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 Blood was withdrawn at 6 hrs and 24 hrs after reperfusion, and ischemia was verified 24 hrs after reperfusion by MRI (magnetic resonance imaging) acquisition.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 (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. RezumatScopul studiului a fost evaluarea modificărilor în dinamică a 5 citokine, precum și corelația cu modificările imunohistochimice după ischemia indusă de ocluzia temporară a arterei cerebrale medii, la șobolanii cu și fără precondiționare cu ulei de pește. 30 șobolani masculi, adulți, rasa Wistar, randomizați în grupul control (n = 10), ischemic (n = 10) și cu administrare prealabilă de ulei de pește (FO) (n = 10), au fost supuși ischemiei cerebrale tranzitorii folosind tehnica minim invazivă cu monofilament intraluminal. Sângele a fost recoltat la 6 și la 24 ore după reperfuzie, iar controlul ischemiei s-a realizat imagistic la 24 ore. Evaluarea neurologică a fost făcută cu o scală de 5 puncte. Cinci citokine (TNF-alfa, IL6, TIMP-1, MCP-1 și VEGF) au fost analizate folosind tehnica multiplex bazată pe tehnologia xMAP. Concentrația plasmatică a TIMP-1 a fost mai mare la grupul ischemic și FO, comparativ cu grupul control la 6 ore după reperfuzie; în grupul ischemic concentrația TIMP-1 a crescut semnificativ după 24 ore (37,28 ± 4,85 pg/mL), comparativ cu grupul FO (14,11 ± 1,79 ng/mL), p < 0.0001. Nu au fost diferențe pentru concentrația plasmatică a MCP-1 între control (0,69 ± 0,18 pg/mL) și FO (0,798 ± 0,060 pg/mL), în schimb în grupul ischemic MCP-1 a fost ...

Fish-Oil Preconditioning Up-Regulates Expression of Splenic Arg1 Positive M2 Type Macrophages and the Arg1/Inos2 Ratio After Experimental Induced Transient Cerebral Ischemia

“…All rats were in good nutritional status (280 -330 g) and were divided by simple randomization into a sham group (S), salinetreated ischemic group (I), and highly purified fishoil (FO) phospholipid emulsion preconditioning group (T), with 10 animals each. Laboratory conditions and the treatment algorithm have been described in detail in our previous work [18]. In summary, T group specimens were treated daily with a phospholipid emulsion 21 days before tMCAO administered intraperitoneally in a dose of 3.5 mL/kg bw/day, corresponding to a concentration of 70 mg/kg bw eicosapentaenoic acid (EPA) and 80 mg/kg bw docosahexenoic acid (DHA).…”

“…Consecutively, prophylactic or therapeutic supplementation with n-3 PUFAs represents a highly promising neuroprotective strategy in a variety of neurological disorders. Based on our preliminary results regarding characterization of the inflammatory infiltrate in the damaged brain tissue and plasma cytokines profile after transient middle cerebral artery occlusion (tMCAO) [16,18], we hypothesized, that the degree of tissue injury in experimental cerebral ischemia can be associated by complex histopathological changes, not only in the brain but also in the spleen. In the current work, we focused on splenic responses in ischemia/reperfusion, splenic volume variation, and architectural changes.…”