Salidroside provides neuroprotection by modulating microglial polarization after cerebral ischemia

Abstract

BackgroundFollowing stroke, microglia can be driven to the “classically activated” pro-inflammatory (M1) phenotype and the “alternatively activated” anti-inflammatory (M2) phenotype. Salidroside (SLDS) is known to inhibit inflammation and to possess protective effects in neurological diseases, but to date, the exact mechanisms involved in these processes after stroke have yet to be elucidated. The purpose of this study was to determine the effects of SLDS on neuroprotection and microglial polarization after stroke.MethodsMale adult C57/BL6 mice were subjected to focal transient cerebral ischemia followed by intravenous SLDS injection. The optimal dose was determined by evaluation of cerebral infarct volume and neurological functions. RT-PCR and immunostaining were performed to assess microglial polarization. A transwell system and a direct-contact coculture system were used to elucidate the effects of SLDS-induced microglial polarization on oligodendrocyte differentiation and neuronal survival.ResultsSLDS significantly reduced cerebral infarction and improved neurological function after cerebral ischemia. SLDS treatment reduced the expression of M1 microglia/macrophage markers and increased the expression of M2 microglia/macrophage markers after stroke and induced primary microglia from M1 phenotype to M2 phenotype. Furthermore, SLDS treatment enhanced microglial phagocytosis and suppressed microglial-derived inflammatory cytokine release. Cocultures of oligodendrocytes and SLDS-treated M1 microglia resulted in increased oligodendrocyte differentiation. Moreover, SLDS protected neurons against oxygen glucose deprivation by promoting microglial M2 polarization.ConclusionsThese data demonstrate that SLDS protects against cerebral ischemia by modulating microglial polarization. An understanding of the mechanisms involved in SLDS-mediated microglial polarization may lead to new therapeutic opportunities after stroke.

Salidroside protected against MPP+‐induced Parkinson's disease in PC12 cells by inhibiting inflammation, oxidative stress and cell apoptosis

“…As a constituent of the commonly used traditional Chinese medicine R. rosea, SAL has proven to have a variety of positive pharmacological effects, including protective effects against stroke and other neurodegenerative diseases [20,21]. In the present study, a common in vitro PD model (MPP + -treated PC12 cells) was used to determine the protective effect of SAL.…”

Modulators of microglia activation and polarization in ischemic stroke (Review)

“…in Mcao model mice, rosiglitazone decreased the numbers of iba1 + /cd16 + M1 microglia and increased the numbers of iba1 + /cd206 + M2 microglia following stroke, which improved the overall long-term white matter integrity (61,112). in addition to western medicines, some traditional chinese medicines can also be used to regulate microglia polarization (16,25,113); a study by Yang et al (16) demonstrated that baicalein significantly decreased the expression levels of the M1 markers, cd16 and cd86, and increased the expression levels of the M2 markers, CD163 and CD206. Additionally, expression levels of the proinflammatory factors, il-6, il-18 and TnF-α were decreased upon inhibition of nF-κB signaling following baicalein treatment in Mcao model mice (16).…”

BRD4 inhibition attenuates inflammatory response in microglia and facilitates recovery after spinal cord injury in rats

“…25 To explore the effects of BRD4 inhibition on polarization in microglia, we repressed BRD4 by using JQ1 in HAPI cells. 25 To explore the effects of BRD4 inhibition on polarization in microglia, we repressed BRD4 by using JQ1 in HAPI cells.…”

“…M1 polarization represents pro-inflammatory phenotypes in microglia leading to higher production of pro-inflammatory cytokines. 25 To explore the effects of BRD4 inhibition on polarization in microglia, we repressed BRD4 by using JQ1 in HAPI cells. Figure 4A, the results of the morphological study showed that HAPI cells transformed into amoeboid shapes after LPS stimulation, representing M1 polarization, which was prevented partly by treatment of JQ1.…”