The compelling role of allopurinol in hyperuricemia-induced epilepsy: Unrecognized like tears in rain.

Epilepsy is a common neurological disease characterized by the recurrent, paroxysmal, and unprovoked seizures. It has been shown that hyperuricemia enhances and associated with the development and progression of epilepsy through induction of inflammation and oxidative stress. In addition, uric acid is released within the brain and contributes in the development of neuronal hyperexcitability and epileptic seizure. Brain uric acid acts as damage associated molecular pattern (DAMP) activates the immune response and induce the development of neuroinflammation. Therefore, inhibition of xanthine oxidase by allopurinol may reduce hyperuricemia-induced epileptic seizure and associated oxidative stress and inflammation. However, the underlying mechanism of allopurinol in the epilepsy was not fully elucidated. Therefore, this review aims to revise from published articles the link between hyperuricemia and epilepsy, and how allopurinol inhibits the development of epileptic seizure.

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy.

Parkinson's disease (PD) is a neurodegenerative disorder of the brain and is manifested by motor and non-motor symptoms because of degenerative changes in dopaminergic neurons of the substantia nigra. PD neuropathology is associated with mitochondrial dysfunction, oxidative damage and apoptosis. Thus, the modulation of mitochondrial dysfunction, oxidative damage and apoptosis by growth factors could be a novel boulevard in the management of PD. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase type B (TrkB) are chiefly involved in PD neuropathology. BDNF promotes the survival of dopaminergic neurons in the substantia nigra and enhances the functional activity of striatal neurons. Deficiency of the TrkB receptor triggers degeneration of dopaminergic neurons and accumulation of α-Syn in the substantia nigra. As well, BDNF/TrkB signalling is reduced in the early phase of PD neuropathology. Targeting of BDNF/TrkB signalling by specific activators may attenuate PD neuropathology. Thus, this review aimed to discuss the potential role of BDNF/TrkB activators against PD. In conclusion, BDNF/TrkB signalling is decreased in PD and linked with disease severity and long-term complications. Activation of BDNF/TrkB by specific activators may attenuate PD neuropathology.

Turmeric Extract-loaded Selenium Nanoparticles Counter Doxorubicin-induced Hepatotoxicity in Mice via Repressing Oxidative Stress, Inflammatory Cytokines, and Cell Apoptosis.

BACKGROUND: Doxorubicin (DOX) is an antitumor anthracycline used to treat a variety of malignancies; however, its clinical use is associated with noticeable hepatotoxicity. Therefore, the current study was designed to delineate if biosynthesized SeNPs with turmeric extract (Tur-SeNPs) could alleviate DOX-induced hepatic adverse effects. METHODS: Mice were orally post-treated with Tur extract, Tur-SeNPs, or N-acetyl cysteine after the intraperitoneal injection of DOX. RESULTS: Our findings have unveiled a remarkable liver attenuating effect in DOX-injected mice post-treated with Tur-SeNPs. High serum levels of ALT, AST, ALP, and total bilirubin induced by DOX were significantly decreased by Tur-SeNPs therapy. Furthermore, Tur-SeNPs counteracted DOX-caused hepatic oxidative stress, indicated by decreased MDA and NO levels along with elevated levels of SOD, CAT, GPx, GR, GSH, and mRNA expression levels of Nrf-2. Noteworthily, decreased hepatic IL-1ß, TNF-α, and NF-κB p65 levels in addition to downregulated iNOS gene expression in Tur-SeNPs-treated mice have indicated their potent antiinflammatory impact. Post-treatment with Tur-SeNPs also mitigated the hepatic apoptosis evoked by DOX injection. A liver histological examination confirmed the biochemical and molecular findings. CONCLUSIONS: In brief, the outcomes have demonstrated Tur loaded with nanoselenium to successfully mitigate the liver damage induced by DOX via blocking oxidative stress, and inflammatory and apoptotic signaling.

Constituents of Stachys plants as potential dual inhibitors of AChE and NMDAR for the treatment of Alzheimer's disease: a molecular docking and dynamic simulation study.

