Degenerative Changes In Brain Research Articles

Degenerative brain changes associated with tramadol use: an optical coherence tomography study

BackgroundTramadol—a synthetic opioid originally used as an analgesic—has been widely misused as an addictive drug in the middle east in the last twenty years. Brain changes associated with long-term tramadol use are understudied. This study aimed to detect the possible effects of tramadol use for at least one year on the brain. Optical coherence tomography (OCT) as a noninvasive measure can assess changes in retinal thickness which reflects degenerative changes in the brain.MethodsTwenty-five patients fulfilling the tramadol use disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria were compared to 25 matched control subjects free of substance use disorders. Other psychiatric and medical conditions that may affect OCT were excluded from both groups. Patients were assessed using Addiction Severity Index; meanwhile, both groups were evaluated using OCT.ResultsPatients with tramadol use showed a lower thickness of most OCT parameters than healthy non-tramadol controls. The retinal nerve fiber layer (RNFL) thickness was not associated with tramadol dose, duration of use, or the age of first use. There were differences between the right and left eyes in RNFL and Ganglion cell complex (GCC) thickness.ConclusionsLong-term tramadol use is associated with decreased thickness of RNFL that can be a potential marker and an early sign for degeneration detected by noninvasive techniques like OCT.

Twenty Years of Managed Epilepsy for a Stranded Male Guadalupe Fur Seal (Arctocephalus townsendi) Secondary to Suspect Domoic Acid Toxicosis

Many wild otariids (sea lions and fur seals) strand along the California coast annually with seizures following presumed exposure to harmful algal blooms (HABs). This is a long-term case study of a stranded subadult male Guadalupe fur seal (Arctocephalus townsendi) that stranded in 2001 and within days after admission began demonstrating seizure activity. The epilepsy was stabilized with antiepileptic drug (AED) therapy and advanced imaging was performed. Magnetic resonance (MR) scans showed signs of encephalopathy consistent with domoic acid (DA) toxicosis. This fur seal was deemed “non-releasable” and over the following 19 years, he received supportive veterinary care and AED treatment at a permitted facility. In the summer of 2020, the fur seal showed progressive behavioral and functional deterioration whereupon humane euthanasia was performed. Post-mortem MR and diffusion tensor images (DTI) were acquired. A volumetric comparison with historic scans showed evidence of severe progressive unilateral right hippocampal atrophy. Histopathology confirmed severe chronic right and mild left hippocampal atrophy. The progressive degenerative brain changes demonstrate how adaptive brain function can be with neuronal atrophy secondary to DA exposure. This case highlights some considerations and decision-making processes needed for the rehabilitation and placement of wild stranded otariids with acquired epilepsy secondary to DA toxicity.

Coral fossil: A potential adsorbent of natural source for cadmium removal in broilers

Cadmium (Cd) is a pollutant that poses a health risk for humans and animals. Coral fossil (CF) acts as an adsorbent, yet limited knowledge is available on impacts of CF on Cd toxicities. The work was performed to figure out the effects of CF on hematobiochemical details and specific organs in Cd exposed broilers. The experiment was carried out with 45 broilers and were divided into three groups (15 in each). Group A was served as control. The birds in group B received Cd (75 mg /kg b. w.) orally. Whereas group C was orally supplemented with Cd (75 mg /kg b. w.) and CF (1 gm/kg b. w.). The trial was lasted for 30 days. For hematobiochemical analysis, blood samples were drawn, and sera were separated. Liver, kidney and muscle were collected to assess accumulation concentration. Brain, liver and kidney samples were also collected for histopathological study. The results showed that hematological parameters (TEC, Hb, PCV, MCV, MCH, MCHC and DLC) were altered by Cd but restored with CF supplementation. Liver (AST, ALT and ALP) and kidney (total protein and creatinine) biomarkers were increased significantly in Cd treated broilers while decreased significantly after CF supplementation. CF reduced accumulation concentration of Cd in liver, kidney and muscle. Cd intoxicated broilers showed degenerative changes in brain, hyperplastic bile duct and proliferation of renal tubular epithelium with focal degeneration and necrosis; and these were improved after CF supplementation. Therefore, it can be concluded that CF is a potential adsorbent against Cd toxicities.

