Combined Estrogen and Progesterone Effect on Inflammatory Cytokines Gene Expression and Lymphocyte Migration to Penumbra Region after Ischemic Stroke Model in Rat

Ischemic stroke is the most leading cause of death and long-term disability due to middle cerebral artery occlusion, which result in inflammation process in the affected area of the brain. Although many attempts have been made to treat stroke, therapeuticmodalities to fight stroke are still limited.However, mounting evidence have documented that estrogen and progesterone hormones have neuroprotective effects. In the present study the effect of combined dose of estrogen and progesterone on gene expression level ofinflammation cytokine including TNF-a, IL-6 and IL-1B as well as the migration of lymphocytes to the marginal region, in the MCAO model have been investigated. Materials and Methods: In this study, 40 adult male Wistar rats were kept in a controlled environment andthen randomly divided into three groups: ischemia, hormone and sham. The MCAO model was performed within 1 h and estrogen and progesterone combination were immediately injected after MCAO subcutaneously. TTC staining was used for measurement of infarctvolume. Moreover, IHC technique carried out in order to evaluate lymphocyte migration rate to pneumobra region. Besides, real-time PCR and western blot analysis was used to explore gene and protein expression level of TNF-α،IL-1β and IL-6 respectively. P value lessthan 0.5 was statically considered significant. Results: Combination of estrogen (25 μg/kg) and progesterone (10 mg/kg) injected immediately after focal ischemia could significantly reduce lesion volume, migration of CD4 +lymphocytes to pneumobra region and thus reducedinflammation. It also significantly increased the score of behavioral tests. Conclusion: The results of this study proved the anti-inflammatory effect of combined dose of estrogen and progesterone. Furthermore, the findings indicated such combination significantly reducesinflammation and migration of CD4 +lymphocytes to pneumobra region after MCAO