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Ocimum basilicum attenuates ethidium bromide-induced cognitive deficits and pre-frontal cortical neuroinflammation, astrogliosis and mitochondrial dysfunction in rats.

罗勒减轻溴化乙锭诱导的大鼠认知缺陷和额叶前皮质神经炎症、星形胶质细胞增生和线粒体功能障碍。

  • 影响因子:2.53
  • DOI:10.1007/s11011-020-00536-z
  • 作者列表:"Garabadu D","Singh D
  • 发表时间:2020-01-29
Abstract

:Multiple sclerosis (MS) is a chronic neurodegenerative disorder with clinical symptoms of neuroinflammation and demyelination in the central nervous system. Recently, herbal medicines are clinically effective against MS as the current disease-modifying drugs have limited effectiveness. Hence, the present study evaluated the therapeutic potential of Ocimum basilicum essential oil (OB) in ethidium bromide (EB)-induced cognitive deficits in the male rats. Further, the effect of OB (50, 100 and 200 μL/kg) was evaluated on EB-induced neuroinflammation, astrogliosis and mitochondrial dysfunction in the pre-frontal cortex (PFC) of the animals. The EB was injected through bilateral intracerebroventricular route into hippocampus to induce MS-like manifestations in the rats. OB (100 and 200 μL/kg) and Ursolic acid (UA) significantly reduced the EB-induced cognitive deficits in Morris water maze and Y-maze test paradigms. OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced neuroinflammation in terms of increase in the levels of pro-inflammatory cytokines (TNF-alpha and IL-6) in the rat PFC. Further, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced astrogliosis in terms of increase in the levels of GFAP (Glial fibrillary acidic protein) and Iba-1 (Ionized calcium binding adaptor molecule-1) in the rat PFC. In addition, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced decrease in the mitochondrial function, integrity, respiratory control rate and ADP/O in the PFC of the rodents. Moreover, OB (100 and 200 μL/kg) and UA significantly reduced the EB-induced mitochondria-dependent apoptosis in the PFC of the rat. Hence, it can be presumed that OB could be a potential alternative drug candidate in the pharmacotherapy of MS.

摘要

多发性硬化 (MS) 是一种慢性神经退行性疾病,临床症状为中枢神经系统的神经炎症和脱髓鞘。最近,草药对 MS 临床有效,因为目前的疾病修饰药物的有效性有限。因此,本研究评价了罗勒精油 (OB) 对溴化乙锭 (EB) 诱导的雄性大鼠认知缺陷的治疗潜力。此外,评估了 OB (50 、 100 和 200 μ l/kg) 对 EB 诱导的额前皮质 (PFC) 神经炎症、星形胶质细胞增生和线粒体功能障碍的影响动物。将 EB 经双侧侧脑室注入海马,诱导大鼠出现 MS 样表现。OB (100 和 200 μ l/kg) 和熊果酸 (UA) 显著降低了 EB 诱导的 Morris 水迷宫和 Y 迷宫测试范式的认知缺陷。OB (100 和 200 μ l/kg) 和 UA 显著减轻 EB 诱导的神经炎症,增加促炎细胞因子 (TNF-α 和 IL-6) 水平在大鼠 PFC。此外,OB (100 和 200 μ l/kg) 和 UA 通过 GFAP (胶质纤维酸性蛋白) 水平的增加显著减弱 EB 诱导的星形胶质细胞增生和 Iba-1 (离子钙结合接头分子-1) 在大鼠 PFC。此外,OB (100 和 200 μ l/kg) 和 UA 显著减弱 EB 诱导的线粒体功能、完整性、啮齿类动物 PFC 中的呼吸控制率和 ADP/O。此外,OB (100 和 200 μ l/kg) 和 UA 显著降低了 EB 诱导的大鼠 PFC 中线粒体依赖性凋亡。因此,可以推测 OB 可能是 MS 药物治疗中的潜在替代药物候选者。

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相关文献
影响因子:2.53
发表时间:2020-01-29
DOI:10.1007/s11011-020-00536-z
作者列表:["Garabadu D","Singh D"]

