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

Abstract

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 infiltration 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 infiltration of leukocytes in the ischemic brain by inhibiting the expression of ICAM-1 and VCAM-1.

Progesterone treatment reduces neuroinflammation, oxidative stress and brain damage and improves long-term outcomes in a rat model of repeated mild traumatic brain injury

“…These results of anti-inflammatory and anti-oxidant effects of PROG treatment in rmTBI are consistent with previous experiments in moderate to severe TBI studies [ 19 – 22 ]. Whilst the exact mechanisms remain unclear, PROG is thought to act on inflammation and oxidative stress both directly [ 47 , 48 ] and indirectly by the modulation of toll-like receptors and NF-κB signaling with a concurrent reduction in cytokines [ 49 , 50 ]. Nitric oxide has also been shown to be reduced by post-injury treatment with PROG, possibly through the prevention of inducible nitric oxide synthase, an isoform that abundantly produces nitric oxide during secondary injury [ 51 , 52 ].…”

Combination treatment with progesterone and vitamin D hormone is more effective than monotherapy in ischemic stroke: The role of BDNF/TrkB/Erk1/2 signaling in neuroprotection

“…P4 has been reported to exert anti-inflammatory effects in a variety of brain injury models (Cekic et al, 2011; Hua et al, 2011; Wang et al, 2011; Gibson et al, 2005). VDH also plays an important role in modulating inflammation under both normal and pathologic conditions (Balden et al, 2012; Kojima et al, 2012; Makariou et al, 2012; Sun et al, 2012).…”

The Serum Changes of Neuron-Specific Enolase and Intercellular Adhesion Molecule-1 in Patients With Diffuse Axonal Injury Following Progesterone Administration: A Randomized Clinical Trial

“…Also, progesterone decreased the inflammatory response and the leukocytes infiltration in the ischemic brain by inhibiting the expression of ICAM-1 (26). To the best of our knowledge, there has not yet been any contrary study assessing the effect of progesterone on ICAM-1 level in brain injury.…”