Proflactic effects of rosmarinic acid on spinal cord injury in rats
Spinal cord injury (SCI) causes various neurological consequences that disrupt the structure of axons. The C/EBP Homologous Protein (CHOP) acts in neuronal death by apoptosis has been demonstrated in experimental models. Rosmarinic acid (RA) is a phenolic compound used for therapeutic purposes in many diseases. In this study, we investigated the therapeutic effect of Rosmarinic acid application on inflammation and apoptotic development after spinal cord injury.
Audiological evaluation of the cochlear nerve with brainstem evoked response audiometry in patients with COVID-19
In this clinical study, it was aimed to prospectively evaluate the cochlear nerve with brainstem evoked response audiometry (BERA) in terms of audiological ailments in patients with COVID-19. Although the relationship of COVID-19 with tinnitus and hearing loss has been investigated since the day this infectious respiratory disease emerged, its relationship with BERA has not been fully demonstrated from a neurological perspective.
Evaluation of daily Laurus nobilis tea consumption on anxiety and stress biomarkers in healthy volunteers
Laurus nobilis is known in the field of herbal medicine and in vitro studies for its antibacterial, antifungal, anti- diabetes, and anti-inflammatory beneficial effects. Laurus nobilis tea consumption was investigated with regard to its effects on anxiety and stress in healthy individuals, measured by subjective tools and by plasmatic cortisol levels. The study included thirty healthy Tunisian volunteers aged between 20 and 57 years consuming Laurus nobilis infusion, prepared from 5g of dried Laurus nobilis leaves in 100 ml boiled water, once a day during 10 days. Plasma concentrations of serum cortisol were measured before Laurus nobilis consumption and at the end of the experiment. Laurus nobilis tea consumption significantly decreased the concentration of plasmatic cortisol ([cortisol] D0= 93.5± 43.01ng/mL, D11=72.23± 25.37, p=0.001). A statistically significant decrease in PSS and STAI scores (p=0.006 and p=0.002 respectively) was also noted.These findings highlight the decrease in blood cortisol levels, which means a possible positive effect on reducing the risk of stress related-diseases in healthy volunteers consuming Laurus nobilis tea. However, more powerful studies with extended treatment periods are required.
Effects of thymoquinone on spinal cord injury in rats
Spinal cord injury (SCI) is a condition that causes disturbances in normal sensory, motor, and autonomic functions. During SCI, damages occur such as, contusion, compression, distraction. The aim of this study was to investigate effects of the antioxidative thymoquinone on neuron and glia cells in SCI biochemically, immunohistochemically and ultrastructurally.
The potential effects of nutrients and light on autophagy-mediated visual function and clearance of retinal aggregates
Increasing findings indicate that a dysfunction in the autophagy machinery is common during retinal degeneration. The present article provides evidence showing that an autophagy defect in the outer retinal layers is commonly described at the onset of retinal degeneration. These findings involve a number of structures placed at the border between the inner choroid and the outer retina encompassing the choriocapillaris, the Bruch's membrane, photoreceptors and Mueller cells. At the center of these anatomical substrates are placed cells forming the retinal pigment epithelium (RPE), where autophagy seems to play most of its effects. In fact, a failure of the autophagy flux is mostly severe at the level of RPE. Among various retinal degenerative disorders, age-related macular degeneration (AMD) is mostly affected by a damage to RPE, which can be reproduced by inhibiting the autophagy machinery and it can be counteracted by the activation of the autophagy pathway. In the present manuscript evidence is provided that such a severe impairment of retinal autophagy may be counteracted by administration of a number of phytochemicals, which possess a strong stimulatory activity on autophagy. Likewise, natural light stimulation administered in the form of pulsatile specific wavelengths is capable of inducing autophagy within the retina. This dual approach to stimulate autophagy is further strengthened by the interaction of light with phytochemicals which is shown to activate the chemical properties of these natural molecules in sustaining retinal integrity. The beneficial effects of photo-biomodulation combined with phytochemicals is based on the removal of toxic lipid, sugar and protein species along with the stimulation of mitochondrial turn-over. Additional effects of autophagy stimulation under the combined effects of nutraceuticals and light pulses are discussed concerning stimulation of retinal stem cells which partly correspond to a subpopulation of RPE cells.
