Dexmedetomidine-mediated neuroprotection against sevoflurane-induced brain development abnormality in fetal mice brain.

OBJECTIVE: Brain development is susceptible to external influences during the gestation period so the neurotoxicity of anesthetics has gained a lot of attention. We aimed to investigate the neurotoxicity of sevoflurane to fetal mice brain as well as the neuroprotective effects of dexmedetomidine. MATERIALS AND METHODS: Pregnant mice were treated with 2.5% sevoflurane for 6 hours. The changes in fetal brain development were assayed with immunofluorescence and western blot. The pregnant mice were intraperitoneally injected with dexmedetomidine or vehicle from gestation day (G) 12.5 to G15.5. RESULTS: Our results showed maternal sevoflurane exposure could not only inhibit neurogenesis but also lead to precocious generation of astrocytes in fetal mice brains. The fetal mice brain of sevoflurane group exhibited a significant inhibition in the activity of Wnt signaling and the expression of CyclinD1, Ngn2. Chronic dexmedetomidine administration could minimize the negative effects caused by sevoflurane by activating the Wnt signaling pathway. CONCLUSIONS: This study has uncovered a Wnt signaling-related mechanism of the neurotoxicity of sevoflurane and confirmed the neuroprotective effect of dexmedetomidine, which could provide pre-clinical evidence for clinical decision-making.

Lipoxin A4 attenuates radicular pain possibly by inhibiting spinal ERK, JNK and NF-κB/p65 and cytokine signals, but not p38, in a rat model of non-compressive lumbar disc herniation.

Inflammatory response induced by protrused nucleus pulposus (NP) has been shown to play a crucial role in the process of radicular pain. Lipoxins represent a unique class of lipid mediators that have anti-inflammatory and pro-resolving action. The present study was undertaken to investigate if intrathecal lipoxin A4 (LXA4) could alleviate mechanical allodynia in the rat models of application of NP to the L5 dorsal root ganglion (DRG). Non-compressive models of application of NP to L5 DRG were established and intrathecal catheterization for drug administration was performed in rats. Daily intrathecal injection of vehicle or LXA4 (10ng or 100ng) was performed for three successive days post-operation. Mechanical thresholds were tested and the ipsilateral lumbar (L4-L6) segment of spinal dorsal horns were removed for the determination of tumor necrosis factor-α (TNF-α), IL-1ß, transforming growth factor-ß1 (TGF-ß1) and IL-10 expression and NF-κB/p65, extracellular signal-regulated kinase (ERK), C-Jun N-terminal kinase (JNK) and P38 expression. Application of NP to DRG in rats induced mechanical allodynia, increased the expression of pro-inflammatory factors (TNF-α and IL-1ß), NF-κB/p65, the phosphorylated-ERK (p-ERK), -JNK (p-JNK) and -P38 (p-p38) and decreased the expression of anti-inflammatory cytokines (TGF-ß1 and IL-10) in the ipsilateral lumbar (L4-L6) segment of spinal dorsal horns. Intrathecal injection of LXA4 alleviated the development of neuropathic pain, inhibited the upregulation of pro-inflammatory cytokines (TNF-α and IL-1ß), upregulated the expression of anti-inflammatory cytokines (TGF-ß1 and IL-10) and attenuated the activation of NF-κB/p65, p-ERK, p-JNK, but not p-p38, in a dose-dependent manner. In this study, we have demonstrated that LXA4 potently alleviate radicular pain in a rat model of non-compressive lumbar disc herniation. The anti-inflammatory and pro-resolution properties of LXA4 have shown a great promise for the management of radicular pain caused by intervertebral disc herniation.