title: Increase in activity of neutrophils and proinflammatory mediators in rats following acute and prolonged focal cerebral ischemia and reperfusion.
abstract: OBJECTIVE
  It has been proposed that the immune system is activated during ischemic cerebral events and that brain damage caused by ischemia is increased by this immune activity. Neutrophils (PMNs) are one of the first factors in the chain of reactions of the immune system during focal cerebral ischemia. Experimental and clinical studies have emphasized the important role of proinflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor (TNFalpha), in addition to vasoactive peptide and endothelin-1 (ET-1), in the formation of cerebral ischemia.
  
  
  METHODS
  The experiments were carried out using Wistar rats that were divided into four groups: three experimental groups (acute and prolonged focal cerebral ischemia and following reperfusion) and one control group (sham). Focal cerebral ischemia was induced by the intraluminal surgical suture method. The oxidative activity of PMNs was measured after stimulation with phorbol myristate acetate, a protein kinase C activator (luminol enhanced chemiluminescence). The concentration of IL-1beta and TNFalpha in rat lymphocyte culture after stimulation with CSF was determined using commercial ELISA kits. The plasma concentration of ET-1 was determined using commercial kits with the RIA method.
  
  
  RESULTS
  We confirmed a statistically significant increase in the oxidative activity of PMNs in rats with acute focal cerebral ischemia (p < 0.00001), prolonged ischemia (p < 0.001) and reperfusion (p < 0.05). An increase in IL-1beta and TNFalpha in lymphocytes following CSF stimulation was observed in the group with prolonged ischemia and in the group with reperfusion after transient ischemia (p < 0.05 for both). An increase in plasma ET-1 concentration was observed with acute and prolonged focal cerebral ischemia (p < 0.05 and p < 0.01, respectively).
  
  
  CONCLUSIONS
  Our results show that acute and prolonged focal cerebral ischemia and reperfusion induce statistically significant increases in the oxidative activity of PMNs. The concentration of proinflammatory mediators (IL-1beta, TNFalpha) as well as ET-1 is also increased, indicating the important role of immune reactions in the development of damage to the brain following ischemia.
authors.affiliation: Department of Neurosurgery, Medical University of Silesia, Katowice, Katowice, Poland. stanhendryk@interia.pl
authors.forename: Stanisław
authors.initials: S
authors.lastname: Hendryk
authors.forename: Zenon
authors.initials: Z
authors.lastname: Czuba
authors.forename: Halina
authors.initials: H
authors.lastname: Jedrzejewska-Szypułka
authors.forename: Piotr
authors.initials: P
authors.lastname: Bazowski
authors.forename: Hanna
authors.initials: H
authors.lastname: Dolezych
authors.forename: Wojciech
authors.initials: W
authors.lastname: Król
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D020536:Enzyme Activators / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D015424:Reperfusion; D018709:Statistics, Nonparametric; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D020536:Enzyme Activators; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D014660:Vasoactive Intestinal Peptide; D013755:Tetradecanoylphorbol Acetate