Alzheimer's disease (AD) is a chronic neurodegenerative condition characterized by progressive cognitive impairment. While the formation of ß-amyloid plaques and neurofibrillary tangles are the hallmarks features of AD, the downstream consequence of these byproducts is the disruption of the cholinergic and glutamatergic neural systems. Growing evidence for the existence of interplay between AChE and NMDARs has opened up new venues for the discovery of novel ligands endowed with anticholinesterase and NMDAR-blocking activity. Plants belonging to the stachys genus have been extensively explored for having a broad range of therapeutic applications and have been used traditionally for millennia, to treat various CNS-related disorders, which makes them the ideal source of novel therapeutics. The present study was designed to identify natural dual-target inhibitors for AChE and NMDAR deriving from stachys genus for their potential use in AD. Using molecular docking, drug-likeness-profiling, MD simulation and MMGBSA calculations, an in-house database of biomolecules pertaining to the stachys genus was shortlisted based on their binding affinity, overall stability and critical ADMET parameters. Pre- and post-MD analysis revealed that Isoorientin effectively binds to AChE and NMDAR with various vital interactions, exhibits a stable behavior with minor fluctuations relative to two clinical drugs used as positive control, and displays strong and consistent interactions that lasted for the majority of the simulation. Findings from this study have elucidated the rationale behind the traditional use of Stachys plants for the treatment of AD and could provide new impetus for the development of novel dual-target therapeutics for AD treatment.Communicated by Ramaswamy H. Sarma.

A review of pomegranate supplementation: A promising remedial avenue for Alzheimer's disease.

Neurodegenerative complications, like Alzheimer's disease (AD) exert adverse effects i.e. psychological and physiological in the central nervous system. The synthetic drugs used for these complications have negative effects on body health and therefore natural remedies are a good and targeted approach to counter such complications. Alternatively, fruits and a variety of biochemicals which are an important source of diet, can be used for remedial purposes. Due to the antioxidant properties of polyphenolic compounds, several companies utilize this property to advertise polyphenol-rich beverages. Pomegranate (Punica granatum L.), is one such fruit that is well known for its medical usage due to its antioxidant properties. In the cuurent study a literature search survey was performed on traditional uses, phytochemicals on pomegranate and their medical applications especaily in neurodegenerative deasese using electronic data bases like PubMed, Google Scholar, Scopus, Science Direct Wikipedia and Springer Nature. Based on previous preclinical and clinical studies, pomegranate juice, extracts, and its bioactive constituents have shown many mitigating properties, including suppression of inflammatory cell signaling, reduction in expression of genes associated with oxidative stress as well as pro-inflammatory cytokines in neurons, decreased production of inflammatory and oxidative stress biomarkers and increased expression of endothelial nitric oxide synthase. It also decreases the expression of soluble amyloid protein procurer ß (sAPPß), ß-secretase and carboxyl terminal fragment ß (CTFß). Similarly, during an in-vivo study on APP/PS1 mice, pomegranate supplementation has been shown to impart cognitive aid by the protection of neurons and triggering neurogenesis through anti-inflammatory signaling pathway. In conclusion, pomegranate supplementation can be a promising source of protection against Alzheimer's disease.

Impact of Nutritional Interventions on Alzheimer's Disease: A Systematic Review and Meta-Analysis.

The most prevalent type of dementia, especially in older persons, is Alzheimer's disease (AD), which has clinical signs of progressive cognitive decline and functional impairment. However, new research indicates that AD patients' dietary patterns and nutritional intake could hold the key to staving off some of the complications. Therefore, the primary aim of this investigation was to analyze various dietary patterns and the subsequent impact of the resulting nutritional intake on AD patients. Various online databases (PubMed, Scopus, Web of Science, and Google Scholar) were searched using appropriate keywords, reference searches, and citation searches. The databases were accessed using the search phrases "Alzheimer's disease," "dietary habits," "minerals," "nutritional profile," and "vitamins." Fifteen of the 21 investigations that we selected for our systematic review and subsequent meta-analysis revealed that micronutrient supplementation and some dietary patterns were helpful in alleviating a few of the symptoms of AD, especially with regard to the progression of dementia in the assessed patients. It was shown that dietary interventions and nutritional adjustments can considerably delay the onset of AD and the varying degrees of dementia that often accompany it. However, there were some areas of ambiguity in our findings because a few of the chosen studies did not document any noticeable improvements in the patient's conditions.

