Departmental sources Background: Cerebral ischemia-reperfusion injury is a pivotal cause of deaths due to cerebrovascular accident. Increased research efforts are needed to reveal the mechanism underlying its aggravation or alleviation. In this study, the effects of dexmedetomidine post-conditioning on the HMGB1/TLR4/NF-kB signaling pathway in cerebral ischemia-reperfusion rats was explored. Material/Methods: Ninety rats were randomly divided into 5 groups-a sham group (Sham), a model group (I/R), a dexmedetomidine post-conditioning group (Dex), a recombinant high mobility group protein B1 group (rHMGB1), and a recombinant HMGB1+dexmedetomidine post-conditioning group (rHMGB1+Dex)-with 18 rats in each group. Longa grading, wet-dry weighing, TTC staining, HE staining, and immunohistochemical staining were used to assess brain damage. ELISA, RT-PCR, and Western blot analyses were performed to assess expression of IL-1b, TNF-a, IL-6, IL-8, HMGB1, TLR4, and NF-kB. Results: Compared with the I/R group, the neurological function score, brain water content, infarction area, and the number of COX-2-and IBA-1-positive cells in the Dex group were significantly lower, accompanied by downregulated expression of the HMGB1/TLR4/NF-kB pathway, alleviated inflammation, and oxidative stress injury in brain tissue. These trends were mostly reversed in the rHMGB1 group and rHMGB1+Dex group, but not in the Dex group. Furthermore, when compared to the Dex group, there were significant increases of H 2 O 2 , MDA, NO, IL-1b, TNF-a, IL-6, IL-8, HMGB1, TLR4, and p-P65 in the rHMGB1 group and rHMGB1+Dex group, in which a significant decrease of T-AOC, SOD, and p-IkBa was also detected. Conclusions: Dexmedetomidine post-conditioning can alleviate cerebral ischemia-reperfusion injury in rats by inhibiting the HMGB1/TLR4/NF-kB signaling pathway.

Departmental sources Background: Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that modulate critical metabolic activities, including apoptosis, proliferation, and differentiation modulation. Although numerous studies have focused on the damaging effects of BDNF on neurons, the underlying relationship between these effects remains unclear. In the present study, we investigated the protective effect of BDNF on neuronal injury induced by ropivacaine and assessed whether it is related to the Akt signaling pathway. Material/Methods: Human neuroblastoma cell line SH-SY5Y cells were stimulated with ropivacaine at different concentrations to induce neuronal injury. MTT analysis, flow cytometry, immunohistochemistry, qRT-PCR, and Western blot were used to investigate the proliferation activity, apoptotic level, and expression of Akt, PCNA, Bax, Bcl-2, and cleaved caspase-3, collectively demonstrating the underlying regulatory mechanisms. Results: Compared with the control group, the morphological damage and proliferation inhibition of SH-SY5Y cells induced by ropivacaine were dose-dependent and time-dependent, accompanied by a significant decrease in Akt expression. We treated cells with BDNF or SC79, which is a selective cell-permeable small molecule Akt activator. The results showed that, compared to the ropivacaine group, the morphological damage of neurons was alleviated; cell proliferation activity was enhanced; apoptotic rate was reduced; PCNA, Bcl-2, and phosphorylated Akt expression levels were increased; and Bax and caspase-3 gene and protein expression were decreased. We were able to reverse these effects by administering API-2, an Akt inhibitor. Conclusions: BDNF can alleviate ropivacaine-induced neuronal injury by activating Akt signaling pathway, consequently modulating the proliferation and apoptosis of neurons.