scholarly journals Tamoxifen Application Is Associated with Transiently Increased Loss of Hippocampal Neurons Following Virus Infection

2021 ◽  
Vol 22 (16) ◽  
pp. 8486
Author(s):  
Kirsten Hülskötter ◽  
Fred Lühder ◽  
Alexander Flügel ◽  
Vanessa Herder ◽  
Wolfgang Baumgärtner
Keyword(s):  
Hippocampal Neurons ◽  
Negative Impact ◽  
Neuronal Loss ◽  
Antigen Expression ◽  
High Dose ◽  
Hippocampal Damage ◽  
Virus Elimination ◽  
Neuroprotective Effects ◽  
Reactive Astrogliosis ◽  
T Cell Infiltration

Tamoxifen is frequently used in murine knockout systems with CreER/LoxP. Besides possible neuroprotective effects, tamoxifen is described as having a negative impact on adult neurogenesis. The present study investigated the effect of a high-dose tamoxifen application on Theiler’s murine encephalomyelitis virus (TMEV)-induced hippocampal damage. Two weeks after TMEV infection, 42% of the untreated TMEV-infected mice were affected by marked inflammation with neuronal loss, whereas 58% exhibited minor inflammation without neuronal loss. Irrespective of the presence of neuronal loss, untreated mice lacked TMEV antigen expression within the hippocampus at 14 days post-infection (dpi). Interestingly, tamoxifen application 0, 2 and 4, or 5, 7 and 9 dpi decelerated virus elimination and markedly increased neuronal loss to 94%, associated with increased reactive astrogliosis at 14 dpi. T cell infiltration, microgliosis and expression of water channels were similar within the inflammatory lesions, regardless of tamoxifen application. Applied at 0, 2 and 4 dpi, tamoxifen had a negative impact on the number of doublecortin (DCX)-positive cells within the dentate gyrus (DG) at 14 dpi, without a long-lasting effect on neuronal loss at 147 dpi. Thus, tamoxifen application during a TMEV infection is associated with transiently increased neuronal loss in the hippocampus, increased reactive astrogliosis and decreased neurogenesis in the DG.

Effect of feeding with bilberry fruit on the expression pattern of αCaMKII in hippocampal neurons in normal and diabetic rats

2017 ◽  
Vol 20 (2) ◽  
pp. 313-319 ◽  
Author(s):  
M. Matysek ◽  
S. Mozel ◽  
R. Szalak ◽  
A. Zacharko-Siembida ◽  
K. Obszańska ◽  
...  
Keyword(s):  
Cognitive Processes ◽  
Hippocampal Neurons ◽  
Negative Impact ◽  
Expression Patterns ◽  
Memory Loss ◽  
Diabetic Rats ◽  
Control Group ◽  
Neuroprotective Effects ◽  
The Central Nervous System ◽  
And Control

Abstract αCaMKII, widely occurring in the central nervous system, plays a significant role in cognitive processes. It is well known that diabetes is a risk factor that may trigger brain atrophy, cognitive dysfunction and finally lead to memory loss. Antioxidants richly present in bilberry fruits are believed to have significant effects on diabetes-related brain dysfunctions mainly due to their abilities to modulate neurotransmitter release that lead to reduction of the negative impact of free radicals on cognitive processes. The aim of the present research was to immunohistochemically investigate the expression patterns of αCaMKII in hippocampal neurons from non-diabetic, diabetic and diabetic rats fed with an extract of bilberry fruit. The obtained results show that in comparison to the control group, in diabetic rats hippocampal neurons immunoreactive (ir) to αCaMKII were swollen and the lengths of the neuronal fibres were reduced. Further study shows that in diabetic rats fed with bilberry fruit, αCaMKII-positive nerve fibres were significantly longer when compared to the groups of diabetic and control rats. Additionally, we observed statistically significant changes in the average larger diameter of αCaMKII-ir hippocampal neurons between groups of diabetic rats (with vs. without supplement of bilberry fruit). The results of the present work suggest that antioxidants present in bilberry fruits influence the morphology of and possibly exhibit beneficial and neuroprotective effects on hippocampal neurons during diabetes. It is likely that changes in the appearance of αCaMKII-expressed hippocampal neurons may reflect the diabetes-evoked rise in Ca2+ level in the cerebral nerve terminals. The present research extends our knowledge of preventive mechanisms for cognitive dysfunctions occurring in the brain during diabetes.