A Closer Look at Hearing Loss, Dementia, and Stigma

A Closer Look at Hearing Loss, Dementia, and Stigma

Effect of Phyllanthus amarus in sodium arsenite-induced tissue damage

This study aims to evaluate the effect of alcoholic extract of Phyllanthus amarus leaves on arsenic-induced histological changes in Wistar rats. Rats were divided into 4 groups: Group I: normal control; Group II: rats received sodium arsenite (40 mg/kg); Group III: rats received sodium arsenite (40 mg/kg) + P. amarus extract (100 mg/kg); Group IV: rats received sodium arsenite (40 mg/kg) + extract (200 mg/kg). All groups were treated by oral gavage with sodium arsenite for 28 days and the animals were subsequently administered (oral) with 100 and 200 mg/kg extract, once daily for two weeks. Animals were sacrificed 24 hours after the last treatment and different organs were collected for histopathological analysis. Results revealed mild to severe type of necrosis and degenerative changes in brain, kidney, and liver of arsenic fed animals. In rats administered with extract showed significant improvements, and the normal histological feature of the cells was almost restored in rats. These suggest that P. amarus can be used to treat arsenic-induced multi-organ damages.

Role of Stress-Related Dopamine Transmission in Building and Maintaining a Protective Cognitive Reserve.

This short review presents the hypothesis that stress-dependent dopamine (DA) transmission contributes to developing and maintaining the brain network supporting a cognitive reserve. Research has shown that people with a greater cognitive reserve are better able to avoid symptoms of degenerative brain changes. The paper will review evidence that: (1) successful adaptation to stressors involves development and stabilization of effective but flexible coping strategies; (2) this process requires dynamic reorganization of functional networks in the adult brain; (3) DA transmission is amongst the principal mediators of this process; (4) age- and disease-dependent cognitive impairment is associated with dysfunctional connectivity both between and within these same networks as well as with reduced DA transmission.

Hypoxia and oxidative stress in cerebral circulation insufficiency - effective ways of correction

Cerebrovascular diseases (CVDs) are one of the urgent problems of clinical neurology and the second most common cause of dementia. Vascular factors leading to the development of hypoxia, oxidative stress, mitochondrial, endothelial dysfunction and, ultimately, to the development of apoptosis with the formation of degenerative brain changes are considered among the main risk factors for the development of CVD. The most important mechanisms of the development of TFR are hypoxia and oxidative stress, which indicate the need for the use of drugs with antihypoxant and antioxidant activity. Such drugs include Mexidol (ethylmethylhydroxypyridine succinate). Mexidol directly affects the pathogenetic factors of the formation of ischemic-hypoxic brain damage, has a high clinical efficacy in the treatment of various forms of cerebral circulatory insufficiency.

CURCUMIN NANOPARTICLES VERSUS CURCUMIN IN AMELIORATION OF INFLAMMATORY AND PATHOLOGICAL CHANGES DURING THE MIGRATORY PHASE OF MURINE TRICHINELLOSIS

Trichinella spiralis can cause systemic inflammatory manifestations all over the body beforehabituating their destination in the striated muscles. Its new borne larvae (NBL) most dangerousphase go via bloodstream of different organs during migration.This study explored the anti-inflammatory, antioxidant and anti-apoptotic effects of Curcumin(Cur) and Curcumin nanoparticles (Cur-Nano) on inflammatory and pathological changes occurredin different organs in murine trichinellosis during larval migratory phase.Forty (40) male Swiss albino mice were divided into four groups of ten mice each. GI: miceinfected and treated with Cur, GII: mice infected and treated with Cur-Nano, GIII: infected nontreatedmice (positive control) and GIV: non-infected non-treated (negative control). Mice wereinfected orally with 200 T. spiralis larvae per mouse. GI & GII received treatment on 13th daypost infection (dpi) for 5 successive days. All mice were sacrificed on the 30th dpi. Effects of Cur& Cur-Nano were evaluated by counting T. spiralis encysted larvae in muscle by light microscope.Frozen sera (-20°C) were used for quantitative estimation of ALT, AST, TNFα, transforminggrowth factor-β (TGF-β) and Troponin (Trop). Specimens of lung, liver, brain and heartwere fixed in neutral buffered formalin for H&E and immunohistochemical staining.The results showed that number of encysted T. spiralis larvae in GI & GII was significantlyreduced compared to GIII. In both treated groups (GI & GII), there was a significant reduction inmean levels of AST, ALT, TNFα, TGF-β, & Trop. There was significant improvement of bileduct injury and proliferation, alveolar and pleural inflammation, and bronchial epithelial proliferation,as well as improvement of degenerative changes in brain and heart. The infected nontreatedgroup (GIII) showed significant overexpression of Cyclooxygenase-2 (COX2), caspase 3,glial fibrillary acidic protein (GFAP), arginase and granzyme b, with a significant low expressionof peroxisome proliferator-activated receptors (PPARs) as compared to treated groups.

