Fish-oil preconditioning modulates plasma MCP-1 and TIMP-1 levels after experimental induced transient cerebral ischemia

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 Blood was withdrawn at 6 hrs and 24 hrs after reperfusion, and ischemia was verified 24 hrs after reperfusion by MRI (magnetic resonance imaging) acquisition.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 (multi-analyte 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.