scholarly journals Hippocampal Neurons Become More Vulnerable to Glutamate after Subcritical Hypoxia: An in vitro Study

1990 ◽  
Vol 10 (6) ◽  
pp. 877-884 ◽  
Author(s):  
Eiji Kohmura ◽  
Kazuo Yamada ◽  
Toru Hayakawa ◽  
Akira Kinoshita ◽  
Katsumi Matsumoto ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Hippocampal Neurons ◽  
Neuronal Loss ◽  
In Vitro Study ◽  
Defined Medium ◽  
High Dose ◽  
Mk 801 ◽  
Plating Density ◽  
Increased Susceptibility

The neurotoxicity of glutamate and hypoxia was investigated in vitro on hippocampal neurons, which were obtained from 18-day-old rat fetuses and were maintained for 3 days in culture. Chemically defined medium without glutamate was used and the plating density was low enough that the effect of exogenously added glutamate could be directly evaluated. In the normal culture condition 1 m M glutamate was necessary to cause significant neuronal loss in the following 24 h. In marked contrast, when glutamate was added after subcritical hypoxic stress, a dose of glutamate as low as 10 μ M could exhibit neurotoxicity. Administration of MK-801, a selective noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, could in part reverse this increased susceptibility to low-dose glutamate after hypoxia, although MK-801 could not protect hippocampal neurons from high-dose glutamate. Therefore, both the NMDA receptor and other subclasses of the glutamate receptor may be involved in this neurotoxicity of glutamate. Different mechanisms of glutamate neurotoxicity with high and low doses are discussed. Our results showed that hippocampal neurons exposed to subcritical hypoxia become more vulnerable to glutamate than those without hypoxia. This increased susceptibility is of great interest to understanding the mechanism of slowly ongoing neuronal loss caused by ischemia or epilepsy.

scholarly journals Neuroprotective Effects of Lycium Barbarum Berry on Neurobehavioral Changes and Neuronal Loss in the Hippocampus of Mice Exposed to Acute Ionizing Radiation

2021 ◽  
Author(s):  
Lei Guo ◽  
Qian-Qian Du ◽  
Piao-Qin Cheng ◽  
Ting-Ting Yang ◽  
Chao-Qun Xing ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Dentate Gyrus ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Food Supplement ◽  
Lycium Barbarum ◽  
Neuroprotective Effects ◽  
Neuron Loss ◽  
Radiation Induced

Abstract Background: Brain exposure to ionizing radiation during the radiotherapy of brain tumor or metastasis of peripheral cancer cells to the brain has resulted in cognitive dysfunction by reducing neurogenesis in hippocampus. Methods: To demonstrate the radioprotective effect of lycium barbarum berry extract (Lyc), we evaluated the neurobehavioral alterations and the numbers of NeuN, calbindin (CB) and parvalbumin (PV) immunopositive hippocampal neurons in BALB/c mice after acute 5.5 Gy radiation with/without oral administration of Lyc at the dosage of 10 g/kg daily for 4 weeks. Results: The results showed that Lyc could improve irradiation-induced animal weight loss, depressive behaviors, spatial memory impairment and hippocampal neuron loss. Immunohistochemistry study demonstrated that the loss of NeuN-immunopositive neuron in the hilus of the dentate gyrus, CB-immunopositive neuron in CA1 strata radiatum, lacunosum moleculare and oriens, and PV-positive neuron in CA1 stratum pyramidum and stratum granulosum of the dentate gyrus after irradiation were significantly improved by Lyc treatment. Conclusions: The neuroprotective effect of Lyc on those hippocampal neurons may benefit the configuration of learning related neuronal networks and then improve radiation induced neurobehavioral changes such as cognitive impairment and depression. It suggests that lycium barbarum berry may be used as a potential radio-neuro-protective food supplement to prevent ionizing radiation induced neuron loss and neuropsychological disorders.

