Neuroprotective effect of lacosamide on cognitive dysfunction in Streptozotocin induced Alzheimer disease

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Fatma Sobhy Ibrahim ◽  
Lobna Fouad Abdel-Aziz ◽  
Wesam Mostafa Elbakly ◽  
Nesreen Hamdy El Gayar
Keyword(s):  
Alzheimer Disease ◽  
Antiepileptic Drug ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Mrna Level ◽  
Memory Loss ◽  
Control Group ◽  
Histone Deacetylase Inhibition ◽  
Significant Prolongation ◽  
Y Maze

Abstract Alzheimer disease (AD) is a chronic and progressive neurodegenerative disorder characterized by memory loss and cognition impairment. A link has been established between AD and epilepsy sharing multiple mechanisms and pathogenesis. Similar Hippocampal changes have been found between both diseases. Choosing antiepileptic drug in AD patient represent a great a challenge especially with increase seizure risk in AD patients. Lacosamide, antiepileptic drug, was reported to have a neuroprotective effect in animal models and a histone deacetylase inhibition activity. This study was designed to investigate the potential effect of chronic lacosamide treatment in Streptozotocin induced AD in male Wistar rats. Methods AD animal model was induced with single bilateral intracerebroventricular injection of STZ (3 mg/kg) on day one. Lacosamide (30 mg/kg orally, once daily) was administrated for 21 days. Cognitive function assessment was done with Morris Water Maze (MWM) and Y Maze tasks. APP and MAPT mRNA level were measured. Results ICV-STZ caused significant prolongation in Escape latency time and reduction in time spent in target quadrant in MWM and reduction in spontaneous alteration ratio in Y Maze compared to control group. STZ induced Up-regulation in Amyloid precursor protein and Microtubule associated protein tau gene expression. Chronic Lacosamide treatment attenuated STZ induced cognitive impairment and mitigated APP and MAPT induced expression with STZ. Conclusion Lacosamide has a neuroprotective effect against STZ induced cognitive deficits ameliorating Aβ and Tau pathology.

scholarly journals Neuroprotective effect of pterostilbene on ketamine induced schizophrenia in mice

2016 ◽  
Vol 1 (03) ◽  
pp. 96-103 ◽  
Author(s):  
Vasudha Bakshi ◽  
Devender Palsa ◽  
Nazia Begum ◽  
Jeevan Kommidi ◽  
Kapishwar Singh ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Open Field ◽  
Forced Swim Test ◽  
Neuroprotective Effect ◽  
Oxidant Stress ◽  
Acetylcholinesterase Activity ◽  
Control Group ◽  
Swim Test ◽  
Forced Swim ◽  
Y Maze

Objective: The aim of this study is to investigate the effects of pterostilbene on the behavior of mice and oxidative stress under the influence of Ketamine induced schizophrenia model. Methods: Schizophrenia was induced in mice by ketamine (50mg/kg/day, i.p, for 14 days). The treatment effect of pterostilbene (10 and 20 mg/kg/day, p.o, for 14 days) were verified on Actophotometer, Y-maze, Forced swim test (FST), open field apparatus, acetylcholinesterase activity and anti oxidant stress-related biomarker (Catalase, GSH, TBARS, SOD) levels in brain tissues. Results: Pterostilbene decreased TBARS, AChE and increased SOD, CAT, GSH levels in mice brain when compared with control group. It also improved spatial recognition memory, decreased mobility time, decreased exploratory behaviour and locomotor activity as evident by improved performance in Y-Maze task, Forced swim test, Open field test and Locomotor activity test. Conclusion: Pterostilbene has a neuroprotective role related atleast in part to an antioxidant mechanism and Anti AChE activity, which could be explored as more effective therapies of schizophrenia and other psychiatric diseases.

scholarly journals EFFECT OF SESAMOL IN ASSOCIATION WITH FOLIC ACID ON 6-OHDA INDUCED PARKINSONIAN ANIMALS- BIOCHEMICAL, NEUROCHEMICAL AND HISTOPATHOLOGICAL EVIDENCE

2017 ◽  
Vol 10 (4) ◽  
pp. 46 ◽  
Author(s):  
Khadira Sereen ◽  
Vijayalakshmi K ◽  
Priya Nagappan ◽  
Shinu Balima
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Folic Acid ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Biochemical Parameter ◽  
Lesion Group ◽  
Control Group ◽  
Tbars Level ◽  
6 Hydroxydopamine