SWS/NTE-dependent neuropathy is the model system to study neurodegeneration

Today there is many described neurodegenerative D. melanogaster mutants, which characterized by development of degenerative changes in brain. One of them are a swiss cheese (sws) gene mutants. Mutations in this gene causes apoptosis of neurons and hyperwrapping of their somas by the glial cells, reducing of life expectancy and decrease of locomotion. The sws gene is the ortholog of mammal’s neuropathy target esterase (NTE / PNPLA6). NTE is s neuronal, transmembrane protein, that possesses serinesterase activity, and can be the target for neurotoxic organophosphorus compounds activity. Mutations in PNPLA6 gene cause number hereditary neurodegenerative disorders, which nowadays are incurable. The search for therapeutic agents require use of model objects because researches on humans have both methodical and ethical limitations. During two last decades D. melanogaster has proven itself as a good model for study of neurodegenerative diseases. In this review, we described general characteristics of D. melanogaster gene sws, consequences of its mutations and provided evidences of high conservatism of gene product.
 Keywords: gene swiss cheese, neuropathy target esterase, neurodegeneration, brain, life span.

Education, intelligence, and amyotrophic lateral sclerosis: A Mendelian randomization study.

ObjectiveTo systematically investigate causal relationships between educational attainment, cognitive‐related phenotypes, and amyotrophic lateral sclerosis (ALS).MethodsSummary statistics from genome‐wide association studies for educational attainment, math ability, highest math class taken, cognitive performance, intelligence, and ALS were used. A two‐sample Mendelian randomization (MR) design was applied to explore the potential causal associations between them.ResultsGenetically predisposition to longer educational attainment and harder math class taken were associated with significantly lower statistical odds ratio of ALS. For per year increase in education completed there was a 21% lower (95% confidence interval [CI] = 27–14%) in risk for ALS. For per 1‐SD increase in the highest math class taken obtained there was a 19% lower (95% CI = 9–28%) in risk for ALS. Genetically predisposition to math ability, cognitive performance, and intelligence did not decrease the risk of ALS.InterpretationThis study provides genetic support for a causal association between higher educational attainment and a lower risk of ALS. The genes related to these phenotypes are involved in almost all aspects of neuron‐to‐neuron communication. ALS patients are occasionally accompanied by varying degrees of cognitive impairment. People with greater cognitive reserve may be better able to offset damages of degenerative brain changes associated with dementia or other brain diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, or ALS.

Environmental Complexity and Research Outcomes.

Environmental complexity is an experimental paradigm as well as a potential part of animals' everyday housing experiences. In experimental uses, researchers add complexity to stimulate brain development, delay degenerative brain changes, elicit more naturalistic behaviors, and test learning and memory. Complexity can exacerbate or mitigate behavioral problems, give animals a sense of control, and allow for expression of highly driven, species-typical behaviors that can improve animal welfare. Complex environments should be designed thoughtfully with the animal's natural behaviors in mind, reported faithfully in the literature, and evaluated carefully for unexpected effects.

Autophagic Degradation Deficit Involved in Sevoflurane-Induced Amyloid Pathology and Spatial Learning Impairment in APP/PS1 Transgenic Mice.

The adverse effects of anesthetics on elderly people, especially those with brain diseases are very concerning. Whether inhaled anesthetics have adverse effects on Alzheimer’s disease (AD), which is the most common form of dementia with brain degenerative changes, remains controversial. Autophagy, a crucial biological degradation process, is extremely important for the pathogenesis of AD. In this study, the inhaled anesthetic sevoflurane elicited many enlarged autolysosomes and impaired the overall autophagic degradation in the hippocampus of an AD mouse model, which is involved in the accumulation of amyloid-β (Aβ) and spatial learning deficits. However, rapamycin treatment counteracted all these effects. The results suggested that inhaled anesthetics may accelerate the pathological process of AD, and enlarged autolysosomes may be a new marker for prediction and diagnosis of the neurotoxicity of anesthetics in AD.

Vitamin D3 attenuates cognitive deficits and neuroinflammatory responses in ICV-STZ induced sporadic Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intracellular neurofibrillary tangles and extracellular Aβ deposition. Growing experimental evidence indicate diverse biological effects of vitamin D3 including antioxidant, neuroprotective, anti-inflammatory and cardiovascular benefits. However, the underlying neuroprotective mechanism of vitamin D3 is still largely elusive. Therefore, the present study was aimed to investigate the neuroprotective effects of vitamin D3 on ICV-STZ induced sporadic AD. Our study demonstrated that vitamin D3 pretreatment significantly improved spatial learning and memory functions and effectively mitigated ICV-STZ mediated neuronal oxidative stress, mitochondrial aberrations and improved cholinergic functions. Moreover, vitamin D3 attenuated hippocampal neuroinflammatory response and reduced neuronal death in cortex and hippocampus. Our findings indicated that prophylactic vitamin D3 supplementation ameliorated ICV-STZ mediated neurobehavioral alterations, oxidative stress and neuroinflammation thereby improving cholinergic functions and reversed degenerative changes in brain. Thus, our study further provides evidence for its therapeutic supplementation for various neurodegenerative disorders including AD.

