Effect of NMDAR-NMNAT1/2 pathway on neuronal cell damage and cognitive impairment of sevoflurane-induced aged rats

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

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Blood Pressure Profiles and Cognitive Function from Adulthood to Old Age: Chasing a Golden Middle Way?

Journal of Clinical Medicine ◽

10.3390/jcm10153243 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3243

Author(s):

Rita Del Pinto ◽

Davide Grassi ◽

Raffaella Bocale ◽

Francesco Carubbi ◽

Claudio Ferri ◽

...

Keyword(s):

Cognitive Impairment ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Demographic Shift ◽

Antihypertensive Medications ◽

Microvascular Damage ◽

Middle Way ◽

Alzheimer Type Dementia ◽

Age Related ◽

Pressure Profiles

With the demographic shift toward advanced ages, it is imperative to understand the biological mechanisms behind common, disabling age-related diseases such as cognitive impairment in its mild form to overt dementia. Hypertension, a major cardiovascular risk factor, is epidemiologically linked to vascular and Alzheimer-type dementia, with possible mechanisms being atherosclerotic macro- and microvascular damage leading to neuronal cell death, as well as proinflammatory events responsible for neurodegeneration. Nevertheless, there is currently a knowledge gap as to which population to target, what the diagnostics test, and how to manage early pathogenic events in order to prevent such a dramatic and disabling condition. While clinical trials data support the benefit of active BP control with antihypertensive medications on the risk of future cognitive impairment, hypotension appears to be related to accelerated cognitive decline in both the fit and the cognitively frail elderly. Dedicated, technologically advanced studies assessing the relation of BP with dementia are needed to clarify the pathophysiological mechanisms in the association before a tailored preventive, diagnostic, and therapeutic approach to one of the most widespread modern medical challenges becomes a reality.

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Pathogenicity and virulence of Japanese encephalitis virus: Neuroinflammation and neuronal cell damage

Virulence ◽

10.1080/21505594.2021.1899674 ◽

2021 ◽

Vol 12 (1) ◽

pp. 968-980

Author(s):

Usama Ashraf ◽

Zhen Ding ◽

Shunzhou Deng ◽

Jing Ye ◽

Shengbo Cao ◽

...

Keyword(s):

Japanese Encephalitis Virus ◽

Japanese Encephalitis ◽

Cell Damage ◽

Neuronal Cell ◽

Encephalitis Virus

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Surfactant toxicity in a case of (4-chloro-2-methylphenoxy) acetic acid herbicide intoxication

Human & Experimental Toxicology ◽

10.1177/0960327114559612 ◽

2014 ◽

Vol 34 (8) ◽

pp. 848-855 ◽

Cited By ~ 4

Author(s):

I Hwang ◽

JW Lee ◽

JS Kim ◽

HW Gil ◽

HY Song ◽

...

Keyword(s):

Acetic Acid ◽

Cell Viability ◽

Cell Damage ◽

Neuronal Cell ◽

University Hospital ◽

Cellular Damage ◽

Polypropylene Glycol ◽

Toxic Symptom ◽

Diphenyltetrazolium Bromide ◽

Low Cytotoxicity

Objective: Self-poisoning with (4-chloro-2-methylphenoxy) acetic acid (MCPA) is a common reason for presentation to hospitals, especially in some Asian countries. We encountered a case of a 76-year-old woman who experienced unconsciousness, shock and respiratory failure after ingesting 100 mL MCPA herbicide. We determined whether the surfactant in the formulation was the chemical responsible for the toxic symptom in this patient. Design: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability and lactate dehydrogenase (LDH) cytotoxicity assays were performed on human brain neuroblastoma SK-N-SH cells. The expressions of 84 genes in 9 categories that are implicated in cellular damage pathways were quantified using an RT2 Profiler™ PCR array on a human neuronal cell line challenged with polyoxyethylene tridecyl ether (PTE). Setting: Pesticide intoxication institute in university hospital. Interventions: Extracorporeal elimination with intravenous lipid emulsion. Measurements: Cell viability and gene expression. Main Results: In the MTT assay, MCPA only minimally decreased cell viability even at concentrations as high as 1 mM. Cells treated with 1-methoxy-2-propanol, dimethylamine and polypropylene glycol exhibited minimal decreases in viability, whilst the viability of cells challenged with PTE decreased dramatically; only 15.5% of cells survived after exposure to 1 µM PTE. Similarly, the results of the LDH cytotoxicity assay showed that MCPA had very low cytotoxicity, whilst cells treated with PTE showed incomparably higher LDH levels ( p < 0.0001). PTE up-regulated the expressions of genes implicated in various cell damage pathways, particularly genes involved in the inflammatory pathway. Conclusions: The surfactant PTE was likely the chemical responsible for the toxic symptom in our patient.

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The combination of Acalypha indica–Centella asiatica extracts decreases the neuronal damage in hypoxia-induced hippocampal injury animal model

Medical Journal of Indonesia ◽

10.13181/mji.v27i3.1697 ◽

2018 ◽

Vol 27 (3) ◽

pp. 137-44

Author(s):

Siti Farida ◽

Desak G.B. Krisnamurti ◽

Ninik Mudjihartini ◽

Erni H. Purwaningsih ◽

Imelda M. Sianipar ◽

...