Histopathological evaluation of IBA-1, GFAP activity in the brain cortex of rats administered cadmium chloride
Purpose: This study aims to evaluate the changes in brain tissue and blood-brain barrier due to oxidative stress during cadmium (Cd) poisoning by biochemical, histopathological, and immunohistochemical methods. Methods: 170-190 g weighing eight-week-old female Wistar albino rats were divided into two groups (control and experimental), with 7 animals in each group. Experimental group rats were given 2 mg/kg/day powdered cadmium chloride dissolved in water intraperitoneally every day for two weeks. Biochemical, histopathological and immunohistochemical examination was performed. Results: It was seen that brain malondialdehyde (MDA) levels increased significantly, and glutathione (GSH) and catalase (CAT) activity levels decreased. In addition to degeneration in some pyramidal cells and glial cells, deformity, and picnosis in the nucleus, dilation of the meninges and cortex vessels, and inflammation around the blood vessels were observed. An increase was found in ionized calcium binding adaptor molecule 1 (IBA-1) expression in microglia cells and degenerative endothelial cells, and increased glial fibrillary acidic protein (GFAP) expression was observed in astrocytes and degenerate neurons. Conclusions: It has been shown that cadmium toxicity may cause microgliosis and astrogliogenesis by inducing cytokine production due to cell degeneration, vascularity, and inflammation in the brain cortex and by affecting microglia, astrocytes cells.
The effect of vitamin E supplementation on brain tissue element levels in epileptic rats
The aim of this study was to investigate how the application of vitamin E affected the levels of chemical elements in the brain tissues of epilepsy-induced rats. The sample of 40 adult male rats was separated into 4 equal groups: Group 1: control, Group 2: vitamin E; Group 3: penicillin to promote epileptic form activity and Group 4: penicillin + vitamin E. After three months of treatment, an Atomic Absorption Spectrophotometer was used to analyze the presence of the elements in brain tissue sections (brain, brainstem, cerebellum) of the decapitated animals. The levels of magnesium in the groups that received vitamin E (G2 and 4) were significantly higher than in the control group (G1) and the first epilepsy group (G3) (p.05).Chrome and zinc levels in brain, brainstem, and cerebellum tissue of the two epilepsy groups (G3-4) decreased significantly compared to the control group (G1) and the vitamin E group (G2) (p.05). The levels of copper in the brainstem and lead in the cerebellum of the first epilepsy group (G3) were higher than in all other groups (p.05). The findings showed that the application of vitamin E in experimental epilepsy may have a limited effect on element metabolism in brain tissue. A decline in zinc levels in the brain, brainstem and cerebellum tissues in epilepsy groups constitutes another result of our study. This should be examined further to determine whether decreased levels of zinc play a role in epilepsy pathogenesis.
Noradrenergic substrates sensing light within brainstem reticular formation as targets for light-induced behavioral and cardiovascular plasticity
The occurrence of pure light exerts a variety of effects in the human body, which span from behavioral alterations, such as light-driven automatic motor activity, cognition and mood to more archaic vegetative functions, which encompass most organs of the body with remarkable effects on the cardiovascular system. Although empirical evidence clearly indicates occurrence of these widespread effects, the anatomical correlates and long-lasting changes within putatively specific neuronal circuitries remain largely unexplored. A specific role is supposed to take place for catecholamine containing neurons in the core of the brainstem reticular formation, which produces a widespread release of noradrenaline in the forebrain while controlling the vegetative nervous system. An indirect as well as a direct (mono-synaptic) retino-brainstem pathway is hypothesized to rise from a subtype of intrinsically photosensitive retinal ganglion cells (iPRGCs), subtype M1, which do stain for Brn3b, and project to the pre-tectal region (including the olivary pre-tectal nucleus). This pathway provides profuse axon collaterals, which spread to the periacqueductal gray and dorsal raphe nuclei. According to this evidence, a retino-reticular monosynaptic system occurs, which powerfully modulate the noradrenergic hub of reticular nuclei in the lateral column of the brainstem reticular formation. These nuclei, which are evidenced in the present study, provide the anatomical basis to induce behavioral and cardiovascular modulation. The occurrence of a highly interconnected network within these nuclei is responsible for light driven plastic effects, which may alter persistently behavior and vegetative functions as the consequence of long-lasting alterations in the environmental light stimulation of the retina. These changes, which occur within the core of an archaic circuitry such as the noradrenaline-containing neurons of the reticular formation, recapitulate, within the CNS, ancestral effects of light-driven changes, which can be detected already within the retina itself at the level of multipotent photic cells.
