Neurodegenerative Changes Research Articles

Obesity aggravates neuroinflammatory and neurodegenerative effects of bisphenol A in female rats

Bisphenol A (BPA), a common plasticizer, is categorized as a neurotoxic compound. Its impact on individuals exhibits sex-linked variations. Several biological and environmental factors impact the degree of toxicity. Moreover, nutritional factors have profound influence on toxicity outcome. BPA has been demonstrated to be an obesogen. However, research on the potential role of obesity as a confounding factor in BPA toxicity is lacking. We studied the neurodegenerative effects in high-fat diet (HFD)-induced obese female rats after exposure to BPA (10 mg/L via drinking water for 90 days). Four groups were taken in this study – Control, HFD, HFD + BPA and BPA. Cognitive function was evaluated through novel object recognition (NOR) test. Inflammatory changes in brain, and changes in hormonal level, lipid profile, glucose tolerance, oxidative stress, and antioxidants were also determined. HFD + BPA group rats showed a significant decline in memory function in NOR test. The cerebral cortex (CC) of the brain showed increased neurodegenerative changes as measured by microtubule-associated protein-2 (MAP-2) accompanied by histopathological confirmation. The increased level of neuroinflammation was demonstrated by microglial activation (Iba-1) and protein expression of nuclear factor– kappa B (NF-КB) in the brain. Obesity also caused significant (p < 0.05) increase in lipid peroxidation accompanied by reduced activities of antioxidant enzymes (glutathione S-transferase, catalase and glutathione peroxidase) and decrease in reduced-glutathione (p < 0.05) when compared to non-obese rats with BPA treatment. Overall, study revealed that obesity serves as a risk factor in the toxicity of BPA which may exacerbate the progression of neurological diseases.

Evaluation of Visual Cortex Activity Using Functional Near-Infrared Spectroscopy in Primary Open Angle and Primary Angle Closure Glaucoma: A Pilot Study.

Functional near-infrared spectroscopy (fNIRS) was used to assess visual cortical activity in patients with primary open angle (POAG) and primary angle closure (PACG) glaucomas. There was decreased activity in the visual cortex of glaucoma patients correlating with the severity of glaucoma. To evaluate visual cortex activity using fNIRS in POAG and PACG compared with healthy controls. A total of 30 POAGs, 31 PACGs, and 30 healthy aged-matched controls from a single centre were recruited in this cross-sectional observational pilot study with purposive sampling. The POAG and PACG groups were age-matched but were not matched for disease severity at recruitment. All participants underwent fNIRS testing using a multichannel continuous-wave near-infrared system NIRSport 8×7 device (NIRx Medizintechnik GmbH). The visual cortex activity was evaluated in terms of the maximum amplitude of change in oxyhemoglobin (OxyHb) concentration over 10 seconds, and a comparison was done among 3 groups. Both POAG and PACG groups were combined (termed as glaucoma group) to assess the relationship of visual cortical activity with disease severity (by visual field defect (mean deviation) and retinal nerve fibre layer thickness). All participants showed the characteristic response of increased OxyHb and decreased deoxyhemoglobin during stimulus presentation. The maximum amplitude of change in OxyHb concentration over 10 seconds was significantly lower in both POAG and PACG groups compared with control in the right and left middle occipital gyri ( P < 0.05). There was no significant difference between PACG and POAG. Importantly, there was a negative correlation between the visual cortex activity with the visual field defects (mean deviation; P < 0.05) and a positive correlation with retinal nerve fibre layer thickness in the glaucoma group ( P < 0.05). In patients with glaucoma, a reduction in visual cortical activity was observed, which may be indicative of neuronal degeneration occurring in the occipital cortex. Disease severity in glaucoma appears to be closely correlated with visual cortex activity. fNIRS can serve as a useful neuroimaging modality for assessing the hemodynamic and neurodegenerative changes in glaucoma.