Objective: Parkinson’s disease (PD) is the world’s second neurodegenerative disorder. Degeneration of dopaminergic neurons is the hallmark of the disease. Here is a novel approach to treat PD with a phenolic compound Sesamol (SA) and in combination with Folic acid (FA).Methods: The study was designed with five groups of animals and 6 rats in each group. The rats was infused with 6-hydroxydopamine (10μg/2μl in 0.1% ascorbic acid saline) once for the development of PD, Group 1(control), Group 2(Lesion), Group 3(Lesion+ SA), Group 4(Lesion + SA+ FA) and Group 5(Lesion+ L-dopa). The biochemical parameter like glucose, triglycerides, protein, folic acid, TBARS and antioxidant profile in serum were estimated. The neurotransmitters level in striatum was estimated and histopathology of striatum and mid-brain tissues was carried out.Results: The results showed that 6-hydroxydopamine induced lesion has a significant alteration in the level of glucose, triglycerides, protein and folic acid where as TBARS level was elevated and the activities of antioxidants and neurotransmitters level were reduced. This was significantly restored on SA+FA treatment. The lesion group shows an abnormal architecture of striatum and mid-brain, whereas on SA+FA treatment there was minimal abnormality.Conclusion: Thus our study demonstrates that Sesamol has neuroprotective effect against 6-hydroxy dopamine insult and showed a synergic effect when combined with Folic acid.Keywords: Parkinson’s disease, Sesamol, Folic acid, 6-Hydroxy dopamine, Neurotransmitter, Antioxidant

Neuroprotective Effect of Nilotinib on Cortical Pyramidal Cells, Histological, Morphometric and Biochemical Study

2020 ◽  
pp. 23-33
Author(s):  
Ahmed S. Ahmed
Keyword(s):  
Cell Death ◽  
Antioxidant Enzymes ◽  
Antiepileptic Drug ◽  
Neuroprotective Effect ◽  
Latency Period ◽  
Neuronal Cell ◽  
Pyramidal Cells ◽  
Male Rats ◽  
Control Group ◽  
Cortical Tissue

Introduction: Death of neuronal cell and gliosis are the two main pathological hallmarks induced by nervous tissue stress like conditions such as status epilepticus. Previous studies have mentioned that neuronal cell death occur as a result of different mechanisms, namely, necrosis and apoptosis. Although more recent studies have explained the cell death on the basis of autophagy. Many antiepileptic drugs are marketed, taking into consideration the antioxidant role of nilotinib and support its use as a favorable antiepileptic drug. The aim of the present study is to assess the neuroprotective effect of antiepileptic drug nilotinib on cortical tissue in rats. Materials and Methods: Sixty adult male rats were divided into three groups: (1) Control group, (2) pentylenetetrazol group (injected with pentylenetetrazol 60 mg/kg, subcutaneously), (3) nilotinib and pentylenetetrazol group (pretreated with nilotinib, 25 mg/kg daily for seven days prior to pentylenetetrazol administration). Latency of seizure and level of either oxidant or antioxidant enzymes in the cortical tissue was assessed. The histopathological changes in the cerebral cortex were studied also using hematoxylin and eosin stain. Results: Nilotinib increased the latency period of convulsions, increased the antioxidant enzymes levels with regain of the normal histological features. Conclusions: Nilotinib proved to promote the antioxidant, antiapoptotic pathways, anti-inflammatory and inhibiting autophagy which favor its use as an anti-epileptic drug.

scholarly journals Behavioral, Biochemical and Histopathological effects of Standardised Pomegranate extract with Vinpocetine, Propolis or Cocoa in a rat model of Parkinson’s disease

2020 ◽  
Author(s):  
Azza A. Ali ◽  
Mona M. Kamal ◽  
Mona G. Khalil ◽  
Shimaa A. Ali ◽  
Hemat A. Elariny ◽  
...  
Keyword(s):  
Rat Model ◽  
Caspase 3 ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Acetylcholinesterase Activity ◽  
Brain Regions ◽  
Y Maze ◽  
Tnf Α ◽  
Locomotor Activities ◽  
Histopathological Effects