In search for a neuropsychological marker of ADHD: findings from incidental memory testing
This paper reports on a study where the incidental memory of 18 children with ADHD and 18 typically developing peers was assessed by means of a conventional two-phase recognition memory test. In the study phase participants were required to categorize as a living or non-living a set of 64 stimuli from 8 semantic categories. In the test phase, they were required to recognize "target" (i.e., stimuli from the first set) from "non-target" stimuli. Children with ADHD were overall less accurate and much slower than TD controls in identifying both living and non-living items. Moreover, while most of TD participants made very few, if any, errors, only 7 out of 18 participants with ADHD scored near ceiling, and 2 of them scored below chance level. Following the Signal Detection Theory approach, the participants' performance on the test phase was scored in terms of d prime (d') values. Children with ADHD had lower d' indexes compared to controls both for living and non-living stimuli, although this difference did not reach statistical significance. More interestingly, the variability of the d' values was higher in the ADHD compared to Controls. Taken together, findings from this study indicate that at least some of the children with ADHD have a genuine impairment in processing visual stimuli. More generally, these results cast doubts on the idea that ADHD represents a stable nosographic entity.
Spreading depolarization: A phenomenon in the brain
In 1944, the physiologist Leão while studying epilepsy in the rabbit noticed a sudden temporary cessation of electrocorticographic (ECoG) activity accompanied with a large negative slow potential change recorded by extracellular electrodes, that is later known as spreading depolarizations (SDs). The depression of the brain electrical activity was slowly propagating through the cerebral cortex. The mechanism of propagation is still controversial. SDs and seizures are following each other interchangeably, yet the puzzle needs more investigation to be clarified. SDs have an obvious effect on blood-brain barrier integrity mainly through transcellular and paracellular routs, but not much known about that especially following traumatic brain injury (TBI). The cortical spreading depolarization (CSD) and the depression of brain activity have been recognized following a variety of neurological diseases and brain injuries. CSD has been studied in animal models and recently in humans, and it has been recognized and described as a massive neuronal depolarization accompanied with high level of disturbances in transmembrane ion gradients and significant changes in cerebral blood flow (1-3). Although there is a considerable amount of literatures on SD have been done since 1944, but the biophysical mechanism of SD, the long term effect on the brain structures and functions, and it is role in different disorders are still incompletely understood.Here, we summarize the history of spreading depolarization and the most accepted hypothesis for mechanism of initiation and propagation of that phenomenon. Most importantly, we present the most updated research on the relationship and interaction between spreading depolarization and traumatic brain injuries, seizure, blood-brain barrier, neurovascular coupling, and other neurological conditions. Learning more about the spreading depolarization will increase our understanding about that phenomenon and may explain its association with different clinical presentations.
Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes
The present manuscript stems from evidence, which indicates that specific wavelength produce an activation of the autophagy pathway in the retina. These effects were recently reported to synergize with the autophagy-inducing properties of specific phytochemicals. The combined administration of photo-modulation and phytochemicals was recently shown to have a strong potential in eliciting the recovery in the course of retinal degeneration and it was suggested as a non-invasive approach named "Lugano protocol" to treat age-related macular degeneration (AMD). Recent translational findings indicate that the protective role of autophagy may extend also to acute neuronal injuries including traumatic neuronal damage. At the same time, very recent investigations indicate that autophagy activation and retinal anatomical recovery may benefit from sound exposure. Therefore, in the present study, the anatomical rescue of a traumatic neuronal loss at macular level was investigated in a patient with idiopathic macular hole by using a combined approach of physical and chemical non-invasive treatments. In detail, light exposure was administered in combination with sound pulses to the affected retina. This treatment was supplemented by phytochemicals known to act as autophagy inducers, which were administered orally for 6 months. This combined administration of light and sound with nutraceuticals reported here as Advanced Lugano's Protocol (ALP) produced a remarkable effect in the anatomical architecture of the retina affected by the macular hole. The anatomical recovery was almost complete at roughly one year after diagnosis and beginning of treatment. The structural healing of the macular hole was concomitant with a strong improvement of visual acuity and the disappearance of metamorphopsia. The present findings are discussed in the light of a synergism shown at neuronal level between light and sound in the presence of phytochemicals to stimulate autophagy and promote proliferation and neuronal differentiation of retinal stem cells.