scholarly journals Amphiphilic Nanocarrier Systems for Curcumin Delivery in Neurodegenerative Disorders

Medicines ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 126 ◽  
Author(s):  
Miora Rakotoarisoa ◽  
Angelina Angelova
Keyword(s):  
Neurodegenerative Disorders ◽  
Liquid Crystalline ◽  
Water Solubility ◽  
Neuronal Loss ◽  
Drug Solubility ◽  
Neuroprotective Effects ◽  
Slowing Down ◽  
Combination Treatments ◽  
Physico Chemical ◽  
Lateral Sclerosis

Neurodegenerative diseases have become a major challenge for public health because of their incurable status. Soft nanotechnology provides potential for slowing down the progression of neurodegenerative disorders by using innovative formulations of neuroprotective antioxidants like curcumin, resveratrol, vitamin E, rosmarinic acid, 7,8-dihydroxyflavone, coenzyme Q10, and fish oil. Curcumin is a natural, liposoluble compound, which is of considerable interest for nanomedicine development in combination therapies. The neuroprotective effects of combination treatments can involve restorative mechanisms against oxidative stress, mitochondrial dysfunction, inflammation, and protein aggregation. Despite the anti-amyloid and anti-tau potential of curcumin and its neurogenesis-stimulating properties, the utilization of this antioxidant as a drug in neuroregenerative therapies has huge limitations due to its poor water solubility, physico-chemical instability, and low oral bioavailability. We highlight the developments of soft lipid- and polymer-based delivery carriers of curcumin, which help improve the drug solubility and stability. We specifically focus on amphiphilic liquid crystalline nanocarriers (cubosome, hexosome, spongosome, and liposome particles) for the encapsulation of curcumin with the purpose of halting the progressive neuronal loss in Alzheimer’s, Parkinson’s, and Huntington’s diseases and amyotrophic lateral sclerosis (ALS).

scholarly journals The Dose-dependent Dual Effects of Corticosterone on Spatial Memory Ability After Traumatic Brain Injury Are Mediated by Two Corticosteroid Receptor Systems

2021 ◽  
Author(s):  
Bin Zhang ◽  
Mengshi Yang ◽  
Qiongyu Yan ◽  
Xiaojian Xu ◽  
Fei Niu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Spatial Memory ◽  
Signaling Pathways ◽  
Hippocampal Neurons ◽  
High Dose ◽  
Short Term ◽  
Memory Ability ◽  
Neurotoxic Effects ◽  
Dose Dependent

