Propofol affords no protection against delayed cerebral ischemia in a mouse model of subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is an important contributor to poor outcomes in aneurysmal subarachnoid hemorrhage (SAH) patients. We previously showed that volatile anesthetics such as isoflurane, sevoflurane and desflurane provided robust protection against SAH-induced DCI, but the impact of a more commonly used intravenous anesthetic agent, propofol, is not known. The goal of our current study is to examine the neurovascular protective effects of propofol on SAH-induced DCI. Twelve-week-old male wild-type mice were utilized for the study. Mice underwent endovascular perforation SAH or sham surgery followed one hour later by propofol infusion through the internal jugular vein (2 mg/kg/min continuous intravenous infusion). Large artery vasospasm was assessed three days after SAH. Neurological outcome assessment was performed at baseline and then daily until animal sacrifice. Statistical analysis was performed via one-way ANOVA and two-way repeated measures ANOVA followed by the Newman-Keuls multiple comparison test with significance set a

STAT3 inhibitor mitigates cerebral amyloid angiopathy and parenchymal amyloid plaques while improving cognitive functions and brain networks

Previous reports indicate a potential role for signal transducer and activator of transcription 3 (STAT3) in amyloid-β (Aβ) processing and neuritic plaque pathogenesis. In the present study, the impact of STAT3 inhibition on cognition, cerebrovascular function, amyloid pathology, oxidative stress, and neuroinflammation was studied using in vitro and in vivo models of Alzheimer\u27s disease (AD)-related pathology. For in vitro experiments, human brain vascular smooth muscle cells (HBVSMC) and human brain microvascular endothelial cells (HBMEC) were used, and these cultured cells were exposed to Aβ peptides followed by measurement of activated forms of STAT3 expression and reactive oxygen species (ROS) generation. Further, 6 months old 5XFAD/APOE4 (5XE4) mice and age-matched negative littermates were used for in vivo experiments. These mice were treated with STAT3 specific inhibitor, LLL-12 for 2 months followed by neurobehavioral and histopathological assessment. In vitro experiments showed exposure of cerebrovascular cells to Aβ peptides upregulated activated forms of STAT3 and produced STAT3-mediated vascular oxidative stress. 5XE4 mice treated with the STAT3-specific inhibitor (LLL-12) improved cognitive functions and functional connectivity and augmented cerebral blood flow. These functional improvements were associated with a reduction in neuritic plaques, cerebral amyloid angiopathy (CAA), oxidative stress, and neuroinflammation. Reduction in amyloid precursor protein (APP) processing and attenuation of oxidative modification of lipoprotein receptor related protein-1 (LRP-1) were identified as potential underlying mechanisms. These results demonstrate the broad impact of STAT3 on cognitive functions, parenchymal and vascular amyloid pathology and highlight the therapeutic potential of STAT3 specific inhibition for treatment of AD and CAA

Repeated multi-domain cognitive training prevents cognitive decline, anxiety and amyloid pathology found in a mouse model of Alzheimer disease

Education, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may delay the progression of various neurodegenerative diseases including Alzheimer\u27s disease. To investigate this protective effect, 3-month-old AP

Antiobesity effect of Safoof Mohazzil, a polyherbal formulation, in cafeteria diet induced obesity in rats

776-784  Obesity is reaching epidemic proportions all over the world yet it lacks adequate treatment. Most of the drugs have failed either due to ineffectiveness or adverse effects. Complementary and alternative system of medicine is being used since ancient times. However, many of them have not been tested for efficacy and safety using modern scientific methods. Therefore, the antiobesity effect of Safoof Mohazzil, a polyherbal formulation, was evaluated in cafeteria diet induced obesity in female Sprague Dawley rats. Animals weighing 100–150 g were divided into four groups (n=8) i.e. standard pellet diet, cafeteria diet control, cafeteria diet + Safoof Mohazzil and standard pellet diet plus Safoof Mohazzil. The formulation was administered orally at a dose of 1 g/kg/day for 14 weeks. At the end of study, cafeteria diet significantly increased body weight, Lee’s index, lipid profile (cholesterol and triglycerides), insulin and leptin levels as compared to standard pellet diet control group. Fourteen week treatment with Safoof Mohazzil significantly prevented the increase in body weight, Lee’s index, lipid profile, insulin and leptin levels as compared to cafeteria diet control group without affecting food and water intake. Safoof Mohazzil had no adverse effect on hepatic transaminases, locomotor activity and motor coordination. The study provides evidence for antiobesity effect of Safoof Mohazzil

Experimental Induction of Type 2 Diabetes in Aging-Accelerated Mice Triggered Alzheimer-Like Pathology and Memory Deficits

Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease constituting ~95% of late-onset non-familial/sporadic AD, and only ~5% accounting for early-onset familial AD. Availability of a pertinent model representing sporadic AD is essential for testing candidate therapies. Emerging evidence indicates a causal link between diabetes and AD. People with diabetes are >1.5-fold more likely to develop AD. Senescence-accelerated mouse model (SAMP8) of accelerated aging displays many features occurring early in AD. Given the role played by diabetes in the pre-disposition of AD, and the utility of SAMP8 non-transgenic mouse model of accelerated aging, we examined if high fat diet-induced experimental type 2 diabetes in SAMP8 mice will trigger pathological aging of the brain. Results showed that compared to non-diabetic SAMP8 mice, diabetic SAMP8 mice exhibited increased cerebral amyloid-β, dysregulated tau-phosphorylating glycogen synthase kinase 3β, reduced synaptophysin immunoreactivity, and displayed memory deficits, indicating Alzheimer-like changes. High fat diet-induced type 2 diabetic SAMP8 mice may represent the metabolic model of AD

Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment

Cognitive impairment, associated with ageing, stress, hypertension and various neurodegenerative disorders including Parkinson’s disease and epilepsy, is a major health issue. The present review focuses on Alzheimer’s disease (AD), since it is the most important cause of cognitive impairment. It is characterized by progressive memory loss, language deficits, depression, agitation, mood disturbances and psychosis. Although the hallmarks of AD are cholinergic dysfunction, β-amyloid plaques and neurofibrillary tangle formation, it is also associated with derangement of other neurotransmitters, elevated levels of advanced glycation end products, oxidative damage, neuroinflammation, genetic and environmental factors. On one hand, this complex etiopathology makes a response to commonly used drugs such as donepezil, rivastigmine, galantamine and memantine less predictable and often unsatisfactory. On the other hand, it supports the use of herbal medicines due to their nonspecific antioxidant and anti-inflammatory activity and specific cholinesterase inhibitory activity. The popularity of herbal medicines is also increasing due to their perceived effectiveness, safety and affordability. In the present article, the experimental and clinical evidence have been reviewed for various Indian herbal medicines such as Centella asiatica, Bacopa monnieri, Curcuma longa, Clitoria ternatea, Withania somnifera, Celastrus paniculatus, Evolvulus alsinoides, Desmodium gangeticum, Eclipta alba, Moringa oleifera and Convolvulus pluricaulis, which have shown potential in cognitive impairment. Some commonly available herbal formulations for memory impairment in India have also been reviewed

Indian medicinal herbs and formulations for Alzheimer\u27s disease, from traditional knowledge to scientific assessment

Cognitive impairment, associated with ageing, stress, hypertension and various neurodegenerative disorders including Parkinson\u27s disease and epilepsy, is a major health issue. The present review focuses on Alzheimer\u27s disease (AD), since it is the most important cause of cognitive impairment. It is characterized by progressive memory loss, language deficits, depression, agitation, mood disturbances and psychosis. Although the hallmarks of AD are cholinergic dysfunction, β-amyloid plaques and neurofibrillary tangle formation, it is also associated with derangement of other neurotransmitters, elevated levels of advanced glycation end products, oxidative damage, neuroinflammation, genetic and environmental factors. On one hand, this complex etiopathology makes a response to commonly used drugs such as donepezil, rivastigmine, galantamine and memantine less predictable and often unsatisfactory. On the other hand, it supports the use of herbal medicines due to their nonspecific antioxidant and anti-inflammatory activity and specific cholinesterase inhibitory activity. The popularity of herbal medicines is also increasing due to their perceived effectiveness, safety and affordability. In the present article, the experimental and clinical evidence have been reviewed for various Indian herbal medicines such a

Anti-oxidant and Anti-inflammatory activity of <i>Safoof</i> <i>Mohazzil</i>: A traditional, Poly-herbal Unani formulation for Obesity

461-465Inflammation and oxidative stress have been reported in obesity. Safoof Mohazzil, is a traditional formulation prescribed by Unani physicians for weight loss. In the present study, antioxidant and anti-inflammatory properties of Safoof Mohazzil were evaluated using pyrogallol induced hepatotoxicity and carrageenan induced paw edema, respectively, in male Wistar rats. For the antioxidant study, rats were treated with Safoof Mohazzil for 14 days at the doses of 250, 500 and 1000 mg/kg, p.o. On 14th day, 2 hrs after the last dose of Unani formulation, pyrogallol (100 mg/kg) was injected intraperitoneally and on next day the animals were sacrificed for estimation of hepatic oxidative stress markers (malondialdehyde and reduced glutathione). Safoof Mohazzil demonstrated dose-dependent anti-oxidant activity. To assess its anti-inflammatory property, Safoof Mohazzil was administered at the doses of 500 & 1000 mg/kg, p.o. for 7 days and on 7th day carrageenan was administered 1 hr after the last dose of Unani formulation. The change in paw volume was calculated at 1, 3 and 6 hrs. Significant anti-inflammatory activity was found at 1000 mg/kg dose which is the human equivalent of its anti-obesity dose. The antioxidant and anti-inflammatory activity of Safoof Mohazzil support its use in obesity and possibly metabolic syndrome

Corticosterone response to gestational stress and postpartum memory function in mice - Fig 2

<p>The Morris water task (MWT): A) The swim time (sec) across the 8 days of training in the three groups. B) The swim time average in the three groups (○: control group, Δ: physical stress (PS) group, □: noise stress (NS) group). A significantly higher swim time was observed in both stressed groups relative to the control group. C) The swim speed (m/s) during the 8 days of training in the three groups. D) The swim speed average in the three groups. A significantly lower swim speed was shown in both stressed groups compared with the control group. F) A significant difference was observed between the NS stress group and the control group in probe time (sec). The difference between time spent in the target quadrant and mean of time spent in other quadrants was significant in the three groups. N = 10 in the three groups. Results reported as mean ± S.E.M. Asterisks indicate *p<0.05 or **p<0.01.</p

Comparison between corticosterone levels on gestational days 11 and 17 in every group.

<p>Comparison between corticosterone levels on gestational days 11 and 17 in every group.</p