METHODS::Multiple sclerosis (MS) is a chronic neurodegenerative disorder with clinical symptoms of neuroinflammation and demyelination in the central nervous system. Recently, herbal medicines are clinically effective against MS as the current disease-modifying drugs have limited effectiveness. Hence, the present study evaluated the therapeutic potential of Ocimum basilicum essential oil (OB) in ethidium bromide (EB)-induced cognitive deficits in the male rats. Further, the effect of OB (50, 100 and 200 μL/kg) was evaluated on EB-induced neuroinflammation, astrogliosis and mitochondrial dysfunction in the pre-frontal cortex (PFC) of the animals. The EB was injected through bilateral intracerebroventricular route into hippocampus to induce MS-like manifestations in the rats. OB (100 and 200 μL/kg) and Ursolic acid (UA) significantly reduced the EB-induced cognitive deficits in Morris water maze and Y-maze test paradigms. OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced neuroinflammation in terms of increase in the levels of pro-inflammatory cytokines (TNF-alpha and IL-6) in the rat PFC. Further, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced astrogliosis in terms of increase in the levels of GFAP (Glial fibrillary acidic protein) and Iba-1 (Ionized calcium binding adaptor molecule-1) in the rat PFC. In addition, OB (100 and 200 μL/kg) and UA significantly attenuated the EB-induced decrease in the mitochondrial function, integrity, respiratory control rate and ADP/O in the PFC of the rodents. Moreover, OB (100 and 200 μL/kg) and UA significantly reduced the EB-induced mitochondria-dependent apoptosis in the PFC of the rat. Hence, it can be presumed that OB could be a potential alternative drug candidate in the pharmacotherapy of MS.

影响因子:4.30
发表时间:2020-01-24
来源期刊:Experimental neurology
DOI:10.1016/j.expneurol.2020.113212
作者列表:["Bertrand SJ","Zhang Z","Patel R","O'Ferrell C","Punjabi NM","Kudchadkar SR","Kannan S"]

METHODS::Sleep fragmentation is an increase in sleep-wake transitions without an overall decrease in total sleep time. Sleep fragmentation is well documented during acute and chronic hospitalization and can result in delirium and memory problems in children. Sleep fragmentation is also often noted in neurodevelopmental disorders. However, it is unclear how sleep fragmentation independent of disease affects brain development and function. We hypothesized that acute sleep fragmentation during the neonatal period in otherwise healthy animals would result in neuroinflammation and would be associated with abnormalities in cognitive development. The orbital shaker method was used to fragment sleep for 72 h in postnatal day 3 New Zealand white rabbit kits (fragmentation group). To control for maternal separation, the sham group was separated from the dam and maintained in the same conditions without undergoing sleep fragmentation. A naïve control group remained with the dam. Kits underwent behavioral testing with novel object recognition and spontaneous alternation T-maze tests at 2-3 weeks post-fragmentation and were sacrificed 3-50 days after fragmentation. Sleep fragmentation resulted in acute and chronic changes in microglial morphology in the hippocampus and cortex, and regional differences in mRNA expression of pro- and anti-inflammatory cytokines at 3, 7 and 50 days post-fragmentation. Impaired novel object recognition and a longer latency in T-maze task completion were noted in the fragmented kits. This was in spite of normalization of sleep architecture noted at 2 months of age in these kits. The results indicate that transient neonatal sleep fragmentation results in short-term and long-term immune alterations in the brain, along with diminished performance in cognitive tasks long-term.

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影响因子:1.52
发表时间:2020-01-27
来源期刊:World neurosurgery
DOI:10.1016/j.wneu.2020.01.108
作者列表:["Middlebrooks EH","Lin C","Okromelidze L","Lu CQ","Tatum WO","Wharen RE Jr","Grewal SS"]

METHODS:BACKGROUND:Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a recently approved therapy for patients with drug-resistant epilepsy. To date, there is a poor understanding of the mechanism of action and lack of in vivo biomarkers. We propose a method for investigating the in vivo stimulation effects using blood-oxygen-level dependent (BOLD) MRI and present the brain activation pattern associated with ANT DBS. METHODS:Two patients undergoing ANT DBS for epilepsy underwent BOLD MRI using a block design after the DBS was programmed to alternate ON/OFF in 30 second blocks. The scanner was triggered utilizing surface electrophysiological recording to detect the DBS cycle. Nine total runs were obtained and were analyzed using a general linear model. RESULTS:Active ANT stimulation produced activation within several areas of the brain, including the thalamus, bilateral anterior cingulate and posterior cingulate cortex, precuneus, medial prefrontal cortex, amygdala, ventral tegmental area, hippocampus, striatum, and right angular gyrus. CONCLUSIONS:Utilizing block-design BOLD MRI, we were able to show widespread activation resulting from ANT DBS. Overlap with multiple areas of both the default mode and limbic networks was shown suggesting that these nodes may modulate the effect of seizure control with ANT DBS.

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