Abstract Background: Our recent studies reported the opposite effects of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) on neuron survival after traumatic brain injury (TBI). However, as a mixed agonist for MR and GR, whether short term use of high-dose endogenous glucocorticoids exerts neurotoxic effects by excessive activation of GR, what is the set-point, and the possible signaling pathways remain unclear. This study examined the dose-dependent dual effects of corticosterone (CORT) on the spatial memory, the survival of hippocampal neurons and the possible receptor-mediated downstream signaling pathways after TBI.Methods: Based on controlled cortical impact (CCI) and CORT treatments, Sprague-Dawley rats (n=168) were randomly divided into the sham, CCI, CCI + CORT1 (0.3 mg/kg), CCI + CORT2 (3 mg/kg), CCI + CORT3 (30 mg/kg), CCI + CORT1 + spirolactone (spirolactone: 50 mg/kg/d), and CCI + CORT3 + RU486 (RU486: 50 mg/kg/d) groups. Brain tissues were collected on postinjury day 3 and processed for histology and western blot analysis.Results: On postinjury day 3, we tested the learning and memory ability, neuronal apoptosis in the hippocampus, activation levels of MR and GR, Bcl-2 family proteins, and apoptosis-related intracellular signaling pathways. We found that different doses of CORT exhibited dual effects on the survival of hippocampal neurons and the spatial memory. Lower doses of CORT (0.3, 3 mg/kg) significantly increased the activation of MR, upregulated the phosphorylation of Akt/CREB/Bad and the Bcl-2 expression, reduced the number of apoptotic neurons, and subsequently improved the spatial memory. In contrast, higher dose of CORT (30 mg/kg) exerted opposite effect by over activating GR, upregulating the expressions of P53/Bax, and inhibiting the Erk/CREB activities. Conclusion: The results suggest that there is a threshold between the neuroprotective and neurotoxic effects of endogenous GC, higher dose of which, even for short-term use, should also be avoided after TBI.

Abstract TMP48: Effect of Pre-Morbid Antianxiety and Antidepressant Medications on Ischemic Stroke Functional Outcome

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Cecilia Peterson ◽  
Ka-Ho Wong ◽  
Michael Dela Cruz ◽  
Kirby Taylor ◽  
Jennifer J Majersik ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Regression Models ◽  
Primary Outcome ◽  
Negative Impact ◽  
Secondary Analysis ◽  
Anxiety And Depression ◽  
Neuroprotective Effects ◽  
Logistic Regression Models ◽  
Antidepressant Medications

Introduction: Antianxiety and antidepressant medications have shown some neuroprotective effects following stroke. However, the effect of premorbid use of these medications remains unclear. Hypothesis: Pre-morbid exposure to antianxiety or antidepressant medications will negatively impact recovery from acute ischemic stroke, measured by modified Rankin scale (mRS) at 90 days after stroke onset. Methods: This is a secondary analysis of the Albumin in Acute Ischemic Stroke (ALIAS) 2 trial. The primary outcome is 90-day mRS 0-1. The exposure is premorbid antidepressant or antianxiety medication. We fit univariate and multivariate logistic regression models to our outcome, with covariates chosen using a stepwise backwards interactive selection. Results: We included 806 patients with a mean (SD) age of 64.4 (12.8) years. The median (IQR) NIH Stroke Scale was 11 (8, 17) and 54.3% were male, 75.6% were Caucasian, 88.8% received tPA, 72.5% had hypertension, and 20.3% had diabetes. A total of 140/806 (17.4%) of patients took either an antidepressant or antianxiety medication, of which 91 took an antidepressant, 34 took an antianxiety medication, and 15 took both. The median (IQR) mRS Scale was one point higher in patients on antidepressant or antianxiety medication pre-stroke (3 vs. 2, p=0.019). The primary outcome of mRS 0-1 was seen in 37.7% of all patients. Taking an antidepressant or antianxiety medication was associated with lower odds of a good outcome in univariate (OR 0.61, 95% CI 0.41-0.91, p=0.015) and multivariate models (aOR 0.62, 95% CI 0.40-0.95, p=0.027) (Table 1). Conclusion: Pre-morbid exposure to antianxiety or antidepressant medications is associated with a worse outcome after acute ischemic stroke. This may be due to a negative impact of pre-stroke anxiety and depression that outweigh any neuroprotective factors of these medications.

scholarly journals Determining the Minimal Clinical Important Difference for Medication Quantification Scale III and Morphine Milligram Equivalents in Patients with Failed Back Surgery Syndrome

