Conditioned Medium Derived from Salidroside-Pretreated Mesenchymal Stem Cell Culture Ameliorates Mouse Lipopolysaccharide-Induced Cerebral Neuroinflammation-Histological and Immunohistochemical Study

ABSTRACT

BACKGROUND AND OBJECTIVES: Neuroinflammation is involved in the pathogenesis of neurodegenerative disorders. Conditioned medium (CM) derived from bone marrow mesenchymal stem cells (MSCs) revealed substantial benefits due to its rich content of trophic factors. Salidroside (Sal), extracted from Rhodiola rosea, is known for its anti-inflammatory and neuroprotective effects. This study was designed to investigate the effect of Sal pretreated CM (CM-Sal) derived from bone marrow MSCs in lipopolysaccharide (LPS) induced neuroinflammation. MATERIAL AND METHODS: Fifty adult male mice were equally divided into 5 groups Group I (Normal Control), Group II (LPS) single 0.8 mg/kg LPS intraperitoneally; Group III (LPS-DMEM), Group IV (LPS-CM) and Group V (LPS-CM-Sal) LPS was injected as group II followed, 24 hours later, by intranasal injection of 50 μl of filtered serum-free Dulbecco's Modified Eagle's medium (DMEM), CM or CM-Sal, respectively, twice daily for 4 days. Animals were sacrificed at day 6 and paraffin cerebral sections were subjected to Hematoxylin and Eosin staining and immunohistochemistry with caspase 3 (apoptosis), glial fibrillary acidic protein GFAP (astrocytes) and CD68 (active microglia) followed by quantitative morphometric study. RESULTS: Examination of LPS and LPS-DMEM groups revealed neuronal apoptosis with reactive astrogliosis and increased active microglia. LPS-CM and LPS-CM-Sal groups showed less apoptosis, less astrocytes and less active microglia. The regression in neuroinflammation was more evident in LPS-CM-Sal group and the difference was statistically significant compared to other groups. CONCLUSION: CM-Sal derived from MSCs culture elicited significant histopathological improvement in LPS induced neuroinflammation which could be used as new therapeutic modality.