Effects of intrathecal administration of IL-6 antagonist on ultrastructural changes after experimental MCA occlusion in the rat examination with electron microscopy

Brain ischemia triggers a complex cascade of secondary injury mechanisms. Identified mechanisms of post ischemic neuronal injury include altered Ca 2' homeostasis, free radical formation, mitochondrial dysfunction, protease activation, altered gene expression, and inflammation. Cytokines are recognized mediators of inflammatory responses. Interleukin-6 (IL-6), which is one of the main inflammation-associated cytokines. Although IL-6 levels increase after brain ischemia, study results have conflicted with regard to whether this increased IL-6 exerts neuroprotective or neurotoxic effects. The aim of this study was to analyze the relationship between neutralization of IL-6 bioactivity and late phase electron microscopic findings of brain ischemic injury in a rat model of middle cerebral artery occlusion. Forty male Wistar rats weighing ?.80 to 310 g were used in this study. The animals were randomly allocated in four groups; control (group 1), sham-operated (group 2), occlusion (group 3) and IL-6 anti-rat anibody treated groups (group 4). Group 4 received one intrathecal injection of 5u,g IL-6 anti-rat antibody immediately after occlusion. In group 4, the 10 rats that were sacrificed on 1 week post -occlusion received one dose. The sample from the ischemic core was collected. Results of this group were compared with other groups electron microscopic findings. Electron microscopy revealed marked structural changes in the brains of the occlusion group. However, group 4 showed milder cellular and subcellular damage, and less edema. Our clinical findings suggest an important role neutralization of rat IL-6 bioactivity reduces of secondary damage, in long-term recovery for after permanent focal central nervous system ischemia in the rat.Key Words: Rat, cerebral, ischemia, interleukin-6, electron microscope