2020 ◽  
Vol 9 (11) ◽  
pp. 3747
Author(s):  
Lisa Goudman ◽  
Ann De Smedt ◽  
Patrice Forget ◽  
Maarten Moens
Keyword(s):  
Negative Impact ◽  
Treatment Success ◽  
Change Score ◽  
Failed Back Surgery Syndrome ◽  
Percentage Change ◽  
High Dose ◽  
Minimal Clinical Important Difference ◽  
A Value ◽  
Failed Back Surgery ◽  
Back Surgery

The Medication Quantification Scale III (MQS) is a tool to represent the negative impact of medication. A reduction in medication can serve as an indicator to evaluate treatment success. However, no cut-off value has yet been determined to evaluate whether a decrease in medication is clinically relevant. Therefore, the objective is to estimate the thresholds for the MQS and morphine milligram equivalents (MMEs) that best identify a clinically relevant important improvement for patients. Data from the Discover registry, in which patients with failed back surgery syndrome were treated with high-dose spinal cord stimulation, were used. Patient satisfaction was utilized to evaluate a clinically important outcome 12 months after stimulation. Anchor-based and distribution-based methods were applied to determine the minimal clinical important difference (MCID). Distribution-based methods revealed a value of 4.28 for the MQS and 33.61 for the MME as MCID. Anchor-based methods indicated a percentage change score of 41.2% for the MQS and 28.2% for the MME or an absolute change score of 4.72 for the MQS and 22.65 for the MME. For assessing a treatment outcome, we recommend using the percentage change score, which better reflects a clinically important outcome and is not severely influenced by high medication intake at baseline.

scholarly journals Neuroprotective Mechanisms of Resveratrol in Alzheimer’s Disease: Role of SIRT1

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Bruno Alexandre Quadros Gomes ◽  
João Paulo Bastos Silva ◽  
Camila Fernanda Rodrigues Romeiro ◽  
Sávio Monteiro dos Santos ◽  
Caroline Azulay Rodrigues ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Vital Role ◽  
Hippocampal Damage ◽  
Neuroprotective Effects ◽  
Amyloid A ◽  
Silent Information Regulator 1 ◽  
Anti Inflammatory

Alzheimer’s disease (AD) is a progressive and neurodegenerative disorder of the cortex and hippocampus, which eventually leads to cognitive impairment. Although the etiology of AD remains unclear, the presence ofβ-amyloid (Aβ) peptides in these learning and memory regions is a hallmark of AD. Therefore, the inhibition of Aβpeptide aggregation has been considered the primary therapeutic strategy for AD treatment. Many studies have shown that resveratrol has antioxidant, anti-inflammatory, and neuroprotective properties and can decrease the toxicity and aggregation of Aβpeptides in the hippocampus of AD patients, promote neurogenesis, and prevent hippocampal damage. In addition, the antioxidant activity of resveratrol plays an important role in neuronal differentiation through the activation of silent information regulator-1 (SIRT1). SIRT1 plays a vital role in the growth and differentiation of neurons and prevents the apoptotic death of these neurons by deacetylating and repressing p53 activity; however, the exact mechanisms remain unclear. Resveratrol also has anti-inflammatory effects as it suppresses M1 microglia activation, which is involved in the initiation of neurodegeneration, and promotes Th2 responses by increasing anti-inflammatory cytokines and SIRT1 expression. This review will focus on the antioxidant and anti-inflammatory neuroprotective effects of resveratrol, specifically on its role in SIRT1 and the association with AD pathophysiology.

scholarly journals Neuroprotective Effects of Grape Seed Procyanidins on Ethanol-Induced Injury and Oxidative Stress in Rat Hippocampal Neurons

2020 ◽  
Vol 55 (4) ◽  
pp. 357-366
Author(s):  
Wenyang Jin ◽  
Mizhu Sun ◽  
Bingbing Yuan ◽  
Runzhi Wang ◽  
Hongtao Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hippocampal Neurons ◽  
Primary Cultures ◽  
Neuronal Injury ◽  
Grape Seed ◽  
Neuroprotective Effects ◽  
Dendritic Length ◽  
New Type ◽  
The Brain ◽  
And Oxidative Stress