The potential therapeutic effect of phosphodiesterase 5 inhibitors in the acute ischemic stroke (AIS).

Acute ischemic stroke (AIS) is a focal neurological disorder that accounts for 85% of all stroke types, due to occlusion of cerebral arteries by thrombosis and emboli. AIS is also developed due to cerebral hemodynamic abnormality. AIS is associated with the development of neuroinflammation which increases the severity of AIS. Phosphodiesterase enzyme (PDEs) inhibitors have neuro-restorative and neuroprotective effects against the development of AIS through modulation of the cerebral cyclic adenosine monophosphate (cAMP)/cyclic guanosine monophosphate (cGMP)/nitric oxide (NO) pathway. PDE5 inhibitors through mitigation of neuroinflammation may decrease the risk of long-term AIS-induced complications. PDE5 inhibitors may affect the hemodynamic properties and coagulation pathway which are associated with thrombotic complications in AIS. PDE5 inhibitors reduce activation of the pro-coagulant pathway and improve the microcirculatory level in patients with hemodynamic disturbances in AIS. PDE5 inhibitors mainly tadalafil and sildenafil improve clinical outcomes in AIS patients through the regulation of cerebral perfusion and cerebral blood flow (CBF). PDE5 inhibitors reduced thrombomodulin, P-selectin, and tissue plasminogen activator. Herein, PDE5 inhibitors may reduce activation of the pro-coagulant pathway and improve the microcirculatory level in patients with hemodynamic disturbances in AIS. In conclusion, PDE5 inhibitors may have potential roles in the management of AIS through modulation of CBF, cAMP/cGMP/NO pathway, neuroinflammation, and inflammatory signaling pathways. Preclinical and clinical studies are recommended in this regard.

Pathogenic Role of Fibrinogen in the Neuropathology of Multiple Sclerosis: A Tale of Sorrows and Fears.

Multiple sclerosis (MS) is an autoimmune demyelinating neurodegenerative disease of the central nervous system (CNS) due to injury of the myelin sheath by immune cells. The clotting factor fibrinogen is involved in the pathogenesis of MS by triggering microglia and the progress of neuroinflammation. Fibrinogen level is correlated with MS severity; consequently, inhibition of the fibrinogen cascade may reduce MS neuropathology. Thus, this review aimed to clarify the potential role of fibrinogen in the pathogenesis of MS and how targeting of fibrinogen affects MS neuropathology. Accumulation of fibrinogen in the CNS may occur independently or due to disruption of blood-brain barrier (BBB) integrity in MS. Fibrinogen acts as transduction and increases microglia activation which induces the progression of inflammation, oxidative stress, and neuronal injury. Besides, brain fibrinogen impairs the remyelination process by inhibiting the differentiation of oligodendrocyte precursor cells. These findings proposed that fibrinogen is associated with MS neuropathology through interruption of BBB integrity, induction of neuroinflammation, and demyelination with inhibition of the remyelination process by suppressing oligodendrocytes. Therefore, targeting of fibrinogen and/or CD11b/CD18 receptors by metformin and statins might decrease MS neuropathology. In conclusion, inhibiting the expression of CD11b/CD18 receptors by metformin and statins may decrease the pro-inflammatory effect of fibrinogen on microglia which is involved in the progression of MS.

Neurological Implications of Vitamin B12 Deficiency in Diet: A Systematic Review and Meta-Analysis.

