CONICET | Buscador de Institutos y Recursos Humanos

Remyelinating effects of progesterone (PROG) after spinal cord injury (SCI) F Labombarda 1, 2 , S González 1, 2, A Lima 1, P Roig 1, R Guennoun 3, M Schumacher 3 and AF. De Nicola 1,2 * 1 Laboratory of Neuroendocrine Biochemistry, Instituto de Biologia y Medicina Experimental-CONICET, Buenos Aires, Argentina. 2 Dept. of Human Biochemistry, Faculty of Medicine, University of Buenos Aires, Buenos Aires, Argentina. 3 UMR788 Inserm and University Paris 11, Kremlin-Bicêtre, France PROG is emerging as a myelinizing factor for CNS injury. Remyelination requires proliferation and differentiation of oligodendrocyte precursor cells into myelinating oligodendrocytes (OL), but this process is incomplete following injury. To study progesterone actions on remyelination, we administered PROG (16 mg/kg/day) to rats with complete SCI for 21 days. To determine if cells which divided at 2 and 3 days after injury differentiated into mature OL (CC1+ cells), bromodeoxyuridine (BrdU, 200mg/kg ip) was given each day during 48 and 72 h after lesion. These animals were euthanized 18 days after the last BrdU injection and processed for double labeling (BrdU-CC1). The number of positive cells was counted in a fixed area (50.000 mm2) of white matter below the lesion. The number of OL decreased in SCI group (39.67±7.17 vs CTL: 75.09±8.78 p<0.01) while PROG restored them (78.60±7.13, p<0.001). The fact that 45% of CC1 cells in SCI+PROG was also BrdU+, indicated they were newly differentiated OL. Thus, PROG restored the number of CC1+ cells, promoting the differentiation of cells which divided at 2 or 3 days after injury. In control and SCI only 6-8 % of CC1 cells were double labeled indicating a poor differentiation. Thus, PROG effects on oligodendrogenesis may constitute a fundamental step to repair traumatic injury inflicted to the spinal cord Supported by PIP 5542, MO22 UBA, INSERM / CONICET Agreement and FONCYT PICT 5-08663 and PICT 00291