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Neurocognition is a severe, neurological challenge caused due to sevoflurane application for induction of anaesthesia. The plan of this study is to investigate the effect of fingolimod loaded niosomes on the cognitive impairment induced by sevoflurane. Span 40 and cholesterol were used in reverse phase evaporation techniques for the preparation of fingolimod -loaded niosomes. The positively charged niosomes were obtained by using chloride salts of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). The Fingolimod loaded niosomes has average particle size of 223.5 nm and the surface charge measured as + 8.7 ± 1.2 mV in presence of DOTAP. The Fingolimod loaded niosomes formulation shows higher entrapment efficiency. Fingolimod loaded positively charged niosomes were efficiently retained drug and increase the sustain release property. Fingolimod niosomes increases the spontaneous alternation in Y maze and reduces the escape latency in the Morris water maze test, which leads to significant (p < 0.01) improvement in spatial short-term and long-term memory. The neuronal death in the hippocampus due to the sevoflurane exposure was attenuated by fingolimod loaded niosomes, which was proved by histopathological study. It could be defined that fingolimod loaded niosomes attenuates the sevoflurane induced cognitive impairment.
Asunto(s)
Disfunción Cognitiva , Liposomas , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Clorhidrato de Fingolimod/farmacología , Humanos , Tamaño de la Partícula , SevofluranoRESUMEN
Background: Executive dysfunction in children with attention deficit hyperactivity disorder (ADHD) is thought to be closely related to the prefrontal cortex (PFC). However, there is controversy over the activation of the PFC in children with ADHD. Differences could be related to the subtype. Meanwhile, no study to date has used functional near-infrared spectroscopy (fNIRS) to explore the differences between subtypes. Thus, this study aimed to explore the activation of the PFC in children with different subtypes of ADHD during executive function task. Methods: Participants in this study include typically developing (TD) children (n = 28), ADHD-predominantly inattentive (ADHD-PI) (n = 39) and ADHD-combined (ADHD-C) (n = 24). To examine the executive function of ADHD, the Go/No-go task is chosen to assess the response inhibition function. The activation of PFC in all participants during the Go/No-go task was recorded by fNIRS. Meanwhile, behavioral data were also recorded. Results: Both TD and ADHD children activated the right PFC [middle frontal gyrus (MFG) and inferior frontal gyrus (IFG)] during response inhibition. However, the range and degree of activation differed among these groups. Compared with TD children, those with ADHD-PI had a smaller extent of activation in the right PFC, and those with ADHD-C only had a tendency to enhance activation. In addition, children with ADHD-PI and ADHD-C had impaired activation of the temporal gyrus. Besides, compared with ADHD-C and TD, those with ADHD-PI also had impaired activation of the right precentral gyrus (PG), and the supplementary motor area (SMA). Compared with ADHD-PI, ADHD-C showed decreased activation of the right MFG. The activation of Ch34 (BA44, rPFC) in children with ADHD-PI and ADHD-C was negatively correlated with their clinical symptoms. Conclusion: The activation of the PFC in children with different subtypes of ADHD has both commonalities and differences. The degree of activation of the right PFC Ch34 in children with ADHD is negatively correlated with clinical symptoms. fNIRS could be served as a candidate hemodynamic biomarker for the diagnosis of ADHD.
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BACKGROUND: Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8) ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve. RESULTS: Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG) ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. CONCLUSIONS: TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.