AbstractIntroductionParkinsonism is a neurodegenerative disorder. Pomegranate (POM) has been previously shown to have a dopaminergic neuroprotective effect against Parkinsonism.ObjectiveThe aim of the current study is to compare the efficacy of POM, vinpocetine, Propolis, Cocoa or L-dopa using RT-induced Parkinsonism rat model.MethodsRats were divided into seven groups; one normal and five RT model groups. One of the RT (2.5 mg/kg sc) groups served as non-treated parkinsonism model whereas the others were treated with either L-dopa (10 mg/kg PO) or with POM (150 mg/kg PO) together with each of the following; vinpocetine (VIN) (20 mg/kg PO), Propolis (300 mg/kg PO), Cocoa (24 mg/kg PO). Motor and cognitive performances were examined using three tests (catalepsy, open-field, Y-maze). Striatal dopamine, norepinephrine, serotonin, acetylcholinesterase, GABA, Glutamate, GSK 3B, BDNF levels were assessed as well as MDA, SOD, TAC, IL-1β, TNF-α, iNOs and caspase-3. Also, histopathological examinations of different brain regions were determined.ResultsTreatment with L-dopa alone or with all POM combination groups alleviated the deficits in locomotor activities, cognition, monoamine levels, acetylcholinesterase activity, oxidative stress, and inflammatory markers as well as caspase-3 expression induced by RT.ConclusionCombinations of POM with each of VIN, Propolis or Cocoa have a promising disease-modifying antiparkinsonian therapy even without being given as an adjuvant to L-dopa.

scholarly journals The Neuroprotective Effect of L-Carnitine against Glyceraldehyde-Induced Metabolic Impairment: Possible Implications in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2109
Author(s):  
Simona Magi ◽  
Alessandra Preziuso ◽  
Silvia Piccirillo ◽  
Francesca Giampieri ◽  
Danila Cianciosi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Survival ◽  
Mitochondrial Function ◽  
Cortical Neurons ◽  
Neurodegenerative Disorder ◽  
Neuronal Damage ◽  
Mitochondrial Dynamics ◽  
Neuroprotective Effect ◽  
Memory Loss

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive regression and memory loss. Dysfunctions of both glucose metabolism and mitochondrial dynamics have been recognized as the main upstream events of the degenerative processes leading to AD. It has been recently found that correcting cell metabolism by providing alternative substrates can prevent neuronal injury by retaining mitochondrial function and reducing AD marker levels. Here, we induced an AD-like phenotype by using the glycolysis inhibitor glyceraldehyde (GA) and explored whether L-carnitine (4-N-trimethylamino-3-hydroxybutyric acid, LC) could mitigate neuronal damage, both in SH-SY5Y neuroblastoma cells and in rat primary cortical neurons. We have already reported that GA significantly modified AD marker levels; here we demonstrated that GA dramatically compromised cellular bioenergetic status, as revealed by glycolysis and oxygen consumption rate (OCR) evaluation. We found that LC ameliorated cell survival, improved OCR and ATP synthesis, prevented the loss of the mitochondrial membrane potential (Δψm) and reduced the formation of reactive oxygen species (ROS). Of note, the beneficial effect of LC did not rely on the glycolytic pathway rescue. Finally, we noticed that LC significantly reduced the increase in pTau levels induced by GA. Overall, these findings suggest that the use of LC can promote cell survival in the setting of the metabolic impairments commonly observed in AD. Our data suggest that LC may act by maintaining mitochondrial function and by reducing the pTau level.

scholarly journals Diuretics: A possible keystone in upholding cognitive health

2018 ◽  
Vol 8 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Tyler DeLoach ◽  
Jennifer Beall
Keyword(s):  
Alzheimer Disease ◽  
Risk Reduction ◽  
Disease Risk ◽  
Neuroprotective Effect ◽  
Memory Loss ◽  
Antihypertensive Agents ◽  
Hazard Ratio ◽  
Inverse Association ◽  
Drug Classes ◽  
Incident Rate