Observation on the changes of visual field and optic nerve fiber layer thickness in patients with early diabetic retinopathy

BackgroundDiabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) and is a leading cause of vision loss. Early detection of DR-related neurodegenerative changes is crucial for effective management and prevention of vision loss in diabetic patients. MethodsIn this study, we employed spectral-domain polarization-sensitive optical coherence tomography (SD PS-OCT) to assess retinal nerve fiber layer (RNFL) changes in 120 eyes from 60 types 1 DM patients without clinical DR and 60 age-matched healthy controls. Visual field testing was performed to evaluate mean sensitivity (MS) and mean defect (MD) as indicators of visual function. ResultsSD PS-OCT measurements revealed significant reductions in RNFL birefringence, retardation, and thickness in type 1 DM patients compared to healthy controls. Visual field testing showed decreased MS and increased MD in DM patients, indicating functional impairment correlated with RNFL alterations. ConclusionOur findings demonstrate early neurodegenerative changes in the RNFL of type 1 DM patients without clinical DR, highlighting the potential of SD PS-OCT as a sensitive tool for early detection of subclinical DR-related neurodegeneration. These results underscore the importance of regular ophthalmic screenings in diabetic patients to enable timely intervention and prevent vision-threatening complications.

The potential neuroprotective of luteolin against acetamiprid-induced neurotoxicity in the rat cerebral cortex.

Acetamiprid is a class of neuroactive insecticides widely used to control insect pests. The current study aimed to investigate the potential neuroprotective effects of luteolin against acetamiprid-induced neurotoxicity in the rat cerebral cortex. Four equal groups of adult male rats (10 in each): control, acetamiprid (40 mg/kg for 28 days), luteolin (50 mg/kg for 28 days), and acetamiprid+luteolin cotreatment were used. Acetamiprid was shown to alter the oxidative state by increasing oxidant levels [nitric oxide (NO) and malondialdehyde (MDA)] and decreasing antioxidants [glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase-(CAT)], with increased activity of nuclear factor erythroid 2-related factor 2-(Nrf2). Likewise, acetamiprid increases the inflammatory response, as evidenced by increased interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nuclear factor kappa B-(NF-κB). In contrast, the treatment with luteolin brought these markers back to levels close to normal, showing that it protects neurocytes from oxidative damage and the neuroinflammation effects of acetamiprid-induced inflammation. Luteolin also demonstrated a neuroprotective role via the modulation of acetylcholinesterase (AChE) activity in the cerebral cortex tissue. Histopathology showed severe neurodegenerative changes, and apoptotic cells were seen in the acetamiprid-induced cerebral cortex layer, which was evident by increased protein expression levels of Bax and caspase-3 and decreased Bcl-2 levels. Histochemistry confirmed the neuronal degeneration, as proven by the change in neurocyte colour from brown to black when stained with a silver stain. Luteolin may have a neuroprotective effect against biochemical and histopathological changes induced by acetamiprid in the rat cerebral cortex.

Resveratrol protects against diabetic retinal ganglion cell damage by activating the Nrf2 signaling pathway

ObjectiveOxidative stress-induced retinal neurodegenerative changes are among the pathological alterations observed in diabetic retinopathy. Resveratrol (RSV), a polyphenolic compound with diverse pharmacological effects, has shown preventive qualities in several neurodegenerative illnesses, including anti-inflammatory, anti-aging, and antioxidant benefits. However, its therapeutic efficacy in diabetic retinal neurodegeneration has not yet been thoroughly elucidated. Our study aimed to explore the protective mechanisms and therapeutic benefits of RSV on diabetic retinal neurodegeneration alterations. Materials and methodsUsing streptozotocin, we created a diabetic mouse model and conducted visual electrophysiological examinations on mice from the normal group, diabetic group, and diabetic group treated with RSV. Retinas were harvested for histological staining. Additionally, primary retinal ganglion cells cultured in high glucose conditions were used to assess malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels upon siRNA-mediated nuclear factor erythroid 2-related factor 2 (Nrf2) interference. Protein levels of Nrf-2, heme oxygenase-1 (HO-1), and transcriptional levels of them were also measured. ResultsWe demonstrated that RSV significantly improved the retinal morphology and function in the diabetic retinopathy model mice. The treated mice exhibited notable improvements in visual electrophysiology, with a significant reduction in retinal ganglion cell apoptosis. Following RSV treatment, the high glucose-cultured ganglion cells demonstrated a considerable rise in SOD levels and a substantial drop in MOD. Moreover, the protein expression of solute carrier family 7 member 11 (SLC7A11) and Nrf2 significantly increased. RT-PCR and Western blot results indicated a significant attenuation of RSV's therapeutic effects upon Nrf2 inhibition. ConclusionOur findings suggest that RSV may reduce oxidative stress levels in the retina and inhibit retinal ganglion cell apoptosis via reducing the Nrf2/HO-1 pathway, which lessens the harm that excessive glucose causes to the retina.