Combined therapy (Rho-A-kinase inhibitor and chitosan/collagen porous scaffold) provides a supportive environment for endogenous regenerative processes after spinal cord trauma
Due to the complexity of pathological processes in spinal cord injury (SCI), it is increasingly recognized that combined strategies are more effective than single treatments. The aim of the present study was to enhance neural tissue regeneration and axon regrowth using Rho-A-kinase inhibitor (Y-27632) in a rat SCI model (Th9 compression) and to bridge the lesion with a chitosan/collagen porous scaffold (ChC-PS) applied two weeks after SCI. In addition, to see the synergic effect of Y-27632 and ChC-PS, we combined these single therapeutic strategies to enhance the regenerative capacity of injured spinal cord tissue. The animals survived eight weeks. Application of Y-27632 modulated the inhibitory milieu by specifically targeting gray and white matter integrity, glial fibrillary acidic protein (GFAP)-immunoreactivity, and the outgrowth of neurofilaments and growth-associated protein-43 (GAP-43) immunoreactive axons across the lesion sites, leading to significant positive functional outcome from day 20 to 56. Compared to single treatments, combined Y-27632/ChC-PS therapy was more effective in neurofilaments and GAP-43 expression and GFAP immunoreactivity in the perilesional area of dorsal, lateral and ventral columns, and in enhancing the gray and white matter integrity throughout the cranio-caudal extent. The findings indicate that combined therapy provides a supportive environment for endogenous regenerative processes.
The influence of mandibular stretching on athletes subjected to high intensity workout
The use of oral appliances is considered effective in improving sport performance. Jaw clenching or stretching, improved breathing or positioning of the jaw have been proposed to explain the improvement. In this study, we reported the effects of regularly practiced mandibular stretching at submaximal opening of the jaw in Crossfit athletes. Seventeen test subjects undergoing mandibular stretching (MS) showed significantly reduced (p0.001) performance time in a high-intensity workout measured before and after seven days of 10-minutes stretching practiced twice daily, while no improvement was observed in control subjects who did not perform the stretching. Additionally, blood lactate levels appeared to recover more quickly in MS subjects.Crossfit is a type of training regimen that pushes the limits of bodily recovery processes. Jaw stretching, eliciting the trigeminocardiac reflex (a reflex decrease in heart rate and blood pressure following trigeminal stimulation) and central oxygen-conserving mechanisms could help relieve post-training stress and improve training recovery.
Not all sales performance is created equal: personality and interpersonal traits in inbound and outbound marketing activities
A long tradition of research has shown that personality traits, such as extraversion and agreeableness, and interpersonal constructs better predict job performance with a tacit but not explicit distinction in sales marketing activities. In this contribution, we aim to understand the role of job-related and interest data, interpersonal, and personality traits in affecting either inbound or outbound marketing activities and the overall sales performance. An original questionnaire integrates the interpersonal traits and personality factors reported in the literature in sales marketing activities (independent variables). The results were matched with the individual job-related and interest data (control variables) and sales performance (criterion variables) - expressed as the total number of closed contracts over the inbound/outbound related contacts of employees with responsibility in marketing activities for a large banking group. We are able to identify the relevant predictors of sales performance by creating full binary trees using control and independent variables in conditional inference forests and variable importance index measures. Higher performers in either inbound or outbound marketing activities rely on distinct personality sub-traits, which have fundamentally essential implications for interpersonal functioning, and personal data when agreeableness is central to the ability to function effectively in the interpersonal realm of sales activity.
Flow cytometric analysis of CD4 and T-lymphocytes of chronic amphetamine and alcohol abuse
Drug and alcohol abuse has significant negative impacts on individuals' life, health status and communities. They have also been implicated immunity system diseases. Therefore we aim to investigate the impact of chronic amphetamine abuse or co-abuse of alcohol with amphetamine on immunity, especially CD3 T cells, as well as the response of CD4 and CD8 T cells.