Keyword(s):

Animal Model ◽

Neuronal Damage ◽

Cell Damage ◽

Neuronal Cell ◽

Centella Asiatica ◽

Nerve Cells ◽

Control Treatment ◽

Control Group ◽

Sprague Dawley ◽

Acalypha Indica

Background: Approximately 80–85% of strokes are ischemic and lead to alterations in neuronal cell morphology and cell death. There is a lack of studies on the effect of the combination of Acalypha indica L. (AI) and Centella asiatica L. (CA) in terms of its neurotherapy property. This study was conducted to investigate the neurotherapeutic effect of the combination of AI–CA extracts in improving rat’s hippocampal neuron injury post-hypoxia.Methods: A total of 36 Sprague-Dawley rats were categorized into six groups and placed in a hypoxia chamber for 7 consecutive days. Then, they were moved to normoxia cages and treated for 7 consecutive days as follows: control group without treatment as a negative control; treatment groups were administered citicoline 50 mg/kgBW as a positive control; three different dose combinations of AI150–CA150, AI200–CA150, and AI250–CA150 mg/kgBW, respectively. Histological analyses were performed to assess the improvement in nerve cell damage in the hippocampus.Results: Treatment with citicoline significantly decreased the damage of nerve cells (30.8%); the combination of the AI–CA extracts of AI150–CA150, AI200–CA150, and AI250–CA150 also significantly decreased the damage of nerve cells (36%, 36.4%, and 30.4%, respectively) compared to the control rats (15.4%).Conclusion: The combination of AI–CA extracts decreased the neuronal damage in the hypoxia-induced hippocampal injury animal model. The improvement effect of the combination of AI–CA extracts was not significantly different to citicoline.

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AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage

BioMed Research International ◽

10.1155/2018/3706047 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 10

Author(s):

Xiao Lin ◽

Haotuo Ye ◽

Felix Siaw-Debrah ◽

Sishi Pan ◽

Zibin He ◽

...

Keyword(s):

Cell Death ◽

Intracerebral Hemorrhage ◽

Cell Damage ◽

Neuronal Cell ◽

Neurological Function ◽

Inflammatory Factors ◽

Neuroprotective Effects ◽

Caspase 1 ◽

Cell Death Pathways ◽

Cell Death Pathway

Intracerebral hemorrhage (ICH) refers to bleeding in the brain and is associated with the release of large amount of inflammasomes, and the activation of different cell death pathways. These cell death pathways lead to removal of inactivated and damaged cells and also result in neuronal cell damage. Pyroptosis is a newly discovered cell death pathway that has gained attention in recent years. This pathway mainly depends on activation of caspase-1-mediated cascades to cause cell death. We tested a well-known selective inhibitor of caspase-1, AC-YVAD-CMK, which has previously been found to have neuroprotective effects in ICH mice model, to ascertain its effects on the activation of inflammasomes mediated pyroptosis. Our results showed that AC-YVAD-CMK could reduce caspase-1 activation and inhibit IL-1β production and maturation, but has no effect on NLRP3 expression, an upstream inflammatory complex. AC-YVAD-CMK administration also resulted in reduction in M1-type microglia polarization around the hematoma, while increasing the number of M2-type cells. Furthermore, AC-YVAD-CMK treated mice showed some recovery of neurological function after hemorrhage especially at the hyperacute and subacute stage resulting in some degree of limb movement. In conclusion, we are of the view that AC-YVAD-CMK could inhibit pyroptosis, decrease the secretion or activation of inflammatory factors, and affect the polarization of microglia resulting in improvement of neurological function after ICH.

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Effects of Gossypium herbaceam Extract Administration on the Learning and Memory Function in the Naturally Aged Rats: Neuronal Niche Improvement1

Journal of Alzheimer s Disease ◽

10.3233/jad-2012-112153 ◽

2012 ◽

Vol 31 (1) ◽

pp. 101-111 ◽

Cited By ~ 4

Author(s):

Yanyong Liu ◽

Haji Akber Aisa ◽

Chao Ji ◽

Nan Yang ◽

Haibo Zhu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Learning And Memory ◽

Memory Impairment ◽

Neuroprotective Effect ◽

Memory Function ◽

Aged Rats

Aging-associated cognitive impairment is an important health care issue since individuals with mild cognitive impairment are more likely to develop Alzheimer’s disease. In the present study, the protective effect of Gossypium herbaceam extracts (GHE) on learning and memory impairment associated with aging were examined in vivo using Morris water maze and step through task. Furthermore, the antioxidant activity and neuroprotective effect of GHE was investigated with methods of histochemistry and biochemistry. These data showed that oral administration with GHE at the doses of 35, 70, and 140 mg/kg exerted an improved effect on the learning and memory impairment in aged rats. Subsequently, GHE afforded a beneficial action on eradication of free radicals without influence on the activity of glutathione peroxidase and superoxide dismutase. GHE treatment enhanced the expression levels of nerve growth factor. Meanwhile, proliferation of neural progenitor cells was elevated in hippocampus after treatment with GHE. Taken together, neurogenic niche improvement could be involved in the mechanism underlying neuroprotection of GHE against aging-associated cognitive impairment. These findings suggested that GHE might be a potential agent as cognitive-enhancing drugs that delay or halt mild cognitive impairment progression to Alzheimer’s disease or treatment of aging-associated cognitive impairment.

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