Abstract: Objective To investigate neurotoxic effects of intra-ventricularly injected lipopolysaccharide(LPS) on dopaminergic(DA) neurons in the substantia nigra and to explore the role of brain-derived neurotrophic factor(BDNF) in the long-term degeneration of dopaminergic neurons in rats. Methods Altogether 48 healthy male SD rats were assigned into LPS-injected group and saline-injected group randomly. All injections were made intra-ventricularly on right side with LPS 20 μL(1.25 g/L)or saline 20 μL. The changes of dopaminergic neurons in the substantia nigra were studied by using tyrosine-hydroxylase(TH) immunohistochemical staining. The changes of BDNF were detected by immunohistochemical staining and enzyme immunoassay system(ELISA). Results The number of TH-positive neurons in the substantia nigra in LPS-injected rats decreased at 24 weeks after LPS injection. The number of TH-positive neurons in LPS-injected group was 75.4% of that in saline-injected group(P<0.01). The BDNF-positive cells in the substantia nigra in LPS-injected group increased markedly compared with saline-injected group at 4 weeks, while at 12 weeks and 24 weeks, the BDNF-positive cells in the substantia nigra in LPS-injected group decreased obviously compared with those in saline-injected group. The results of ELISA showed that BDNF protein levels in LPS-injected group were 186.3% of those of saline-injected group at 4 weeks(P<0.01). While at 12 weeks and 24 weeks post LPS injection, BDNF protein levels in the substantia nigra and corpus striatum of LPS-injected group were 42.3%(P<0.01) and 61.0%(P<0.05) of those in saline-injected group, respectively. Conclusion A single intra-ventricular administration of LPS in rats may result in a significant and a delayed loss of dopaminergic neurons in the substantia nigra. After LPS injection, a decrease of BDNF protein level in the substantia nigra occurs before the degeneration of dopaminergic neurons, suggesting that the decrease of BDNF may be one of the reasons that induced the loss of dopaminergic neurons induced by cerebral inflammation.

Key words: brain-derived neurotrophic factor, dopaminergic neurons, degeneration, lipopolysaccharide, rat