Progesterone inhibits inflammatory response pathways after permanent middle cerebral artery occlusion in rats

Abstract

Recent studies have indicated that progesterone (PROG) reduces the expression of inflammatory factors in brain tissue. The present study was designed to investigate whether PROG inhibits the inflammatory response and the inhltration of inflammatory cells in the brain. One hundred and seventy-six adult male Sprague-Dawley rats were randomly divided into four groups: a sham-operated (control) group, a permanent middle cerebral artery occlusion (pMCAO) group, a vehicle-treated group and a PROG-treated group. After pMCAO, the rats received an initial intraperitoneal injection of PROG (8 mg/kg) or vehicle at 1 h post-occlusion, followed by subcutaneous injections at 6, 24 and 48 h. The expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and CD68 in the brain were measured by immunohistochemistry and Western blotting. The level of myeloperoxidase (MPO) activity was detected by spectrophotometry. The rats were sacrificed 72 h after surgery and isolated brain was sectioned into coronal slices and stained with 2,3,5-triphenyltetrazolium chloride (TTC). Western blotting and spectrophotometry revealed that the expression levels of ICAM-1, VCAM-1, CD68 and MPO were reduced in the brain tissue of PROG-treated rats. In addition, PROG-treated rats showed a substantial reduction in the infarct volume compared to vehicle controls. PROG effectively inhibited the inflammatory response and reduced the inhltration of leukocytes in the ischemic brain by inhibiting the expression of ICAM-1 and VCAM-1.