Histological and Memory Alterations in an Innovative Alzheimer's Disease Animal Model by Vanadium Pentoxide Inhalation.

Previous work from our group has shown that chronic exposure to Vanadium pentoxide (V2O5) causes cytoskeletal alterations suggesting that V2O5 can interact with cytoskeletal proteins through polymerization and tyrosine phosphatases inhibition, causing Alzheimer's disease (AD)-like hippocampal cell death. This work aims to characterize an innovative AD experimental model through chronic V2O5 inhalation, analyzing the spatial memory alterations and the presence of neurofibrillary tangles (NFTs), amyloid-β (Aβ) senile plaques, cerebral amyloid angiopathy, and dendritic spine loss in AD-related brain structures. 20 male Wistar rats were divided into control (deionized water) and experimental (0.02 M V2O5 1 h, 3/week for 6 months) groups (n = 10). The T-maze test was used to assess spatial memory once a month. After 6 months, histological alterations of the frontal and entorhinal cortices, CA1, subiculum, and amygdala were analyzed by performing Congo red, Bielschowsky, and Golgi impregnation. Cognitive results in the T-maze showed memory impairment from the third month of V2O5 inhalation. We also noted NFTs, Aβ plaque accumulation in the vascular endothelium and pyramidal neurons, dendritic spine, and neuronal loss in all the analyzed structures, CA1 being the most affected. This model characterizes neurodegenerative changes specific to AD. Our model is compatible with Braak AD stage IV, which represents a moment where it is feasible to propose therapies that have a positive impact on stopping neuronal damage.

Subacute Use of Aqueous Extract of Water Melon (Citrullus lanatus) Seeds Mitigates against Pyramidal Neuronal Toxicity of Lead Acetate in Adult Wistar Rats

Introduction: Lead exposure remains a significant public health burden across the globe, impacting millions of individuals and posing a major threat to nervous system development and function As a reported bio-toxic environmental and industrial pollutant, Lead (Pb) do accumulates in almost all body tissues to cause health complications with the cerebellar region of the central nervous system reported to be more susceptible to cellular distortions. As a flowering plant species of the Cucurbitaceae family, watermelon (Citrullus lanatus) is associated with numerous medicinal properties. Aim: This study aim to investigate the possible neuroprotective potential of aqueous extract of citrulus lanatus seed on lead acetates-induced neurotoxicity in the Cerebral cortex of adult Wistar rats. Place of Study: Department of Anatomy, Faculty of Basic Medical Sciences Olabisi Onabanjo University, Ogun State, Nigeria. Methods: Twenty (20) healthy adult female wistar rats weighing 150±50g were randomly assigned into 4 groups (n=5). The Control group received 2mls/kg of distilled water, Treatment group (T1) was administered 7.5 mg/kg of lead acetate, Treatment group (T2) was administered 200 mg/kg of aqueous extract of citrullus lanatus and Treatment group (T3) was administered 7.5 mg/kg of lead acetate and 200 mg/kg of aqueous extract of citrullus lanatus concomitantly orally for fourteen (14) days. H&amp;E and Cresyl violet histological stains and Biochemical assays for SOD, CAT activities and MDA concentration was determined. Data obtained from the study were analyzed using one-way ANOVA and subjected to Turkeys post hoc test from the multiple comparison. Results: Revealed no statistically significant differences (p&gt;0.05) in body weight and brain weight changes across groups relatives to the control group while SOD and Catalase activities were increased significantly in the Treatment groups compared to control group. Histological findings in control group and T2 showed normal histoarchitectural appearance of cerebral cortex Pyramidal neurons while the lead exposed group (T1) revealed features of neurodegenerative changes evident by nuclear shrinkage with pyknosis and karryorrhexis. while T3 revealed near normal presentations. Conclusion: In summary, Citrullus lanatus mitigates against pyramidal neuronal cells distortions following lead acetate induced toxicity in Wistar Rats and also further affirms its antioxidative potential.

