Summary: It has been demonstrated that administration of an interleukin-l receptor antagonist protein (IL-lra) reduces isch emic brain injury; however, the detrimental mechanism initi ated by interleukin-l (IL-I) in ischemic brain injury is unclear, In this study, we used mice that were transfected to overexpress human IL-lra to elucidate the role of IL-I in the activation of the inflammatory response after middle cerebral artery occlu sion (MeAO), Myeloperoxidase (MPO) activity and immuno histostaining were used as a marker of polymorphonuclear leu kocytes (PMNL) infiltration, Adenoviral vector (l x 10 9 par ticles) was administered by injection into the right lateral ventricle in mice, Five days later, MeAO was performed on the mice using a suture technique, Permanent MeAO was achieved for 24 hours in the Ad,RSY IL-/ ra-transfected, Ad,RSY lacZ transfected, and saline (control) mice, Myeloperoxidase activ ity was quantified in each region and localization of MPO was determined by immunohistochemistry, After 2 hours of MeAO, the surface cerebral blood flow was reduced to 13,5% ± 3A%, 10,75% ± 2.6%, and \0,9% ± 2.6% of baseline in the ischemic hemisphere in Ad.RSV lL-l ra-transfected, Ad.RSVPolymorphonuclear leukocytes (PMNL) have been proposed to contribute to the pathogenesis of cerebral ischemia and stroke since the late 1960s (Somas et aI., 1972). Delayed accumulation of PMNL and monocytes
840lacZ-transfected, and saline-treated mice, respectively, The MPO activity in the ischemic hemisphere in the Ad,RSVlacZ group was similar to that in the saline control group (cortex: OAO ± 0.22 versus 0,33 ± 0. 11; basal ganglia: OA6 ± 0.23 versus OA9 ± 0,17; P > 0.05); however, it was significantly reduced in the Ad.RSV IL-l ra group (cortex: 0.18 ± 0.07; basal ganglia: 0.26 ± 0.15; P < 0.05). Myeloperoxidase immunohis tochemistry showed that the massive accumulation of MPO positive cells in the ischemic cortex, striatum, and corpus cal losum regions was greatly attenuated in Ad,RSYIL-Jra transfected mice, Our results indicate that Ad.RSY lL-1 ra transfected mice provide a useful tool to study the mechanism of action of IL-I. The MPO activity assay and immunostaining after 24 hours of focal ischemia were significantly reduced in IL-I ra gene-transfected mice, suggesting that IL-I may play an important role in the activation of inflammatory cells during focal cerebral ischemia. Key Words: lmmunohistochemis try-Ischemia-Mice-Middle cerebral artery occlusion Myeloperoxidase-Neutrophil. after experimental stroke was demonstrated in 1974 (Garcia and Kamijyo, 1974). Using indium-Ill-labeled autologous PMNL in a model of air embolism-induced cerebral ischemia in dogs, Hallenbeck et al. (1986) con firmed that PMNL accumulate progressively during the first 4 hours of reperfusion. Much of the research litera ture has demonstrated that brain injury caused by isch emia and reperfusion can be attenuated by PMNL deple tion (del Zoppo et aI., 1991; Dutka et aI., 1989; Shiga et aI., 1991), Schurer et al. (1990) showed that antine...