Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsis-associated encephalopathy.

Inflammation plays a crucial role in the initiation and progression of sepsis, and it also induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy (SAE). Parvalbumin (PV) interneurons are pivotal contributors to cognitive processes in various central dysfunctions including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid (GABA)ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to the SAE mice induced by lipopolysaccharide (LPS). Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence analysis demonstrated decreased PV expression in the cornu ammonis 1 (CA1) region of the hippocampus following LPS treatment, which was alleviated by oxytocin. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to improved cognitive function. In conclusion, cognitive function improved after oxytocin treatment. The number of PV neurons in the hippocampal CA1 region and the balance of excitatory/inhibitory synaptic transmission on PV interneurons, as well as changes in local field potential gamma oscillations in the hippocampal CA1 region, may represent its specific mechanisms.

Vitamin D intake as well as circulating 25-hydroxyvitamin D level and risk for the incidence and recurrence of colorectal cancer precursors: A meta-analysis.

Objective: Vitamin D consumption and circulating 25(OH)D level are associated with decreased risk of colorectal cancer (CRC) and colorectal adenoma (CRA), but few studies have assessed their relationship with the incidence and recurrence of CRC precursors. Therefore, we performed this meta-analysis to further evaluate the association. Methods: We searched PubMed, Web of Science, Scopus and Embase databases in English until August 2021. Studies evaluating the association of vitamin D intake and circulating 25(OH)D level with risk of CRC precursors were included. A random-effects model was used to pool the risk estimates. Results: A total of 48 studies were selected for inclusion. The CRC precursors incidence was negatively correlated with total vitamin D intake (RR = 0.84 95%CI: 0.80-0.88) and circulating 25(OH)D level (RR = 0.79 95%CI: 0.67-0.92). However, vitamin D intake and circulating 25(OH)D level did not show significant effects on the risk of CRC precursors recurrence. For dose-response analysis, evidence of a linear association was found between CRC precursors incidence and circulating 25(OH)D level, and the risk decreased by 14% per 10 ng/ml increment of circulating 25(OH)D level (RR = 0.86 95% CI: 0.75-0.99). Conclusion: Vitamin D intake and circulating 25(OH)D level can play an effective role in reducing the risk of incidence of CRC precursors. However, they have not prevented the recurrence of CRC precursors.

[Effect of mild hypothermia on the expression of acid-sensing ion channels 1a and 2a following global cerebral ischemia-reperfusion in rats].

OBJECTIVE: To investigate the effects of mild hypothermia on the expression of ASIC1a and ASIC2a in the rat hippocampus following global cerebral ischemia-reperfusion, so as to speculate the underlying mechanisms of neuroresuscitation. METHODS: Ninety five male SD rats were randomly divided into five groups (n = 19): sham operation group (I), model group (II), mild hypothermia group (III), PcTX1 group (IV), mild hypothermia combined PcTX1 group (V). Transient (15 min) global cerebral ischemia was induced by the four-vessel occlusion. PcTX1 (500 ng/ml) 6 µl were injected into lateral cerebral ventricle immediately after reperfusion in group IV and V, while the equal volume of normal saline was injected into lateral cerebral ventricle immediately after reperfusion in the other three groups. At the same time, mild hypothermia after reperfusion was performed and lasted for 6 hours in group III and V, the rectal temperature was reduced to 32 - 33°C within 15 min, while it was maintained at 36 - 37°C by lamp in other three groups. Determination the expression of ASIC1a and ASIC2a protein at 6 h and 24 h of reperfusion, and the expression of ASIC1a and ASIC2a mRNA at 24 h of reperfusion. Observe the pathomorphological changes of hippocampal CA1 neurons at 24 h of reperfusion. Detect the brain water content at 72 h of reperfusion. RESULTS: The difference in the expression of ASIC1a mRNA and protein among the groups was not changed significantly (P > 0.05). Compared with group I, the expression of ASIC2a mRNA and ASIC2a protein was up-regulated in other groups (P < 0.05). It was significantly higher in group III and V than in group II and IV (P < 0.05). Compared to 6 h of reperfusion, the expression of ASIC2a protein was higher in group II, III, IV and V respectively after 24 h of reperfusion. Compared to group I, the number of pyramidal cells in CA1 region of hippocampus in group II, III, IV and V were decreased at 24 h of reperfusion (P < 0.01). Compared to group II, the number of pyramidal cells in CA1 region of hippocampus in group III, IV and V were increased at 24 h of reperfusion (P < 0.01); and compared to group III and IV, the number of pyramidal cells at 24 h of reperfusion in group V was significantly higher (P < 0.01). Compared to group I, the content of brain water in II, III and IV group were increased at 72 h of reperfusion (P < 0.01). Compared to group II, the content of brain water in group III, IV and V were decreased at 72 h of reperfusion (P < 0.01). Giving mild hypothermia or PcTX1 could alleviate the damage in CA1 region of hippocampus, with the best effect in group V, which administers PcTX1 combined mild hypothermia. CONCLUSION: Mild hypothermia attenuates global cerebral ischemia-reperfusion of rat, which may up-regulate the expression of ASIC2a mRNA and protein. Mild hypothermia combined by PcTX1 could induce neuroresuscitation.

Effects of hydrogen-rich saline treatment on polymicrobial sepsis.

BACKGROUND: Hydrogen has been reported to selectively reduce hydroxyl radicals and peroxynitrite anion in many pathologic processes. This study aimed to test the hypothesis that hydrogen-rich saline (HRS) may ameliorate organ dysfunction in a rat model of polymicrobial sepsis. METHODS: Sepsis was induced in male Sprague-Dawley rats by cecal ligation and puncture (CLP). Twenty-four rats were equally assigned to Sham group, CLP group, and CLP + HRS group (n = 8). At 0, 6, and 18 h after CLP or sham operation, rats received an intraperitoneal injection of HRS (5 mL/kg) or the same volume of normal saline. Malondialdehyde, superoxide dismutase activities, inflammatory mediators, pulmonary nitric oxide, myeloperoxidase activities, wet-to-dry weight ratio, histologic scores, apoptotic analysis, alanine aminotransferase, creatinine, and blood urea nitrogen were assessed at 24 h after operation. The 7-d survival rate was also recorded. RESULTS: HRS administration significantly reduced the serum high-mobility group box, alanine aminotransferase, creatinine, and blood urea nitrogen levels; the pulmonary interleukin 6, high-mobility group box, nitric oxide, and malondialdehyde levels; and the wet-to-dry weight ratio, total histologic scores, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells, whereas it increased the superoxide dismutase activities 24 h after CLP when compared with the CLP group. However, there was no significant difference in survival rate between the CLP + HRS and CLP groups. CONCLUSIONS: HRS has potential protective effects against sepsis by decreasing proinflammatory responses, oxidative stress, and apoptosis in a rat model of polymicrobial sepsis.