Progesterone attenuates astro and microgliosis and decreases inflammatory reaction following spinal cord injury

LABOMBARDA, F; GONZALEZ, S; JURE, I; DE NICOLA A

Berlin

Congreso; 11th European Meeting on Glial Cells in Health and desease; 2013

Reactive gliosis and inflammatory mediators are implicated in demyelination and secondary damage after spinal cord injury (SCI). We have previously reported that after SCI, short-term progesterone treatment (3 days) stimulates oligodendrocyte precursor cells proliferation and decreases reactive gliosis, whereas chronic treatment (21 days) differenciates oligodendrocytes precursor cells into mature oligodendrocytes and enhances remyelination. Presently, we further studied whether progesterone was able to modulate the inflammatory reaction and cytokine production by astrocytes and microglial cells. Thus, the time-course mRNA expression of pro-inflammatory cytokines (IL1b, TNFa and IL-6) and pro-inflammatory enzymes (COX-2 and iNOS) was studied by PCR in Real Time.  Results showed that the highest increase in cytokine and pro-inflammatory enzymes mRNA production occurred in rat spinal cord 6 h after SCI. Progesterone treatment significantly decreased the early rise of proinflammatory mediators mRNAs at 6h. As progesterone action in spinal cord involves multiple mechanisms, the role played by the classical progesterone receptor (PR) on the progesterone inhibitory effects on cytokines, was assessed in PRKO mice. In agreement with data obtained in the rat model, SCI strongly stimulated TNFa, IL1b and IL-6 mRNA levels in spinal cord of both wild type and PRKO mice. However, whereas progesterone treatment inhibited the mRNAs of cytokines in wild type mice 6h after SCI, it was ineffective in PRKO mice, involving PR in the inhibition of cytokines production. Finally, we measured astrocyte and microglial cells density by immunohistochemsitry after 6 h of progesterone treatment. The steroid administration significantly decreases GFAP+ and Ox-42+ cells, which correlated with cytokine and pro-inflammatory enzymes inhibition. We conclude that progesterone attenuates reactive gliosis and inflammatory reaction, probably reducing the secondary spinal cord damage and favouring remyelination