BACKGROUND: Vitamin B12 is one of the most important B-Vitamins that the human body needs on a daily basis, the lack of which can precipitate several neurological issues. OBJECTIVES: This systematic aimed to investigate the neurological implications of Vitamin B12 deficiency and the effects when B12 levels were corrected in susceptible individuals. METHODS: The databases PubMed-MEDLINE, Web of Science, Cochrane, and Scopus were all searched using pertinent keywords, reference searches, and citation searches. The terms used to access the database were "Cognition", "Dietary patterns", "Neurology", "Nutritional profile", and "Vitamin B12". RESULTS: Vitamin B12 was shown to noticeably improve cognition and other neurological parameters in the short term in older adults and the short-to-medium term in children; however, there was no perceived increase/improvement when the Vitamin was administered in the longer term, either alone or in conjunction with other similar nutritional interventions. CONCLUSION: Vitamin B12's role in the improvement of neurological functions over a long-term period remains somewhat inconclusive to date, as the majority of our selected control trials did not display much correlation between the two factors. However, Vitamin B12 did improve cognition levels in both children and older adults over a short course of administration.

Targeting of neuroinflammation by glibenclamide in Covid-19: old weapon from arsenal.

In coronavirus disease 2019 (Covid-19) era, neuroinflammation may develop due to neuronal tropism of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or associated immune activation, cytokine storm, and psychological stress. SARS-CoV-2 infection and linked cytokine storm may cause blood-brain barrier (BBB) injury through which activated immune cells and SARS-CoV-2 can pass into the brain causing activation of glial cells with subsequent neuroinflammation. Different therapeutic regimens were suggested to alleviate Covid-19-induced neuroinflammation. Since glibenclamide has anti-inflammatory and neuroprotective effects, it could be effective in mitigation of SARS-CoV-2 infection-induced neuroinflammation. Glibenclamide is a second-generation drug from the sulfonylurea family, which acts by inhibiting the adenosine triphosphate (ATP)-sensitive K channel in the regulatory subunit of type 1 sulfonylurea receptor (SUR-1) in pancreatic ß cells. Glibenclamide reduces neuroinflammation and associated BBB injury by inhibiting the nod-like receptor pyrin 3 (NLRP3) inflammasome, oxidative stress, and microglial activation. Therefore, glibenclamide through inhibition of NLRP3 inflammasome, microglial activation, and oxidative stress may attenuate SARS-CoV-2-mediated neuroinflammation.

Role of MicroRNAs in Cardiac Disease with Stroke in Pregnancy.

Pregnancy-related cardiovascular disease with stroke remains a considerable source of higher maternal morbidity and mortality occurs in periods of pregnancy, delivery, and postpartum. It is essential to counsel the mother before pregnancy by an expert cardiologist and obstetric team to discuss any event related to preexistent cardiac or past preeclampsia for estimation of maternal and fetal risks. In pregnancy, the cardiac state includes hypertensive disorders, ischemic heart disease, valvular disease, and postpartum stroke. The incidence of stroke is increasing in pregnancy, particularly in postpartum, and its strong relationship with hypertensive disorders of pregnancy (preeclampsia). The combined cardiologist and obstetrics team requires during pregnancy mainly due to the approach to the management of a cardiac disease that subsequently prevents stroke postpartum. Therefore, a general perception of cardiac disease during pregnancy, delivery, and postpartum should be a core knowledge extent for all cardiovascular and clinicians. Many studies provided linked that deregulation of microRNAs (miRNAs) in maternal circulation and placenta tissue may development of pregnancy complications including preeclampsia considered a diagnostic marker. The desire of this review provides a detailed outline of current knowledge and dealing in this field with strength on the physiological changes during pregnancy.

Prevalence and prediction of pressure ulcers in admitted stroke patients in a tertiary care hospital.

