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)
imidazole] on the morphology of astrocytes in the neonate and adult rat brain, and to explore the putative
neuroprotective effects of this glial response. 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 sections of facial motor nucleus from neonate rats processed for
glial fibrillary acidic protein (GFAP) immunostaining. Facial motoneurons surrounded by 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 mg kg(-1), i.p. every 12 h). Western-blot detection of the specific astroglial
glutamate transporter GLT-1, indicated increased immunoreactivity after
LSL 60101 treatment in the pons of neonate and in the parietoccipital cortex of adult rats. In the facial motor nucleus of neonate rats, the glial response after
LSL 60101 treatment was associated to a redistribution of the immunofluorescence 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. 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) significantly reduced (38%) motoneuron death rate 7 days after facial nerve
axotomy performed on day 3 after birth. It is concluded that treatment with the I(2)-imidazoline selective receptor
ligand LSL 60101 provokes morphological/biochemical changes in astroglia that are neuroprotective after neonatal
axotomy.