Progesterone attenuates astro-and microgliosis and enhances oligodendrocyte differentiation following spinal cord injury

LABOMBARDA F.; GONZALEZ S.; LIMA A; ROIG P; GUENNOUN R.; SCHUMACHER M. ; DE NICOLA A.F.

EXPERIMENTAL NEUROLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2011 vol. 231 p. 135 - 146

0014-4886

Progesterone neuroprotection is partly due to neuronal effects and also by modulation of glial cell responses. Spinal cord injury (SCI) leads to pronounced changes of glial cell morphology and function, including development of astrogliosis, microglial activation and proliferation of NG2+ oligodendrocyte precursor cells. To elucidate the time effects of progesterone on these responses, we administered a short 3 day or a prolonged 21 day treatment with progesterone to rats with SCI. The number of S100b+ immature and mature astrocytes, GFAP+ mature astrocytes, OX-42+ microglia / macrophages and NG2+ cells was quantified by computerized morphometric analysis. Additionally, progesterone effects on proliferation /differentiation of glial cell types was studied by administration of two pulses of bromodeoxyuridine (BrdU) at 48 and 72 h post-injury, with rats killed 3 or 21 days post-injury. A strong stimulation of S100b+, GFAP+, OX-42 + cell density appeared at 3 and 21 days after spinal cord injury, which was significantly decreased at both time points in SCI rats treated with progesterone. In contrast, progesterone treatment increased NG2+ cells at 3 days but decreased them at 21 days. Double confocal immunofluorescence staining for colocalization of BrdU /GFAP, BrdU / S100b and BrdU / Ng2 was employed to determine effects on proliferation / differentiation of glial populations. Progesterone inhibited colocalization of BrdU with GFAP+ and S100b+ cells at 3 and 21 days, suggesting inhibition of astrocyte proliferation and differentiation. BrdU / NG2 colocalization was increased by progesterone at 3 days suggesting a proliferation stimulus, although the lack of BrdU+ / NG2+ cells at 21 days indicated progesterone-induced differentiation of precursors into NG2 negative phenotypes. We postulate that progesterone beneficial effects after SCI may involve: 1) inhibition of astrogliosis and of a potential glial scar; 2) anti-inflammatory effects by prevention of microglial activation, and 3) early time effects on proliferation with late differentiation of NG2+ cells to arouse remyelination.   .