Abstract Aims Ethanol is a small molecule capable of interacting with numerous targets in the brain, the mechanisms of which are complex and still poorly understood. Studies have revealed that ethanol-induced hippocampal neuronal injury is associated with oxidative stress. Grape seed procyanidin (GSP) is a new type of antioxidant that is believed to scavenge free radicals and be anti-inflammatory. This study evaluated the ability and mechanism by which the GSP improves ethanol-induced hippocampal neuronal injury. Methods Primary cultures of hippocampal neurons were exposed to ethanol (11, 33 and 66 mM, 1, 4, 8, 12 and 24 h) and the neuroprotective effects of GSP were assessed by evaluating the activity of superoxide dismutase (SOD), the levels of malondialdehyde (MDA) and lactate dehydrogenase (LDH) and cell morphology. Results Our results indicated that GSP prevented ethanol-induced neuronal injury by reducing the levels of MDA and LDH, while increasing the activity of SOD. In addition, GSP increased the number of primary dendrites and total dendritic length per cell. Conclusion Together with previous findings, these results lend further support to the significance of developing GSP as a therapeutic tool for use in the treatment of alcohol use disorders.

scholarly journals NEUROPROTECTIVE EFFECTS OF AQUEOUS EXTRACT OF HYDROCOTYLE JAVANICA IN AMELIORATING NEUROBEHAVIORAL ALTERATION INDUCED BY MERCURY

2019 ◽  
Vol 12 (1) ◽  
pp. 374
Author(s):  
Pankaj Phukan ◽  
Sanjit Namasudra ◽  
Meenakshi Bawari ◽  
Mahuya Sengupta
Keyword(s):  
Locomotor Activity ◽  
Aqueous Extract ◽  
Mercuric Chloride ◽  
Path Length ◽  
Low Dose ◽  
Escape Latency ◽  
Learning Ability ◽  
High Dose ◽  
Neuroprotective Effects ◽  
Group I

Objective: This study aims to assess the effects of the aqueous extract of Hydrocotyle javanica (HJ) in ameliorating mercury-induced neurobehavioral toxicity.Methods: For the study, 36 adult male Swiss albino mice of 25–30 g in weight were taken. They were equally divided into six groups. Group I was treated with distilled water, Group II was treated with mercuric chloride (1.5 mg/kg), Group III was treated with HJ extract low dose (100 mg/kg), Group IV was treated with HJ extract high dose (200 mg/kg), Group V was treated with mercuric chloride plus HJ extract low dose, and Group VI was treated with mercuric chloride plus TB extract high dose. In all the groups, the doses were administered orally through oral gavage tube and the treatment lasted for 14 days. The behavioral effects evaluated were locomotor activity in the open field test, immobility in forced swimming test and anxiety in elevated plus maze test, spatial learning ability, and memory in the Morris water maze test.Results: The present study showed that mercury exposure significantly decreased the locomotor activity (p<0.001), number of annulus crossovers (p<0.001), number of open arm entries (p<0.01), time spent in open arms (p<0.001), and increased escape latency (p<0.01), path length (p<0.001), and immobility (p<0.001) in mice. The aqueous extract of HJ significantly alleviated the neurotoxic effects of mercury. The aqueous extract of HJ showed to increase the locomotor activity (p<0.01), number of annulus crossovers (p<0.001), number of open arm entries (p<0.05), and time spent in open arms (p<0.05), which was decreased in mercury-exposed mice. The HJ extract also showed to decrease the immobility (p<0.001), escape latency (p<0.05), and path length (p<0.001) in mercury-exposed mice.Conclusion: The result of the study shows that neurobehavioral changes induced by mercuric chloride were significantly reversed by the aqueous extract of HJ. Thus, base on the present study, it is concluded that HJ is effective in ameliorating the neurobehavioral deficits induced by mercury.

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