Abstract Introduction: Dementia encompasses diseases of progressive memory loss and neurological alterations, including Alzheimer disease. Hypertension is one risk factor proposed for development of Alzheimer disease. The objective is to evaluate the current literature for use of diuretics in the prevention of dementia. Methods: Literature was not considered if published before January 1, 2000, or after May 31, 2015. PubMed was used to locate sources. Four search terms were used to find data: Alzheimer disease, antihypertensive agents, diuretics, and dementia. Results: Four studies of efficacy of diuretic usage in the prevention against dementia met criteria. Potassium-sparing diuretics displayed risk reduction of Alzheimer disease and maintenance of cognitive function. Risk reduction was demonstrated when used alone (adjusted hazard ratio [aHR] 0.09, 95% confidence interval [CI] 0.01-0.41) as compared to use of other antihypertensives without potassium-sparing diuretics (aHR 0.76, 95% CI 0.49-1.15). Other antihypertensive drug classes did show some benefit, however. Diuretic and angiotensin receptor blocker users had a lower Alzheimer disease risk versus those with no antihypertensive use (hazard ratio 0.40, 95% CI 0.26-0.61) and (hazard ratio 0.37, 95% CI 0.19-0.72), respectively. Additionally, thiazide diuretics were also shown to reduce Alzheimer risk. Thiazide and potassium-sparing combination significantly reduced risk versus non-antihypertensive users (aHR 0.63, 95% CI 0.42-0.94). Discussion: Available research demonstrates an inverse association between diuretic use and the incident rate of dementia. Specifically, this has been found with thiazide and potassium-sparing diuretics when used alone or in combination. This review suggests that patients receiving diuretics for hypertension may receive an added neuroprotective effect.

scholarly journals Effect of Metformin on Some Cognitive Functions in Old Rats

2020 ◽  
Author(s):  
Mohammad Pak-Hashemi ◽  
Mahsa Hassanipour ◽  
Ayat Kaeidi ◽  
Pooya Saeed-Askari ◽  
Iman Fatemi ◽  
...  
Keyword(s):  
Memory Loss ◽  
Male Rats ◽  
Control Group ◽  
Elderly Male ◽  
Complex Process ◽  
Y Maze ◽  
Plus Maze ◽  
Old Rats ◽  
Neurological Effects ◽  
Post Hoc

Introduction: Aging is a complex process and is considered as a risk factor for many diseases such as hypertension, Alzheimer, cancer, depression and anxiety. Recently, it has been shown that metformin, an anti-diabetic drug, has important neurological effects such as preventing memory loss, stroke, anxiety, inflammation and seizures. Therefore, the aim of this study was investigating the effects of metformin on some cognitive factors in elderly male rats. Methods: 24 rats (22 months) were randomly divided into 3 groups (n=8). The first group was the control group that received water orally, the second group received metformin 1 mg/kg orally and the third group received metformin 10 mg/kg orally. After treatment for 40 days (once daily), behavioral tests, including Y-maze, elevated plus maze and depression test were performed on animals. Results were analyzed using GraphPad Prism version 6 and One-way ANOVA followed by Tukey-post hoc test. Results: The results of this study showed that metformin at a dose of 10 mg/kg significantly reduced anxiety (P<0.001) and depression (P<0.001) in older animals. Metformin at a dose of 1 mg/kg failed to improve aging-related disorders in this model. Conclusion: Metformin at a dose of 10 mg/kg can reduce the quality of life by reducing anxiety and depression.

scholarly journals Neuroprotective Effect of Gallic Acid on Memory Deficit and Content of BDNF in Brain Entorhinal Cortex of Rat’s Offspring in Uteroplacental Insufficiency Model

2020 ◽  
Author(s):  
Zahra Esfandiari ◽  
Mohammad Amin Edalatmanesh
Keyword(s):  
Gallic Acid ◽  
Entorhinal Cortex ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Memory Deficit ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Y Maze ◽  
Spss Software ◽  
Post Hoc

Introduction: Uteroplacental insufficiency (UPI) causes neurodevelopmental deficits affecting the intrauterine growth restricted (IUGR) offspring. This study aimed to analyze the effects of Gallic acid (GA) on memory deficit and brain-derived neurotrophic factor (BDNF) content in entorhinal cortex of UPI rat models. Methods: In this experimental study, 40 pregnant Wistar rats were randomly divided into 5 groups, including: control, UPI, UPI+GA100, UPI+GA200and UPI+GA400. For IUGR induction, anterior uterine artery occlusion surgery was carried out on gestation day (GD) 18. From GD15, GA was administrated orally, in 100, 200 and 400 mg/kg BW doses until the birth of their neonates. Spatial and working memories are analyzed by Morris water maze and Y maze at postnatal day (PND) 30, respectively. Then, BDNF cerebral cortex level was estimated using ELISA technique.The data were analyzed through ANOVA and Tukey Post hoc in SPSS software version 16. Results: A significant decrease was observed in spatial and working memories and BDNF content in entorhinal cortex of UPI group in comparison with the control group (p˂0.05). On the other hand, GA-treated groups showed a significant increase in BDNF content and amelioration of spatial and working memories (p˂0.05). Conclusion: Fetal growth restrictionafter UPI by decreasingBDNFlevel in entorhinal cortex caused memory deficits in rat’s model. Moreover, neuroprotective effects of GA lead to increased BDNF content and ameliorate cognitive deficits in UPI model.

