Induction of reactive astrocytosis and prevention of motoneuron cell deathby the I-2-imidazoline receptor ligand LSL 60101

1 I-2-imidazoline receptors are mainly expressed on glial cells in the rat brain. This study was designed to test the effect of treatment with the I-2 -imidazoline selective receptor ligand LSL 60101 [2-(2-benzofuranyl)imidazo le] on the morphology of astrocytes in the neonate and adult rat brain, and to explore the putative neuroprotective effects of this glial response. 2 Short-term (3 days) or chronic (7-10 days) treatment with LSL 60101 (1 mg kg(-1) i.p. every 12 h) enhanced the area covered by astroglial cells in s ections of facial motor nucleus from neonate rats processed for glial fibri llary acidic protein (GFAP) immunostaining. Facial motoneurons surrounded b y positive glial cell processes were frequently observed in sections of LSL 60101-treated rats. A similar glial response was observed in the parietal cortex of adult rats after chronic (10 days) treatment with LSL 60101 (10 m g kg-L, i.p. every 12 h). 3 Western-blot detection of the specific astroglial glutamate transporter G LT-1, indicated increased immunoreactivity after LSL 60101 treatment in the pens of neonate and in the parietoccipital cortex of adult rats. 4 In the facial motor nucleus of neonate rats, the glial response after LSL 60101 treatment was associated to a redistribution of the immunofluorescen ce of the basic fibroblast growth factor (FGF-2) from the perinuclear area of motoneurons to cover most of their cytoplasm, suggesting a translocation of this mitogenic and neurotrophic factor towards secretion pathways. 5 The neuroprotective potential of the above effects of LSL 60101 treatment was tested after neonatal axotomy of facial motor nucleus. Treatment with LSL 60101 (1 mg kg(-1), i.p. every 12 h from day 0 to day 10 after birth) s ignificantly reduced (38%) motoneuron death rate 7 days after facial nerve axotomy performed on day 3 after birth. 6 It is concluded that treatment with the I-2-imidazoline selective recepto r ligand LSL 60101 provokes morphological/biochemical changes in astroglia that are neuroprotective after neonatal axotomy.