The neurobiology of nutraceuticals combined with light exposure, a case report in the course of retinal degeneration
The present article presents a case report and discusses the neurobiology underlying the potential neuro-repair induced by combined administration of phytochemicals in a patient undergoing photo-bio-modulation (PBM), which improves anatomical and clinical abnormalities in the course of age-related macular degeneration (AMD). After combined treatments the patient with nutraceuticals and PBM had noticeable improvement of retinal tissue with excellent vision for her age and no worsening of corneal guttae, which was present at the time of diagnosis. The present treatment was tailored, based on translational evidence, to improve the autophagy pathway, which is a key determinant in the onset and progression of AMD. In fact, treatment with specific patterns of light exposure combined with specific phytochemicals, may synergize in improving the microanatomy of the retina by restoring its neurobiology. The combination of light exposure, at selective wavelengths, with the effects produced by the intake of specific phytochemicals to treat AMD is reported here as "Lugano Protocol". Such a clinical protocol represents an "in progress" development backed up by translational research. In fact, recent evidence indicates that, specific phytochemicals, when administered in combination may promote anatomical and functional integrity within the retina. These in turn synergize with analogous effects produced by specific wavelengths, when administered at specific time intervals. The synergism between specific light and combined phytochemicals is discussed at molecular level, where recent data indicate how these treatments, when delivered according to specific patterns, may enhance autophagy in the retina. The improvement of retinal morphology and visual acuity, observed in this case report is thoroughly discussed in the light of the key role of autophagy in regulating the integrity of the retinal epithelium. Despite exciting, and consistent with translational evidence, the clinical report of a disease modifying effect during AMD owns the inherent limit of a case report, which requires wide validation in large number of patients. The potential effectiveness of "Lugano protocol" may apply to other types of retinal degenerations, where common alterations in the autophagy pathway do occur. Thus, such a therapeutic approach may extend to a common late stage of retinal trans-synaptic degeneration, where maladaptive plasticity during several types of retinal degenerative disorders eventually converge.
The Effect of 2 Weeks of Naringenin on AQP4, IL-2 and DNA Damage in Brain Ischemia Reperfusion in Rats
The aim of this study was to determine the effect of different doses of naringenin (NAR) administration for 2 weeks in rats on brain Aquaporin-4 (AQP4), interleukin-2 (IL-2) and 8-Hydroxydeoxyguanosine (8-OhdG) levels in brain ischemia-reperfusion. Experimental groups were formed as follows; 1-Control; 2-Sham Control; 3 Ischemia/ Reperfusion (I/R); 4-Naringenin (Naringenin 50) + I/R; 5-Naringenin (naringenin 100) + I/R. I/R was performed as 1 hour occlusion of the carotid arteries (ischemia) followed by 1 hour reperfusion. Naringenin was supplied for 2 weeks by intraperitoneal. At the end of the experiment, AQP4, IL-2 and 8-OHdG levels were determined in the brain frontal cortex tissue taken from animals killed under anesthesia. AQP4, IL-2 and 8-OHdG levels increased significantly in I/R group. However, both 50 mg/kg and 100 mg/kg two-week administration of naringenin significantly decreased these increased parameters (P 0.001).The results of the study show that intraperitoneal administration of naringenin for two weeks in rats may prevent the damage caused by brain ischemia-reperfusion.
Surgical management of sporadic hemangioblastomas located in the posterior fossa of brain
Hemangioblastomas (HBs) are highly vascular tumors, constituting 2%-3% of central nervous system (CNS) tumors. Surgery is a treatment option for HBs. The purpose of this study was to evaluate the demographic, clinical, and radiological findings of patients with HBs who were operated on via microsurgical technique at our clinic and to determine the findings specific to HBs and evaluate their pathological findings and confirmation.
