An 18-mer peptide fragment of prosaposin ameliorates place navigation disability, cortical infarction, and retrograde thalamic degeneration in rats with focal cerebral ischemia

It was previously reported that prosaposin possesses neurotrophic activity that:is ascribed to an 18-mer peptide comprising the hydrophilic sequence o f the rat saposin C domain. To evaluate the effect of the 18-mer peptide on ischemic neuronal damage, the peptide was infused in the left lateral vent ricle immediately after occlusion of the left middle cerebral artery (MCA) in stroke-prone spontaneously hypertensive (SP-SH) rats. The treatment amel iorated the ischemia-induced space navigation disability and cortical infar ction and prevented secondary thalamic degeneration in a dose-dependent man ner. In culture experiments, treatment with the 18-mer peptide attenuated f ree radical-induced neuronal injury at low concentrations (0.002 to 2 pg/mL ), and the peptide at higher Concentrations (0.2 to 20 ng/mL) protected neu rons against hypoxic insult. Furthermore, a saposin C fragment comprising t he 18-mer peptide bound to synaptosomal fractions of the cerebral cortex, a nd this binding decreased at the Ist day after MCA occlusion and recovered to the preischemic level at the 7th day after ischemia. These findings sugg est that the 18-mer peptide ameliorates neuronal damage in vivo and in vitr o through binding to the functional receptor, although the cDNA encoding pr osaposin receptor has not been determined yet.