Pressure ulcer (PU) is a localized injury to the skin or underlying tissues usually over a bony prominence, which results due to pressure or pressure in combination with shear. It is an expensive health care problem that have deterring impact on the length of hospitalization and cause extra nursing care time. Moreover, PUs negatively impacts patients' health related quality of life. High PUs prevalence figures were found in specialized hospital units such as intensive care unit (ICU), orthopedics, surgery, and also in stroke patients in medical units. The major purpose of this study is to assess the frequency of pressure ulcers in stroke patients at Ayub teaching hospital. The methodology used for carrying out the research was cross-sectional study conducted during months of September, October, and November 2020. Questionnaire was used to collect the data and well-informed written consent was taken from the patients. A total of 120 stroke patients were initially included with the intention to study the frequency of PUs among them. Different age groups were taken but majority (48.3%) belonged to the age group 31-60 years. Maximum patients were hypertensive (65%), while few of them were diabetic (35%). From the results of proposed work, it is found that out of 120 stroke patients, 75.8% presented with ischemic stroke while 24.2% presented with hemorrhagic stroke. 8.3% that is 10 out of 120 stroke patients developed pressure ulcers of grade 1 (1.7%), grade 2 (1.7%), grade 3 (2.5%), and grade 4 (2.5%) mostly in the sacral region (6.7%) and also on ankle (0.8%), and shoulder (0.8%) respectively. Patients in the study group had unsatisfactory hygiene (6.7%) were malnourished (11.7%) and were not using preventive mattresses (79.2%). Those at the risk of developing pressure ulcers were not being repositioned (6.7%) and did not had awareness (10%). Prevention and treatment used in ward is 100%. Conclusively, the frequency of pressure ulcers in stroke patients was determined to be 8.3% and the most frequent localization was sacrum. The PU care in this hospital is appropriate but still could be improved further by improving risk assessment, prevention specially use of air mattress and patient education regarding PUs. The main objective of the study is to identify the frequency of PUs in stroke patients and to highlight various factors that would avoid PUs development.

Knowledge, attitude and practice of schoolteachers towards students with epilepsy in Al-Jouf, Saudi Arabia.

BACKGROUND: Epilepsy is a common disorder in which brain activity becomes abnormal that causes recurrent seizures or periods of jerky movement of the whole body. Immediately after a seizure, people are often transiently confused, weak and unable to communicate. OBJECTIVE: This study assesses the knowledge, attitude, and practice (KAP) of school teachers towards an epileptic child. METHODS: This cross-sectional study was conducted among primary and secondary school teachers from different schools in Sakaka, Domat Al-Jandal, Al-Qurayyat, Tabarjal Northern region of Aljouf, Saudi Arabia. They were assessed on their KAP toward students with epilepsy using a self-administrated questionnaire. RESULTS: 306 respondents participated and completed the questionnaire. The practice was poor among the teachers. Practice scores were significantly different among the male and female teachers. Teachers would do the following to the seizing child: 159 (52%) would pull the child's tongue out (p-value 0.012), 66 (21.6%) would put a spoon in the mouth (p-value 0.055), 43 (14.1%) would remove any tight clothes (p-value 0.009) and 244 (79.7 %) would take the child to the hospital (p-value 0.029). There were significant differences among senior teachers and those with longer years of teaching experience: 83.6% of teachers with > 20 years of teaching experience think that the student with epilepsy has no need of a special classroom (P = 0.053), 89.6% of those with > 20 years of teaching experience said that they did not move the child during seizure in comparison with less years of teaching experience (p = 0.048), in which 97% of those with experience > 20 years said that they would ensure normal breathing (p = 0.015). CONCLUSION: The majority of Aljouf schoolteachers were adequately knowledgeable about students with epilepsy, but they need more information about the correct way of practice towards the student with epilepsy.

Public awareness of first-aid management of seizures in Saudi Arabia.