Retinal Degeneration Following Chronic Administration of the Parkinsonism-Inducing Neurotoxin MPTP
During late stages, retinal degenerative disorders affecting photoreceptors progress independently from the specific disease trigger. In fact, a number of detrimental consequences occur downstream of photoreceptors, which are triggered by the loss of photoreceptors themselves. Such downstream anatomical alterations were originally thought to be compensatory events aimed to restore retinal function. At present, these phenomena are deciphered as detrimental effects and the term retinal degeneration is used to indicate the loss of cells and architecture within the inner retina as a consequence of damage to photoreceptors. In the process of testing a photoreceptor-dependent downstream spreading of neurodegeneration we applied a neurotoxin mimicking Parkinson's disease (PD), 1-methyl, 4-phenyl, 1,2,3,6-tetrahydropyridine (MPTP). Chronic MPTP administration produces degeneration within the mouse retina. This is evident by apoptosis quite circumscribed to photoreceptors, which is reminiscent of most phenotypes of retinal degeneration. Retinal pathology following plain HE histochemistry is more widespread with delamination and loss of neuronal packaging in the inner retina. The retinal damage is characterized by a marked synucleinopathy mostly within retinal ganglion cells. In contrast, dopamine-containing structures are intact while norepinephrine is significantly reduced. Despite the involvement of the retina in PD is documented, no study so far analyzed the onset of a synucleinopathy and a degenerative process mimicking what is now recognized in typical retinal degeneration. The present data provide a novel vista on the reciprocal role of the retina in neurodegenerative disorders.
Dual function of Selenium nanoparticles: Inhibition or induction of lysozyme amyloid aggregation and evaluation of their cell based cytotoxicity
Aberrant protein aggregation and the formation of amyloid deposits are associated with numerous neuro- and non-neurodegenerative disorders. Thus, one potential strategy is to eliminate these deposits by halting amyloid aggregation. Selenium nanoparticles (Se-NPs) have great potential in biomedicine for various therapeutic and diagnostic purposes and also have the ability to inhibit amyloid fibrillation. Herein, Hen Egg White Lysozyme (HEWL) was chosen as a protein model, and rod-like Se-NPs with diameters ranging from 90 to 120 nm were synthesized and the influence of shape and concentration of the particles on HEWL fibrillation was investigated. The effect of the nanoparticles on HEWL amyloid formation was analyzed using thioflavin T and Congo red binding assays, atomic force microscopy, and cytotoxicity assays. In the present study, it has been observed that these particles have a dual function in various concentrations. Using lower concentrations of Se-NPs ranging from 3-30 μg/ml, the Thioflavin T (ThT) fluorescence intensity decreased significantly by 60%, with an increased lag time compared to that of the control. While HEWL fibrillation substantially increased upon co-incubation with a higher concentration of these particles (300-2400μg/ml), and these results were verified by AFM, Congo red, and MTT assay. We showed that inhibitory or inductive influences of Se-NPs on the hen egg-white lysozyme (HEWL) amyloid aggregation are achieved via different independent mechanisms. These results demonstrate that dual-activity of Se-NPs might be a valuable targeting system for inhibiting amyloid aggregation, and thus, may play a useful role in new therapeutic and diagnostic strategies for amyloid-related disorders.
Learning effect and repeatability of stabilometric measurements: "standard" vs. usual foot placement
The existence of a learning effect by which subjects progressively reduce body sway over the course of repetitive stabilometric measurements is currently debated. Also, the position and orientation of the feet on the platform can have a substantial influence on the outcome measurements. The aim of the present work was to assess the effect of feet positions on mean total velocity (V) of the center of pressure and the area (AR) covered by its displacements during quiet standing. A group of 35 healthy young subjects was examined during two successive sessions consisting of five recordings with their feet placed either in the recommended (standard, SP) or their usual most comfortable (UP) position. Results show a slight decreasing trend that failed to be statistically significant checked with Friedman's ANOVA (SP AR, χ2(4)=6.10, p=0.19 and V, χ2(4)=8.66, p=0.07 and UP AR, χ2(4)=2.32, p=0.68 and V, χ2(4)=1.19, p=0.88). Nonetheless, values of AR and V showed a notable decrement especially evident in the SP exam reaching, respectively, 24% and 11% from baseline, whereas variability measured by the coefficient of variation was the same in the two exams. Given the results, a learning effect should not be ruled out with confidence. Also, usual foot placement would be preferable to avoid this effect. Further research is needed to take into consideration the great variability of stabilometric measurements and the fact that different subjects could adapt more readily to the test conditions than others.