Progesterone attenuates astro and microgliosis and enhances oligodendrocyte differentittion following spinal cord injury

LABOMBARDA F; GONZALEZ S; GUENNOUN R; SCHUMACHER M; DE NICOLA A

Praga

Congreso; European Meeting on Glial Cells in Health and desease; 2011

Reactive gliosis, demyelination and proliferation of NG2+ oligodendrocyte precursor cells are common responses to spinal cord injury. We previously reported that short-term progesterone treatment stimulates oligodendrocyte precursor cells proliferation whereas chronic treatment enhances their differentiation after SCI. Presently, we further studied the proliferation /differentiation of glial cells involved in inflammation and remyelination in male rats with spinal cord injury subjected to acute (3 days) or chronic (21 days) progesterone administration. Rats received several pulses of bromodeoyuridine (BrdU) 48 and 72 h post-injury, and sacrificed 3 or 21 days post-injury. Double colocalization of BrdU and specific cell markers showed that 3 days of trauma induced a strong proliferation of S100 beta+ astrocytes, OX-42+ microglia / macrophages and NG2+ cells. At this stage, the intense GFAP+ astrogliosis was BrdU negative. Twenty one days of spinal cord injur enhanced maturation of S100 beta+ cells into GFAP+ astrocytes, but decreased the number of CC1+ oligodendrocytes. Progesterone treatment inhibited astrocyte and microglia /macrophage proliferation and activation in the 3-day injury group, and inhibited activation in the 21-day injury group. BrdU/NG2 double labelled cells were increased by progesterone at 3 days, indicating a proliferation stimulus, but decreased them at 21 days. However, progesterone- enhancement of CC1+/BrdU+ oligodendrocyte density, suggest differentiation of oligodendrocyte precursor cells into mature oligondendrocytes. We conclude that progesterone effects after spinal cord injury involves: a) inhibition of astrocyte proliferation and activation; b) anti-inflammatory effects by preventing microglial activation and proliferation, and c) early proliferation of NG2+ progenitors and late remyelination. Thus, progesterone behaves as a glioactive factor favouring remyelination and inhibiting reactive gliosis