BACKGROUND: First aid measures in cases of epileptic seizures are crucial. Misconceptions about seizure first-aid measures are probably common. Most of the previous data focused on teachers and healthcare providers. The objective of this study was to assess the awareness of seizure first-aid measures and their associated factors in a community sample in Saudi Arabia. METHODS: A cross-sectional study was carried out using an online questionnaire between July 2020 and February 2021. Those who had never heard of epilepsy and healthcare workers were excluded. Overall and individual scores were calculated for first-aid measures during and after the seizures as well as calling the ambulance. RESULTS: A total of 1542 participants were included in the study. The overall awareness score of seizure first-aid measures was 57.3%. The awareness of the need to call the ambulance in special circumstances was the highest individual score (78.3%), followed by measures after the seizure (54.2%), and finally measures during the seizure (48.4%). For the latter, the awareness of injury prevention measures was the highest (74.9%), while the awareness of treatment options was the lowest (12.2%). Overall awareness score was significantly higher in older age (p = 0.015), female gender (p < 0.001), divorced status (p = 0.014), knowing someone with epilepsy (p < 0.001), attending a course or workshop about seizure first-aid (p < 0.001), watching a video on seizure first-aid on any platform (p < 0.001), and having basic life support training (p < 0.001). CONCLUSIONS: The awareness of seizure first-aid measures is still inadequate among the public in Saudi Arabia. The current finding underscores the importance of simulation videos on social media and/or field-training campaigns to improve the public awareness of seizure first-aid measures.

Brain Tumor/Mass Classification Framework Using Magnetic-Resonance-Imaging-Based Isolated and Developed Transfer Deep-Learning Model.

With the advancement in technology, machine learning can be applied to diagnose the mass/tumor in the brain using magnetic resonance imaging (MRI). This work proposes a novel developed transfer deep-learning model for the early diagnosis of brain tumors into their subclasses, such as pituitary, meningioma, and glioma. First, various layers of isolated convolutional-neural-network (CNN) models are built from scratch to check their performances for brain MRI images. Then, the 22-layer, binary-classification (tumor or no tumor) isolated-CNN model is re-utilized to re-adjust the neurons' weights for classifying brain MRI images into tumor subclasses using the transfer-learning concept. As a result, the developed transfer-learned model has a high accuracy of 95.75% for the MRI images of the same MRI machine. Furthermore, the developed transfer-learned model has also been tested using the brain MRI images of another machine to validate its adaptability, general capability, and reliability for real-time application in the future. The results showed that the proposed model has a high accuracy of 96.89% for an unseen brain MRI dataset. Thus, the proposed deep-learning framework can help doctors and radiologists diagnose brain tumors early.

Mycoplasma pneumoniae and Schistosoma mansoni co-infection in a young patient with extensive longitudinal acute transverse myelitis.

INTRODUCTION: Acute transverse myelitis is an uncommon inflammatory, intramedullary, disorder of the spinal cord. Spastic paraplegia, impaired sphincter functions, and sensory loss, with sensory level, are the clinical manifestations of this devastating disorder. The utilization of magnetic resonant imaging (MRI) contributes to the surge in the diagnosis of more ATM cases. Although the causes of ATM are numerous, both Mycoplasma pneumoniae and Schistosoma mansoni are uncommon causes and their co-existence in the same patient has not been reported before in Saudi Arabia. CASE: We report a 25-year-old ATM male patient presented with a history of sudden onset severe low back pain. Within four hours from the onset of the back pain, he became completely paraplegic with impaired functions of the bowel and urinary bladder sphincter. Furthermore, he lost all modalities of sensory functions in the lower limbs. His examination revealed spastic complete paraplegia with sensory level at T6. Clinical neurological examination revealed normal upper limbs and brain functions. The MRI of the cervico-dorsal spine showed extensive longitudinal hyperintense lesion extending from the upper cervical segments to the lower dorsal segments (extensive longitudinal transverse myelitis). A post-infectious immune-mediated predisposition was highly suspected due to the very high titers of anti-Mycoplasma pneumoniae IgM and IgG that were detected. The immunosuppressant therapy did not improve his paraplegia. A spinal cord biopsy revealed the presence of several Schistosoma mansoni ova surrounded by chronic inflammatory reactions and reactive gliosis. CONCLUSIONS: Both Mycoplasma pneumoniae and Schistosoma mansoni should be investigated in cases with extensive longitudinal ATM.