Minocycline relieves neuropathic pain in rats with spinal cord injury via activation of autophagy and suppression of PI3K/Akt/mTOR pathway.

OBJECTIVE: In this study, we studied whether minocycline hydrochloride improved neuropathic pain induced by spinal cord injury (SCI) in rats through PI3K/Akt pathway. METHODS: The SCI was induced by compressed at level of T9-T11 of spinal cord in Sprague Dawley male rats. Animals were given different concentrations of minocycline (3 mg/kg, 30 mg/kg, 90 mg/kg) at the first and 24 h after SCI, then subsequently every 7, 12, 16, 20, 25 days via peroral route. The locomotor function was assessed by Basso Mouse Scale (BMS). The changes of spinal cord tissues were observed by HE. The inflammatory cytokines in spinal cord, IL-6, IL-1ß and TNF-α, were measured by ELISA. The LC3B levels of spinal cord were observed by immunofluorescence. The autophagy related proteins and PI3K/AKT pathway related proteins were analysed by Western blot. Furthermore, the PI3K/AKT pathway inhibitor LY294002, and activator IGF-1 were used to confirm the mechanism of minocycline. RESULTS: Contrasted to sham group, the inflammatory response in spinal cord was enhanced after SCI. Compared with the SCI rats, minocycline treatment significantly improved the locomotor activity, pathological injury of spinal cord, suppressed the levels of inflammatory factors. In addition, minocycline treatment upregulated autophagy response in damaged spinal cord through increasing LC3B, Beclin-1 and decreasing P62. The results of mechanism study showed that minocycline treatment clearly suppressed phosphorylation of PI3K, Akt and mTOR proteins expression. CONCLUSION: Minocycline could improve neuropathic pain induced by SCI through activating autophagy and inhibiting PI3K/AKT/mTOR pathway.

HYDROMORPHONE MITIGATES CARDIOPULMONARY BYPASS-INDUCED ACUTE LUNG INJURY BY REPRESSING PYROPTOSIS OF ALVEOLAR MACROPHAGES.

ABSTRACT: Introduction: Acute lung injury (ALI) is a devastating pulmonary illness with diffuse inflammatory responses. Hydromorphone (Hyd) is an opioid agonist used for relieving moderate-to-severe pain. The present work investigated the effect of Hyd on cardiopulmonary bypass (CPB)-induced ALI by regulating pyroptosis of alveolar macrophages (AMs). Methods: Rats were subjected to CPB, followed by Hyd treatment. The lung injury in rat lung tissues was appraised by the ratio of lung wet/dry weight (weight), histological staining, and the total protein concentrations in bronchoalveolar lavage fluid, and lung function was assessed by oxygenation index and respiratory index, and lung macrophage pyroptosis was observed by fluorescence staining. Alveolar macrophages were separated and pyroptosis was determined by western blot assay and enzyme-linked immunosorbent assay. The expression patterns of nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1), nod-like receptor protein 3 (NLRP3), N-terminal gasdermin-D, and cleaved caspase-1 were examined by real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry assays. The impact of NLRP3 or Nrf2 on pyroptosis of AMs and CPB-induced ALI was observed after treatment of nigericin (NLRP3 agonist) or ML385 (Nrf2 inhibitor). Results: Hyd attenuated CPB-induced lung injury as manifested by reductions in lung inflammation and edema, the scores of lung injury, the ratio of lung wet/dry weight, and the total protein concentrations in bronchoalveolar lavage fluid. Besides, Hyd repressed NLRP3 inflammasome-mediated pyroptosis of AMs after CPB treatment. Hyd upregulated Nrf2/HO-1 expression levels to repress NLRP3 inflammasome-mediated pyroptosis. Treatment of nigericin or ML385 counteracted the role of Hyd in ameliorating pyroptosis of AMs and CPB-induced ALI. Conclusions: Hyd alleviated NLRP3 inflammasome-mediated pyroptosis and CPB-induced ALI via upregulating the Nrf2/HO-1 pathway, which may be achieved by AMs.

Magnetic Resonance Imaging Features under Deep Learning Algorithms in Evaluated Cerebral Protection of Craniotomy Evacuation of Hematoma under Propofol Anesthesia.

This study aimed to explore the value of magnetic resonance imaging (MRI) features based on deep learning super-resolution algorithms in evaluating the value of propofol anesthesia for brain protection of patients undergoing craniotomy evacuation of the hematoma. An optimized super-resolution algorithm was obtained through the multiscale network reconstruction model based on the traditional algorithm. A total of 100 patients undergoing craniotomy evacuation of hematoma were recruited and rolled into sevoflurane control group and propofol experimental group. Both were evaluated using diffusion tensor imaging (DTI) images based on deep learning super-resolution algorithms. The results showed that the fractional anisotropic image (FA) value of the hind limb corticospinal tract of the affected side of the internal capsule of the experimental group after the operation was 0.67 ± 0.28. The National Institute of Health Stroke Scale (NIHSS) score was 6.14 ± 3.29. The oxygen saturation in jugular venous (SjvO2) at T4 and T5 was 61.93 ± 6.58% and 59.38 ± 6.2%, respectively, and cerebral oxygen uptake rate (CO2ER) was 31.12 ± 6.07% and 35.83 ± 7.91%, respectively. The difference in jugular venous oxygen (Da-jvO2) at T3, T4, and T5 was 63.28 ± 10.15 mL/dL, 64.89 ± 13.11 mL/dL, and 66.03 ± 11.78 mL/dL, respectively. The neuron-specific enolase (NSE) and central-nerve-specific protein (S100ß) levels at T5 were 53.85 ± 12.31 ng/mL and 7.49 ± 3.16 ng/mL, respectively. In terms of the number of postoperative complications, the patients in the experimental group were better than the control group under sevoflurane anesthesia, and the differences were substantial (P < 0.05). In conclusion, MRI images based on deep learning super-resolution algorithm have great clinical value in evaluating the degree of brain injury in patients anesthetized with propofol and the protective effect of propofol on brain nerves.