Amelioration of cisplatin-induced neurodegenerative changes in rats and restoration of mitochondrial biogenesis by 6-bromoindirubin-3′-oxime: The implication of the GSK-3β/PGC1-α axis

BackgroundThe cognitive deficits observed after treatment with chemotherapeutic drugs are obvious clinical problems. For treating chemotherapy-induced cognitive deficits (CICD), the treatment modalities must target its underlying mechanisms. Specifically, cisplatin may activate glycogen synthase kinase-3β (GSK-3β), thereby enhancing neuronal apoptosis. 6-bromoindirubin-3′-oxime (6BIO) was not investigated previously in a model of CICD. Therefore, this investigation aimed to address the impacts of GSK3 inhibition on regulating cell signaling, which contributes to neurodegeneration and cognitive impairment. MethodsThirty adult male Wistar rats were randomly allocated into control groups, while two experimental groups were exposed to repeated cisplatin injections (2 mg/kg intraperitoneally (ip), twice weekly, nine injections), termed chemobrain groups. The rats in the two experimental groups were equally divided into the chemobrain group (untreated) and the chemobrain-6BIO group (treated with 6BIO at a dose of 8.5 μg/kg ip every two days, started after the last dose of cisplatin and continued for two weeks). ResultsRepeated exposure to cisplatin led to a marked decline in cognitive functions. GSK3 inhibition exerted neuroprotection by decreasing the expression of p-tau and amyloid β, thereby improving cognition. 6BIO, the GSK-3β inhibitor, restored mitochondrial biogenesis by augmenting the protein levels of PGC1-α and increasing the number of mitochondria in the cerebral cortex and hippocampus. Conclusion6BIO provided neuroprotection and exhibited anti-apoptotic and anti-oxidative effects in a rat model of chemobrain.

Compartmental neuronal degeneration in the ventral striatum induced by status epilepticus in young rats' brain in comparison with adults.

According to experimental and clinical studies, status epilepticus (SE) causes neurodegenerative morphological changes not only in the hippocampus and other limbic structures, it also affects the thalamus and the neocortex. In addition, several studies reported atrophy, metabolic changes, and neuronal degeneration in the dorsal striatum. The literature lacks studies investigating potential neuronal damage in the ventral component of the striatopallidal complex (ventral striatum [VS] and ventral pallidum) in SE experimentations. To better understand the development of neuronal damage in the striatopallidal complex associated with SE, the detected neuronal degeneration in the compartments of the VS, namely, the nucleus accumbens (NAc) and the olfactory tubercle (OT), was analyzed. The experiments were performed on Wistar rats at age of 25-day-old pups and 3-month-old adult animals. Lithium-pilocarpine model of SE was used. Lithium chloride (3mmol/kg, ip) was injected 24 h before administering pilocarpine (40 mg/kg, ip). This presented study demonstrates the variability of post SE neuronal damage in 25-day-old pups in comparison with 3-month-old adult rats. The NAc exhibited small to moderate number of Fluoro-Jade B (FJB)-positive neurons detected 4 and 8h post SE intervals. The number of degenerated neurons in the shell subdivision of the NAc significantly increased at survival interval of 12 h after the SE. FJB-positive neurons were evidently more prominent occupying the whole anteroposterior and mediolateral extent of the nucleus at longer survival intervals of 24 and 48 h after the SE. This was also the case in the bordering vicinity between the shell and the core compartments but with clusters of degenerating cells. The severity of damage of the shell subdivision of the NAc reached its peak at an interval of 24 h post SE. Isolated FJB-positive neurons were detected in the ventral peripheral part of the core compartment. Degenerated neurons persisted in the shell subdivision of the NAc 1 week after SE. However, the quantity of cell damage had significantly reduced in comparison with the aforementioned shorter intervals. The third layer of the OT exhibited more degenerated neurons than the second layer. The FJB-positive cells in the young animals were higher than in the adult animals. The morphology of those cells was identical in the two age groups except in the OT.

Neuropathologic changes at age 90+ related to sleep duration 19 to 40 years earlier: The 90+ Study.

We investigated the association between sleep duration and neuropathologic changes 19 to 40 years later in oldest-old (age 90+) participants of The 90+ Study. Participants self-reported sleep duration and underwent neuropathologic evaluation. We categorized sleep duration as<7, 7 to 8=reference,>8hours and dichotomized neuropathologic changes as present/absent. We estimated odds ratio (OR) and 95% confidence intervals (CI) using logistic regression. In 264 participants, mean age at sleep self-report was 69 years, mean age at autopsy was 98 years, and mean interval between sleep self-report and autopsy was 29 years (range: 19-40). Those reporting>8hours of sleep had lower likelihood of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) inclusions (OR=0.18; CI=0.04-0.82) and amyloid beta deposits (OR=0.34; 95% CI=0.12-0.94). Long self-reported sleep is associated with lower odds of neurodegenerative neuropathologic changes 19 to 40 years later in the oldest-old, suggesting a potential role of sleep in accumulation of dementia-related neuropathologies. Association of self-reported sleep with non-Alzheimer's disease neuropathologic changes has not been explored. Whether sleep duration is related to dementia neuropathologic changes decades later is unclear. Long self-reported sleep is associated with lower odds of Alzheimer's disease neuropathologic change 19 to 40 years later in the oldest-old. Long self-reported sleep is associated with lower odds of limbic-predominant age-related TDP-43 encephalopathy neuropathologic change 19 to 40 years later in the oldest-old.