Immunofluorescence evaluation of 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine activation in zebrafish (Daino rerio) larvae brain exposed (microinjected) to propyl gallate

Propyl gallate (PG) is a chemical compound obtained by esterification of propanol with gallic acid. Due to its antioxidative properties, it is widely used in cosmetics and pharmaceutical industries as well as to protect the oils in foods such as butter, milk-based desserts, chewing gum, mayonnaise, meat, soups, cereals, spices and seasonings from rancidity. This study has been designed to assessment 8-OHdG and 4-HNE activity, and histopathological changes in the brain tissues of zebrafish larvae, which is a lecithotrophic organism, after 96 h of PG exposure via microinjecting to yolk sac of embryo. To this end, approximately 5 nL of various concentrations of PG (1, 10, and 50 ppm) has been injected into yolk sac of fertilized embryo (final exposure concentrations are 5, 50, 250 pg/egg) with micro manipulator system. After 96 h exposure time, propyl gallate caused immunofluorescence positivity of 8-OHdG and 4-HNE in the brain tissues of zebrafish larvae. PG was not effect brain tissue histopathological in low concentrations (1 and 10 ppm) but highest concentration (50 ppm) caused degenerative changes in brain. These results suggests that PG treatment could lead oxidative DNA damage by causing an increase 8-OHdG and 4-HNE activities. This strategy will enable us to better understand the mechanisms of propyl gallate in brain tissues of zebrafish larvae.

Lifetime methamphetamine dependence is associated with cerebral microgliosis in HIV-1-infected adults.

Methamphetamine (Meth) use is common among HIV-infected persons. It remains unclear whether Meth dependence is associated with long-lasting degenerative changes in the brain parenchyma and microvasculature of HIV-infected individuals. We examined the postmortem brains of 78 HIV-infected adults, twenty of whom were diagnosed with lifetime Meth dependence (18 past and two current at the final follow-up visit). Using logistic regression models, we analyzed associations of Meth with cerebral gliosis (immunohistochemistry for ionized calcium-binding adapter molecule-1 (Iba1) and glial fibrillary acidic protein (GFAP) in frontal, temporo-parietal, and putamen-internal capsule regions), synaptodendritic loss (confocal microscopy for synaptophysin (SYP) and microtubule-associated protein-2 (MAP2) in frontal cortex), β-amyloid plaque deposition (immunohistochemistry in frontal and temporo-parietal cortex and putamen), and arteriolosclerosis (histopathology in forebrain white matter). We found that Meth was associated with marked Iba1 gliosis in the temporo-parietal region (odds ratio, 4.42 (95% confidence interval, 1.36, 14.39), p = 0.014, n = 62), which remained statistically significant after adjusting for HIV encephalitis, white matter lesions, and opportunistic diseases (n = 61); hepatitis C virus seropositivity (n = 54); and lifetime dependence on alcohol, opiates, and cannabis (n = 62). There was no significant association of Meth with GFAP gliosis, SYP or MAP2 loss, β-amyloid plaque deposition, or arteriolosclerosis. In conclusion, we found lifetime Meth dependence to be associated with focal cerebral microgliosis among HIV-infected adults, but not with other brain degenerative changes examined. Some of the changes in select brain regions might be reversible following extended Meth abstinence or, alternatively, might have not been induced by Meth initially.

CJD and Scrapie Require Agent-Associated Nucleic Acids for Infection.