scholarly journals (-)-cis-Carveol, a Natural Compound, Improves β-Amyloid-Peptide 1-42-Induced Memory Impairment and Oxidative Stress in the Rat Hippocampus

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Lucian Hritcu ◽  
Razvan Stefan Boiangiu ◽  
Mayara Castro de Morais ◽  
Damião Pergentino de Sousa
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Amyloid Peptide ◽  
Radial Arm Maze ◽  
Reference Drug ◽  
Y Maze ◽  
Group A ◽  
Biochemical Analyses

Alzheimer’s disease (AD) could be considered a multifactorial neurodegenerative disorder characterized by the accumulation of the β-amyloid-peptide (Aβ) within the brain leading to cognitive deficits, oxidative stress, and neuroinflammation. The present work was carried out to investigate the neuroprotective effect of (-)-cis-carveol (1% and 3%, for 21 days) against the β-amyloid-peptide 1-42- (Aβ1-42-) induced AD. Twenty-five rats were divided into five groups (n=5/group): the first group—control (sham-operated); the second group—Aβ1-42 (1 mM) that received donepezil treatment (5 mg/kg, as the positive reference drug in the Y-maze and the radial arm maze tests); the third group—Aβ1-42 (1 mM); the fourth and fifth groups—Aβ1-42 (1 mM) that received (-)-cis-carveol treatment groups (1% and 3%). The results of this study demonstrated that (-)-cis-carveol improved Aβ1-42-induced memory deficits examined by using Y-maze and radial arm maze in vivo tests. Also, the biochemical analyses of the hippocampus homogenates showed that (-)-cis-carveol reduced hippocampal oxidative stress caused by Aβ1-42. Our results suggested that the use of (-)-cis-carveol may be suitable for decreasing AD-related symptoms.

Protective Effect of Boswellic Resin Against Memory Loss and Alzheimer’s Induced by Aluminum Tetrachloride and D-Galactose (Experimental study in Mice)

2020 ◽  
Author(s):  
K. Zerrouki ◽  
N. Djebli ◽  
L. Gadouche ◽  
I. Erdogan Orhan ◽  
F. SezerSenol Deniz ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Protective Effect ◽  
Cell Damage ◽  
Memory Loss ◽  
Control Group ◽  
Total Extract ◽  
Swiss Mice ◽  
Octyl Acetate

Nowadays, because of the industrialization, a lot of contaminant were available ; the consequences of this availability are apparition of diseases including neurodegeneration. Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. This study is based on the effect of the Boswellic resin, which is from a medicinal plant and known for its antioxidant effects on nerve cell damage. The objective of this work was to evaluate the in vitro and in vivo effects of the Boswellic resin on anticholinesterase activity and Alzheimer’s disease (AD) induced by D-galactose and aluminum tetrachloride in Swiss mice. Chemical composition of the resin essential oil was identified by the CG-MS analysis. The antioxidant activity was also assessed by the DMPD and metal chelation methods. In order to understand the mechanism of memory improvement, the acetylcholinesterase, AChE, and butyrylcholinesterase, BChE, inhibitory assays were performed. In vivo part of the study was achieved on Swiss mice divided into four groups: control, AD model, treated AD, and treated control group. The identification of chemical composition by CG-MS reach the 89.67% of the total extract compounds presented some very important molecules (p-Cymene, n-Octyl acetate, α-Pinene…). The present study proves that Boswellic resin improves memory and learning in treated Alzheimer’s group, modulates the oxidative stress and be involved in the protective effect against amyloid deposition and neurodegeneration, and stimulates the immune system in mice’s brain.

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