3,5-Dimethyladamantan-1-amine Restores Short-term Synaptic Plasticity by Changing Function of Excitatory Amino Acid Transporters in Mouse Model of Spinocerebellar Ataxia Type 1

Introduction. Memantine is an agent that used for treatment of Alzheimer's type dementia. Memantine considerably reduces the effects of neurodegeneration, may potentially slow down the neurodegenerative changes in the cerebellum and may act as treatment of choice for spinocerebellar ataxia type 1 (SCA 1).&#x0D; Our objective was to study molecular mechanisms of the short-term synaptic plasticity improvement associated with long-term memantine use in SCA 1 transgenic mice.&#x0D; Materials and methods. The experiments were performed on 12-week-old CD1 mice. We created a mouse model of cerebellar astrogliosis after expression of mutant ataxin-1 (ATXN1[Q85]) in the Bergmann glia (BG). To model the astrocyte-mediated neurodegeneration in the cerebellum, the mice were injected with LVV GFAP-Flag-ATXN1[Q85] lentiviral vector (LVV) constructs intracortically. Some of the mice received 0.35 mg/kg memantine dissolved in drink water once daily for 9 weeks. The control animals were administered LVV GFAP-ATXN1[Q2]-Flag. Changes of the excitatory postsynaptic currents amplitudes from Purkinje cells (PC) were recorded by patch clamp. Expression of anti-EAAT1 in the cerebellar cortex was assessed using immunohistochemistry.&#x0D; Results. The reactive glia of the cerebellar cortex in SCA1 mice is characterized by a decrease in the immunoreactivity of anti-EAAT1, while chronic memantine use restores this capacity. The decay time of the excitatory postsynaptic current amplitude in the parallel fiber-Purkinje cell (PF-PC) synapses of the SCA1 mice is considerably longer, which indicates the slowing of glutamate reuptake and EAAT1 dysfunction. The prolonged presence of increased neurotransmitter levels in the synaptic cleft facilitates activation of the mGluR1 signaling and restoration of mGluR1-dependent synaptic plasticity in Purkinje cells of the SCA1 mice.&#x0D; Conclusions. The slowing of neurotransmitter reuptake associated with long-term memantine treatment improves mGluR1-dependent short-term synaptic plasticity of the Purkinje cells in the SCA1 mice. Restoration of synaptic plasticity in these animals may underlie partial reduction of ataxic syndrome.

Loss of GDE2 leads to complex behavioral changes including memory impairment

BackgroundAlzheimer’s disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there are currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, and little is known about the underlying mechanisms that contribute to sporadic disease. Accordingly, it is important to expand investigations into possible pathways that may contribute to disease pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a membrane-bound enzyme that acts at the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers distinct proteins to the membrane. GDE2 abnormally accumulates in intracellular compartments in the brain of patients with AD, ALS, and ALS/FTD, indicative of GDE2 dysfunction. Mice lacking GDE2 (Gde2KO) show neurodegenerative changes such as neuronal loss, reduced synaptic proteins and synapse loss, and increased Aβ deposition, raising the possibility that GDE2 disruption in disease might contribute to disease pathophysiology. However, the effect of GDE2 loss on behavioral function and learning/memory has not been characterized.ResultsHere, we show that GDE2 is expressed throughout the adult mouse brain in areas including the cortex, hippocampus, habenula, thalamus, and amygdala. Gde2KO and WT mice were tested in a set of behavioral tasks between 7 and 16 months of age. Compared to WT, Gde2KO mice display moderate hyperactivity that becomes more pronounced with age across a variety of behavioral tests assessing novelty-induced exploratory activity. Additionally, Gde2KO mice show reduced startle response, with females showing additional defects in prepulse inhibition. No changes in anxiety-associated behaviors were found, but Gde2KOs show reduced sociability. Notably, aged Gde2KO mice demonstrate impaired short/long-term spatial memory and cued fear memory/secondary contextual fear acquisition.ConclusionsTaken together, these observations suggest that loss of GDE2 leads to behavioral deficits, some of which are seen in neurodegenerative disease models, implying that loss of GDE2 may be an important contributor to phenotypes associated with neurodegeneration.