Unlike Alzheimer's and most other neurodegenerative diseases, Transmissible Spongiform Encephalopathies (TSEs) are all caused by actively replicating infectious particles of viral size and density. Different strain-specific TSE agents cause CJD, kuru, scrapie and BSE, and all behave as latent viruses that evade adaptive immune responses and can persist for years in lymphoreticular tissues. A foreign viral structure with a nucleic acid genome best explains these TSE strains and their endemic and epidemic spread in susceptible species. Nevertheless, it is widely believed that host prion protein (PrP), without any genetic material, encodes all these strains. We developed rapid infectivity assays that allowed us to reproducibly isolate infectious particles where >85% of the starting titer separated from the majority of host components, including PrP. Remarkably, digestion of all forms of PrP did not reduce brain particle titers. To ask if TSE agents, as other viruses, require nucleic acids, we exposed high titer FU-CJD and 22L scrapie particles to potent nucleases. Both agent-strains were propagated in GT1 neuronal cells to avoid interference by complex degenerative brain changes that can impede nuclease digestions. After exposure to nucleases that are active in sarkosyl, infectivity of both agents was reproducibly reduced by ≥99%. No gold-stained host proteins or any form of PrP were visibly altered by these nucleases. In contrast, co-purifying protected mitochondrial DNA and circular SPHINX DNAs were destroyed. These findings demonstrate that TSE agents require protected genetic material to infect their hosts, and should reopen investigation of essential agent nucleic acids. J. Cell. Biochem. 117: 1947-1958, 2016. © 2016 Wiley Periodicals, Inc.

Studying Vascular Angiogenesis and Senescence in Zebrafish Embryos.

The zebrafish is an excellent animal model to study the formation of the vertebrate vascular network. The small size, the optical translucency, and the ability to model endothelial-specific fluorescent transgenic lines in the zebrafish embryo had facilitate, in the past 10 years, the direct visualization of vessels formation and remodeling. Furthermore, zebrafish is an excellent disease model such as for cancer and neurodegenerative diseases. Cerebral amyloid angiopathy (CAA) is a human neurovascular degenerative disease, caused by Amyloid β (Aβ) peptides deposition around brain microvessels, and characterized by vascular brain degenerative changes. By using the zebrafish model, we investigated the effect of Aβ peptides treatment in vessel formation during embryogenesis. We showed that the defects in the vascular remodeling and senescence can be detected, respectively, via staining for alkaline phosphatase activity and β-galactosidase or cyclin-dependent kinase inhibitor p21 expression. We demonstrated that treating zebrafish embryos with these oxidative peptides reduces angiogenesis and promotes premature vascular senescence. In this chapter, we will describe the methods to reveal both angiogenesis and senescence defects upon Aβ peptides treatment of the zebrafish embryos.

Association between degenerative changes in brain and cognitive functions in Alzheimer’s disease

Association between degenerative changes in brain and cognitive functions in Alzheimer’s disease

Presence of brain pathology in deceased subjects with and without chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) have extrapulmonary co-morbidities, such as cardiovascular disease, musculoskeletal wasting and neuropsychological conditions. To date, it remains unknown whether and to what extent COPD is associated with a higher prevalence of brain pathology. Therefore, the aim of this retrospective study was to compare the prevalence of neuropathological brain changes between deceased donors with and without COPD. Brain autopsy reports of age-matched donors with (n = 89) and without COPD (n = 89) from the Netherlands Brain Bank were assessed for demographics, cause of death, co-morbidities and brain pathology. The prevalence of degenerative brain changes was comparable for donors with and without COPD (50.6% vs. 61.8%, p > 0.05). Neoplastic brain changes were reported in a minority of the donors (5.6% vs. 10.1%, p > 0.05). After correction for cerebrovascular accident or cardiac cause of death and Charlson co-morbidity index score, the prevalence of vascular brain changes was higher among control versus COPD donors (27.0% vs. 11.2%, adjusted p = 0.013, odds ratio = 2.98). Brain autopsy reports of donors with and without COPD did not reveal differences in the presence of degenerative or neoplastic brain changes. Vascular brain changes were described more often in controls. Prospective studies including spirometry and structural and functional brain imaging should corroborate our findings.

Mild Cognitive Impairment is Associated With White Matter Integrity Changes in Late-Myelinating Regions Within the Corpus Callosum.

Degenerative brain changes in Alzheimer's disease may occur in reverse order of normal brain development based on the retrogenesis model. This study tested whether evidence of reverse myelination was observed in mild cognitive impairment (MCI) using a data-driven analytic approach based on life span developmental data. Whole-brain high-resolution diffusion tensor imaging scans were obtained for 31 patients with MCI and 79 demographically matched healthy older adults. Comparisons across corpus callosum (CC) regions of interest (ROIs) showed decreased fractional anisotropy (FA) in the body but not in the genu or splenium; early-, middle-, and late-myelinating ROIs restricted to the CC revealed decreased FA in late- but not early- or middle-myelinating ROIs. Voxelwise group differences revealed areas of lower FA in MCI, but whole-brain differences were equally distributed across early-, middle-, and late-myelinating regions. Overall, results within the CC support the retrogenesis model, although caution is needed when generalizing these results beyond the CC.