iuliu Hațieganu” University of Medicine and Pharmacy, Center for Animal Facility, Cluj-Napoca, Romania,
5Department of Epidemiology, University of Medicine and Pharmacy Târgu Mureș, Romania
6National Magnetic Resonance Center, Faculty of Physics, Babeș-Bolyai University, Cluj-Napoca, Romania
7Department of Analytical Chemistry and Drug Analysis, University of Medicine and Pharmacy, Târgu Mureș, Romania
*corresponding author: danielaluciamuntean@yahoo.com
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Abstract:
The aim of the study was to assess the dynamic changes in cytokines profile and their correlation to immunohistochemistry
brain modifications after transient middle cerebral artery occlusion (tMCAO) in saline-treated ischemic rats compared to fish
oil preconditioned rats. 30 Wistar male adult rats randomly divided into sham (n = 10), ischemic (n = 10), and fish oil (FO) (n =
10) groups underwent tMCAO using a silicone monofilament technique with a minimum invasive procedure. Blood was
withdrawn at 6 hrs and 24 hrs after reperfusion, and ischemia was verified 24 hrs after reperfusion by MRI (magnetic
resonance imaging) acquisition. Neurological assessment was performed using a five-point scale. Five cytokines (TNF-alfa,
IL6, TIMP-1, MCP-1, and VEGF) were simultaneously analysed using the multiplex immunoassay based on xMAP (multianalyte
profiling) technology. Plasma concentration of TIMP-1 was higher in ischemic and FO group compared to sham, 6
hrs after reperfusion; in the ischemic group, the concentration of TIMP-1 raised significantly at 24 hrs (37.28 ± 4.85 pg/mL)
compared to FO group (14.11 ± 1.79 ng/mL), p < 0.0001. Plasma MCP-1 concentration did not differ between sham (0.69 ±
0.18 pg/mL) and FO group (0.798 ± 0.060 pg/mL), while in the ischemic group level was significantly higher (1.627 ± 0.19
pg/mL), p = 0.0001. Whilst in the ischemic group, concentrations were elevated at both points of measurement, in the FO
group the level significantly decreased after 24 hrs (p = 0.0005). Omega 3 PUFA (polyunsaturated fatty acid) decreased
plasma MCP-1 level, a key cytokine involved in the inflammatory cell migration. Additionally, in Omega 3 preconditioned
group, TIMP-1 expression was lower, probably due to a lower activation of matrix metalloproteinases.






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