Glycemic Variability and the Thickness of Retinal Layers in Cystic Fibrosis Patients with and without Cystic Fibrosis Related Diabetes

Purpose Patients with cystic fibrosis (CF) are at risk to develop CF related diabetes (CFRD) and subsequently even diabetic neuro- and/or vasculopathy. We sought to determine if there are typical signs of diabetes-related retinal alterations present in CF patients with preserved and impaired glycemic control. Methods During routine annual examination CF patients were offered an additional 7-day period of real time continuous glucose monitoring (rtCGM) and an ophthalmological examination including retinal optical coherence tomography (OCT). Patients were categorized according to the glycemic control, i.e. the results of an oral glucose tolerance test (OGTT) and rtCGM were taken into consideration. OCT data was analyzed by our previously published visual analysis software generating dedicated and spatially resolved deviation maps for visualization and quantification of differences in total retinal thickness and thickness of retinal nerve fiber layer (RNFL) as well as ganglion cell layer (GCL) in comparison to age-matched healthy controls and patients with either type 1 or type 2 diabetes mellitus. Results Results of the rtCGM and/or OGTT enabled discrimination between patients with normal glycemic control (CFNG; n = 6), with abnormal glycemic control (CFAG; n = 6) and overt CFRD (n = 4). OCT data indicates gradually increasing retinal thinning in all 3 groups, depending on the degree of glucose metabolism disorder compared to healthy controls. At the foveal region total retinal thickness and GCL thickness were significantly thinner in CFRD patients compared to CFNG patients (total retinal thickness: 260.4 µm (239.3–270.8) vs. 275.4 µm (254.3–289.5); GCL: 11.82 µm (11.16–15.25) vs. 17.30 µm (13.95–19.82); each p < 0.05). Conclusion Although we investigated a rather small number of patients, we obtained evidence that intraretinal neurodegenerative changes occur in each of our subgroups (CFNG, CFAG, CFRD). Beyond this, our results favor the detrimental role of additional diabetes, as the deviations from healthy controls were most pronounced in the CFRD group and are similar to those seen in patients suffering from type 1 or type 2 diabetes.

443 Myeloid Immunometabolic Reprogramming Mitigates Chronic Neurodegeneration After Experimental Traumatic Brain Injury

INTRODUCTION: Traumatic brain injury (TBI) induces immediate mechanical injury, including diffuse axonal shearing and myelin degradation. Epidemiological studies suggest a single, severe TBI initiates progressive neurodegeneration, including extensive white matter injury and culminating in long-term cognitive decline. While underlying mechanisms remain undefined, the degree of chronic inflammation correlates with delayed white matter tract damage after TBI. METHODS: Immune cell infiltration and activation was measured using preparative and analytical flow cytometry after controlled cortical impact, a pre-clinical model of focal penetrating injury, in adult mice. To assess T cell priming, APCs pulsed with myelin or isolated after experimental TBI were co-cultured with naÏve splenic T cells. Progressive neurodegeneration was assessed by histology and magnetic resonance imaging at eight weeks post-injury. RESULTS: Peripheral macrophages predominated as APCs within the CNS parenchyma after severe TBI. Myelin-pulsed APCs or APCs isolated after experimental TBI efficiently primed naÏve T cells ex vivo, generating myelin-reactive Th1/Th17 cells. Activity of the master metabolic regulator AMPK, previously shown to promote counter-inflammatory immune polarization, was decreased in myeloid cells after injury. Treatment with metformin, an AMPK activator, restored myeloid AMPK activity and attenuated neurodegenerative changes at eight weeks post-TBI. CONCLUSIONS: TBI-induced immunometabolic dysregulation allows generation of auto-reactive T cells that may contribute to chronic inflammation and progressive neurodegeneration. Metabolic reprogramming of myeloid cells via metformin restores AMPK activity and reduces progressive white matter loss after TBI, representing a potential therapeutic intervention to mitigate long-term consequences of TBI.

