OXYSTEROL (7-BETA-HYDROXYCHOLESTERYL-3-OLEATE) PROMOTES SEROTONERGIC REINNERVATION IN THE LESIONED RAT SPINAL-CORD BY REDUCING GLIAL REACTION

In the present study, following previous experience with electrolytic lesion of the rat brain, and subsequent reduction of reactive gliosis with 7 beta-hydroxycholesterol derivatives (Bochelen et al.: Neuroscie nce 51:827-834, 1992), we have performed a hemisection of the spinal c ord in adult rats and investigated the influence of 7 beta-hydroxychor esteryl-3-oleate (oxysterol) on the intensity of the astrocytic reacti on and the axonal regeneration, We have shown here that local administ ration of liposomes containing this oxysterol reduced the intensity of the astroglial reaction on the sectioned side, as seen with immunocyt ochemical detection of glial fibrillary acidic protein (GFAP) and by i n situ hybridization with a specific RNA probe, Moreover, radioautogra phic evaluation of astrocyte proliferation with tritiated thymidine ev idenced a reduction of the astrocyte labelling index, In addition, dou ble immunocytochemical detection of GFAP and polysialylated neural cel l adhesion molecule (E-NCAM) revealed a decrease of the expression of this molecule in reactive astrocytes of the treated animals, Finally, immunocytochemical detection of serotonin (5HT) was determined in the raphespinal projections, which constitute a major descending system, I n treated animals, serotonergic axons originating from the intact side reinnervated the dorsal horn of the sectioned side, below the hemisec tion. These results demonstrate that 7 beta-hydroxycholesteryl-3-oleat e can reduce the astrocytic reaction following spinal cord injury, pro moting the serotonergic reinnervation of a denervated territory. (C) 1 995 Wiley-Liss, Inc.