Somatostatin (SST) is a neuromodulator which is abundant throughout the central 
nervous system (CNS) and has a crucial role in neurodegenerative disorders. 
However, little is known about the effects and mechanisms of SST in dopaminergic 
(DA) neurons in the context of Parkinson's disease (PD). In the present study, a 
model of PD was generated by injecting lipopolysaccharide (LPS) into the 
substantia nigra (SN) of rats in order to investigate the effects of SST on 
LPS-induced degeneration of DA in vivo. Intramural injection of LPS resulted in 
a significant loss of DA neurons, while reduction of neuronal death by SST 
pretreatment was confirmed using immunohistochemical staining for tyrosine 
hydroxylase and Nissl. In parallel, immunohistochemical detection of OX-42 and 
hydroethidine staining were employed to determine the activation of microglia 
and production of reactive oxygen species (ROS), respectively. It was found that 
SST inhibited the LPS-induced microglial activity and ROS production. ELISA 
revealed a decreased production of pro-inflammatory mediators, including tumor 
necrosis factor-α, interleukin-1β and prostaglandin E2 when SST was administered 
prior to LPS treatment. Western blot analysis showed that LPS-induced expression 
of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor κB 
(NF-κB) p-p65 was attenuated by administration of SST prior to LPS application. 
The results indicated that LPS-induced loss of nigral DA neurons was inhibited 
by SST and the observed effects of SST on neuroprotection were associated with 
suppression of microglial activation and the NF-κB pathway, ensuing decreases of 
neuroinflammation and oxidative stress. The present study therefore suggested 
that SST is beneficial for treating neurodegenerative diseases, such as PD, 
through inhibiting the activation of microglia.