A Study of Neurodegenerative Changes in the CA1 Region of the Dorsal Hippocampus in Adult Rats with Prenatal Hyperhomocysteinemia

A Study of Neurodegenerative Changes in the CA1 Region of the Dorsal Hippocampus in Adult Rats with Prenatal Hyperhomocysteinemia

Cerebral-cognitive reserve: concept and functions of the cerebral-cognitive reserve

IntroductionThe modern understanding of AD allows us to consider it through the constructs of “vulnerability” and “stability” of the brain as a dynamic system of dialectical interaction between the pathogenic process and the protective process that prevents neurodegeneration. The concept of cognitive reserve (CR) is based on observations of discrepancy between the degree of brain pathology and the severity of clinical manifestations. The concept of “reserve” was proposed to describe the resistance of the brain to a developing damage caused by a pathological process. Stern (2002) considered CR as a protective factor that modifies the impact of brain pathology on cognitive function. The researchers have defined CR as an ability to optimize cognitive function through differential involvement of structures or neural networks of the brain into brain activity.ObjectivesA systematic review of scientific studies has been conductedMethodsThe review includes an analysis of full-text literature sources.ResultsSeveral possible directions of CR influence on cognitive functions have been described:1)CR may reduce the risk of MCI or dementia through mechanisms, which do not depend on the level of neurodegenerative pathological changes in the brain.2)CR can interact with the markers of brain pathology or healthaffectingthe future cognitive decline or risk of progression. It has been found that smaller volumes or thickness in some AD vulnerable areas of the brain represent a stronger risk factor for cognitive impairment in people with low CR than in people with higher CR. CR protective effects on clinical outcomes reduce as the number of damaged neurons increases.3)The protective effect of CR increasesduring late AD onset and at a low rate of the damaged substrate accumulation.4)CR changes the relationship between genetic factors and aging withclinical and cognitive outcomes. The relationship between age and AD pathology level or age-related structural changes in the brain may weaken in people with higher CR ConclusionsThe concept of cerebral-cognitive reserve actualizes the problem of the search for compensatory mechanisms of cognitive deficit in AD, the assessmentof the structure of the reserve, the development and implementationof programs to maintain the reserve, the preventionof its depletion, starting from the preclinical stage of the disease, which can prevent the transformation of preclinical manifestations of AD into cognitive disordersDisclosure of InterestNone Declared

Central effects of peripherally administrated immune cells modulated by a psychoactive substance in aggression

IntroductionIt is known that the formation of aggressive behavior is accompanied by neurodegenerative and neuroinflammatory changes. Immune cells have a regulatory effect on the central nervous system functions, including regulation of behavior.ObjectivesWe first demonstrated that ex vivo chlorpromazine - modulated immune cells have a positive aggressive behavior editing effect. The aim of the study was to investigate the influence of the indicated cells on some central mechanisms underlying the development of aggressive reactions.Methods(CBAxC57Bl/6) F1 aggressive male mice, developed in conditions of chronic social stress, were undergoing the transplantation of syngeneic spleen lymphocytes with ex vivo chlorpromazine-modulated functional activity. In recipients the immunohistochemical analysis was performed assessing the expression of the microglial marker Iba1. The levels of brain-derived neurotrophic factor (Bdnf ) and cytokines was assessed by ELISA. For histological examination Nissl staining was applied.ResultsAggressive behavior editing after the chlorpromazine-modulated immune cells transplantation registered against the background of some structural and functional changes in the brain. It was found an increase in the density of pyramidal neurons in CA1 and CA3 hippocampal regions and augmented level of Bdnf. The decreased expression of microglial activation marker Iba1, accompanied with decreased levels of pro-inflammatory cytokines (IL-1β, IL-2, IL-6, INF-γ) and increased anti-inflammatory (IL-4) cytokine was found. Visualization of functionally active lymphocytes pre-treated with chlorpromazine in the brain parenchyma of aggressive recipients suggests a direct effect of injected lymphocytes on CNS.ConclusionsThe effect of chlorpromazine - modulated immune cells that edits aggressive behavior is realized by stimulating neurogenesis, neuroplasticity and reducing neuroinflammation.Disclosure of InterestNone Declared

Neuropathological changes in the TASTPM mouse model of Alzheimer’s disease and their relation to hyperexcitability and cortical spreading depolarization