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Dolor Crónico/metabolismo , Ganglios Espinales/metabolismo , Canales Catiónicos TRPM/fisiología , Animales , Modelos Animales de Enfermedad , Hiperalgesia/metabolismo , Masculino , Nociceptores/metabolismo , Ratas , Ratas Sprague-Dawley , Neuropatía Ciática/metabolismo , Canales Catiónicos TRPM/antagonistas & inhibidores , Factores de TiempoRESUMEN
OBJECTIVE: The aim of this study was to analyze the effect of tirofiban on new cerebral microhemorrhage after mechanical thrombectomy in patients with acute ischemic stroke. METHODS: In total, 203 patients with acute ischemic stroke treated by mechanical thrombectomy in our department of neurology were enrolled as the research objects. The patients were divided into two groups: the patients who used tirofiban within 24 h after surgery were assigned to the study group (78 subjects), while patients who did not use tirofiban were assigned to the conventional group (125 subjects). Magnetic resonance imaging was used to detect new-onset cerebral microbleeds in patients with stroke after surgery. The National Institute of Health Stroke Scale, modified ranking scale, and activity of daily living scale were used to assess the prognosis of patients, and the general data and the occurrence of adverse effects between two groups were compared to comprehensively evaluate the efficacy and safety of tirofiban. RESULTS: The proportion of atrial fibrillation in the research group was significantly lower than that in the conventional group. The research group had a much lower rate of new-onset cerebral microbleeds than the conventional group (p<0.001). There was no significant difference in the proportion of adverse reactions between the two groups (p>0.05). CONCLUSION: The application of tirofiban in mechanical thrombectomy of patients with acute ischemic stroke has high safety, effectively reduces the occurrence of new cerebral microhemorrhage, and provides a guarantee for patient safety.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/tratamiento farmacológico , Hemorragia Cerebral/tratamiento farmacológico , Fibrinolíticos/efectos adversos , Humanos , Accidente Cerebrovascular/tratamiento farmacológico , Trombectomía , Tirofibán , Resultado del TratamientoRESUMEN
PURPOSE: The current study was conducted in order to investigate the role of Forkhead box O1 and p21-mediated macrophage polarization in postoperative cognitive dysfunction induced by sevoflurane. METHODS: There involved a total of 30 healthy mice that were randomly divided into two groups: control group (without any treatment) and anaesthesia group (treated with sevoflurane inhalation). The effects of sevoflurane on cognitive function (memory) in mice were studied by trace fear conditioned reflex, and the effects of systemic inflammation and behavior after operation were measured by enzyme-linked immunosorbent assay (ELISA), the concentrations of CD163 and tumor necrosis factor-α (TNF-α) were measured. The expression of macrophage phenotype was observed by immunofluorescence staining, the expression levels of M1 and M2 markers mRNA were detected by real-time fluorescence quantitative PCR (RT-PCR), and the expression levels of FoxO1 and p21 were analyzed by immunoblotting (Western blot). RESULTS: Compared with the control group, the freezing time in the anesthesia group was lower than that in the control group (P<0.01), indicating that sevoflurane anesthesia led to the decrease of cognitive ability. The blood concentrations of CD163 and TNF-α increased significantly at 24 h after the operation with sevoflurane anesthesia (P<0.05). Fluorescence microscopic observation showed that M2 was the main type of macrophages in normal tissues, while M1 and M2 phenotypes were highly expressed in sevoflurane anesthetized tissues at the same time, especially in M1 phenotypes (P<0.01). The polarization of macrophages in the anesthetic group showed the high level of M1 mRNA, and the expression levels of TNF-α, monocyte chemotactic protein 1(MCP-1) and Interleukin-6 (IL-6)mRNA in the anesthetic group were significantly higher than those in the control group (P<0.05). The expression levels of M2 mRNA such as transforming growth factor-ß (TGF-ß) and IL-10 were significantly lower than those in the control group (P<0.05). Compared with the control group, the expression of FoxO1 and p21 protein in the anesthesia group was significantly lower than that in the control group with a significant statistical difference (P<0.01). CONCLUSION: This study offers a theoretical basis and insight for further understanding of the prevention and treatment of cognitive dysfunction induced by anesthetic drugs.
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Anestésicos por Inhalación/efectos adversos , Polaridad Celular/fisiología , Proteína Forkhead Box O1/metabolismo , Macrófagos/metabolismo , Complicaciones Cognitivas Postoperatorias/metabolismo , Sevoflurano/efectos adversos , Animales , Citocinas/metabolismo , Hipocampo/metabolismo , Activación de Macrófagos , Masculino , Ratones , Complicaciones Cognitivas Postoperatorias/inducido químicamenteRESUMEN
BACKGROUND: An increasing number of hospitals have carried out neonatal thoracoscopic assisted repair of congenital diaphragmatic hernia (CDH). METHODS: The 26 cases received thoracoscopic-assisted repair (observation group) and 44 cases open repair (control group). General anesthesia was performed with endotracheal intubation using a trachea cannula without cuff. The general preoperative data, intraoperative hemodynamic parameters, intraoperative surgical conditions, postoperative complications, postoperative recovery condition, postoperative survival rate and recurrence rate were recorded. RESULTS: The intraoperative mean arterial pressure and heart rate at each time point in observation group were more stable and effective than those in control group (all P < 0.001). The number of manual ventilation, SpO2 < 90% and hypercapnia cases were significantly lower than those in control group (all P < 0.05). Intraoperative bleeding, incision length and operation duration were significantly lower in observation group compared with control group (all P < 0.001). No significant differences were seen between the two groups in postoperative complications including pulmonary infection, incision infection, pulmonary hypertension, hemorrhage, and scleredema (all P > 0.05). The duration of postoperative mechanical ventilation, antibiotic use and hospitalization in observation group was significantly shorter than those in control group (all P < 0.05). There was no significant difference in postoperative survival rate and recurrence rate between the two groups (both P > 0.05). CONCLUSION: The intraoperative hemodynamic parameters of CDH repair under thoracoscopy were more stable, the duration of postoperative mechanical ventilation, antibiotic use and hospitalization were shortened, and the therapeutic effect was better.