Although Alzheimer’s disease (AD) is characterized by distinct pathological changes, their precise impact on cortical functions are not well understood. Here we used TASTPM mice as an AD model and asked whether the development of neurodegenerative changes has an impact on the extracellular space (ECS) and neuronal excitability, in particular cortical spreading depolarization (CSD) which requires intact neuron and glial functions. We studied wildtype (WT) and TASTPM mice (3, 6, and 12 months old). TASTPM mice showed progressive proliferation of neocortical Amyloid-beta (Aβ) plaques between 3 and 12 months (more deposits in females than in males) and Aβ accumulation in cortical vessels. As plaques proliferated, neuroinflammatory microglial reaction (CD68, CD39 and Galectin-3) and astrogliosis (GFAP) developed progressively. The cortical ECS volume shrank significantly to about half the size of the WT. CSD in both WT and TASTPM mice showed considerable heterogeneity but did not correlate with the histological changes. However, CSDs were easier to elicit in TASTPM than in WT mice at 3 months, and also compared to older TASTPM mice. Moreover, TASTPM mice showed more hyperexcitability manifested as clonic-tonic behavior after sodium thiopental anesthesia. Thus, AD pathology was associated with abnormal hyperexcitability but did not homogenously alter CSD susceptibility.

Walker In Conjunction With Haptic Feedback System For Muscle Relief

Walkers are important devices that aid the rehabilitation process. The use of a walker is recommended for gait changes and imbalance due to various factors, such as surgery of the lower limbs or neurodegenerative changes, especially in the early recovery period. In this project we design a solution for the patient using walkers, this device helps them to maintain the proper balance. The system's foundation lies in a network of strategically placed sensors, including gyroscopes, accelerometers, and pressure sensors, meticulously capturing data on the user's body posture and gait patterns. This device will automatically warn the user when they apply more pressure on a single side using haptic feedback. Along with this, we included the automatic fall detection system using MEMS Sensor, if the sensor reaches its threshold value, it’ll automatically send an Emergency SMS along with their current location to the caretaker/doctors. The exterior has been updated and additionally includes an LED light and switch. The switch will allow the user of the Effective Walker tool to turn it on and off in an easy-to-use way. The Effective Walker device's switch improves its ecological performance by enabling user to remotely turn it off whenever not in use. The system's foundation lies in a network of strategically placed sensors, including gyroscopes, accelerometers, and pressure sensors, meticulously capturing data on the user's body posture and gait patterns. Employing advanced algorithms, the gathered data is processed and analyzed in real-time to evaluate the user's alignment and identify any deviations from the ideal posture. Furthermore, the system facilitates seamless data recording and analysis, enabling healthcare professionals and physiotherapists to access valuable insights on the user's progress and performance. The accumulated data assists in developing personalized rehabilitation plans and tracking the user's improvements over time.

Пилинг-ассоциированные тракции в хирургическом лечении диабетического макулярного отека

Vitreoretinal surgical treatment is indicated for diabetic macular edema (DME) in combination with vitreomacular interface abnormalities. Peeling of the retinal internal limiting membrane (ILM) is often used as part of the treatment. Tight adhesion of the posterior hyaloid membrane and the ILM may be the cause of the intraoperative retinal tractions development. Purpose. To assess the prevalence and impact of transient peeling-associated traction (tPAT) on the results and incidence of complications of surgical treatment of DME using ILM-peeling. Material and methods. As part of the study, a group of 40 patients was divided into 2 comparable subgroups according to the presence of tPAT (1st group — with tPAT, 2nd group — without tPAT). Patients in both groups received surgical treatment — three-port 27 Ga vitrectomy with ILM-peeling in a rounded area with a diameter of up to 2 DD centered on the fovea. ILM-peeling was performed using intraoperative tomographic control (optical coherence tomography). Results. In both groups, anatomical improvement was noted in the form of a decrease in foveal retinal thickness. At the same time, in 1st group there was no improvement in visual acuity, while in 2nd group its statistically significant increase was revealed. The presence of tPAT is associated with a higher incidence of postoperative neurodegenerative changes development of long-term follow-up period — disorganization of retinal inner layers and the formation of lamellar breaks in the fovea. According to correlation analysis, tPAT negatively affects the final value of visual acuity. Conclusion. It has been established that tPAT is a predictor of lower postoperative visual acuity, and is also a risk factor for retinal neurodegenerative changes in the long-term follow-up period. It is promising to evaluate the prevalence of tPAT in larger studies, reveal predictors of tPAT development and measures for their intraoperative prevention. Keywords: vitreoretinal surgery, ILM peeling, dosed fovea-sparing ILM peeling, optical coherence tomography, lamellar macular hole, disorganisation of retinal inner layers, peelingassociated tractions photocoagulation of the retina; long-term results