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Traumatic brain injury (TBI) is a debilitating acquired neurological disorder that afflicts nearly 74 million people worldwide annually. TBI has been classified as more than just a single insult because of its associated risk toward various long-term neurological and neurodegenerative disorders. This risk may be triggered by a series of postinjury secondary molecular and cellular pathology, which may be dependent on the severity of the TBI. Among the secondary injury mechanisms, neuroinflammation may be the most crucial as it may exacerbate brain damage and lead to fatal consequences when prolonged. This Review aimed to elucidate the influence of neuroinflammatory mediators on the TBI functional and pathological outcomes, particularly focusing on inflammatory cytokines which were associated with neuronal dysfunctions in the acute and chronic stages of TBI. These cytokines include interleukins (IL) such as IL-1(beta)β, IL-4, IL-6, IL8, IL-10, IL-18, IL-33 and tumor necrosis factor alpha (TNF-α), which have been extensively studied. Apart from these, IL-2, interferon gamma (IFN-γ), and transforming growth factor-beta (TGF-β) may also play a significant role in the pathogenesis of TBI. These neuroinflammatory mediators may trigger a series of pathological events such as cell death, microglial suppression, and increased catecholaminergic activity. Interestingly, in the acute phase of TBI, most of these mediators may also play a neuroprotective role by displaying anti-inflammatory properties, which may convert to a pro-inflammatory action in the chronic stages post TBI. Early identification and treatment of these mediators may help the development of more effective treatment options for TBI.

Background:Aside from its pervasiveness, whereby it affects as much as 20% of the world's population, depression continues to be one of the most crucial psychiatric problems due to the loss of power it causes by disrupting daily life functioning, containing economic consequences, and having a high suicidal tendency. Major depression (MD) is a systemic and multifactorial disorder involving complex interactions between genetic predisposition and disturbances of various molecular pathways.Objectives:In our current study, we aimed to identify the proteins obtained from serum samples that change during depression with the MD model.Methods:The MD model was applied through the forced swim test in rats. 14 Winstar Albino male rats were divided into two equal groups as follows: depression and control groups. Serum samples were separated by chromatographic methods and then compared with two-dimensional (2D) electrophoresis.Results:A total of 9 potential diagnostic protein sequences were identified, which were distinguished with computer software. During the last phase of the study, the Matrix-Assisted Laser Desorption/ Ionization – Time of Flight (MALDI-TOF) analysis, the previous expression sequences identified among the groups were determined and classified. By comparing protein expressions, it was concluded that 9 different points could be used together as a potential biomarker.Conclusion:Results can help us identify a new diagnostic system that can be used to diagnose MD.

Background The diagnosis of the rare genetic diseases has great importance in treating multisystemic conditions, preventing potential complications, and estimating disease risk for family members. The duration of obtaining genetic test results is varies. The demand to learn the diagnosis of a possible untreatable illness involves a struggle between uncertainty and a lifetime chronic disease. The current uncertainty of their child's condition and the long wait for a diagnosis may increase the parents' anxiety level and cause difficulties in the continuation of diagnostic procedures in some families. This study aimed to investigate the prediagnosis and postdiagnosis anxiety levels of parents who have a child with a rare genetic disease. Method The parents in this study, mothers or fathers, admitted their children to the Bezmialem Vakıf University Medical Genetics Clinic due to a suspected rare genetic disease (n = 40). Researchers created “The Sociodemographic Questionnaire” and used it to analyze the parents' sociodemographic status. In addition, they used the State-Trait Anxiety Inventory (STAI) to determine the anxiety levels of the parents. Results The state anxiety levels of parents decreased significantly after learning the diagnosis. However, there was no statistically significant decrease observed in trait anxiety levels. Conclusion Data from this study revealed that informing parents about their child's disease and properly explaining to them the expected difficulties might help to reduce their anxiety levels. Psychological support for parents is necessary to reduce their long-term stress, thus increasing the patient's compliance with treatment.

Highlights • COVID-19 has neuro-invasion potential independently of the critical disease process. • Cerebrovascular diseases such as ischemia may develop in the course of disease. • Increased inflammation may be predicted by CRP and D-dimer levels. • The elder Covid-19 patients with prothrombotic risk factors should also be considered for the signs of stroke., Coronaviruses are revealed to target the human respiratory system mainly. However, they also have neuro-invasive abilities and might spread from the respiratory system to the central nervous system. Herein, we report four patients with COVID-19 simultaneously diagnosed with acute ischemic stroke. There were four stroke cases with simultaneously diagnosis of Covid-19 till the April 14, 2020 in the city of Sakarya, Turkey. They were aged between 45 to 77 years. All four cases were likely to have contracted the virus in Sakarya. The patients had all commonly reported symptoms of Covid-19. Three patients have elevated D-dimer levels, and two of them had high C-reactive protein (CRP) levels. They were managed symptomatically for both the infection and the stroke. Our findings suggest that ischemic cerebrovascular diseases may simultaneously develop in the course of Covid-19 independently of the critical disease process. Increased inflammation predicted by CRP and D-dimer levels may play a role in the formation of ischemia. In particular, elder patients with prothrombotic risk factors should also be considered for the signs of cerebrovascular events in addition to infectious symptoms.

Clinical and experimental studies show that epilepsy affects cardiac function; however, the underlying molecular mechanism has not been fully elucidated. Inwardly-rectifying potassium (Kir) channels transport K+ ions into excitable cells such as neurons and cardiomyocytes; they control the cell excitability by acting towards the repolarization phase of cardiac action potential. Kir channel expression has been previously shown to vary in epileptic brains, at the same time seizures are known to affect the autonomic nervous system. Kir channel expression in cardiac tissue is a possible mechanism for the explanation of cardiac pathology in epilepsy. We investigate the expression of Kir channels in epileptic cardiac tissue by using pentylenetetrazole (PTZ)-kindling model in rats. Our molecular analyses showed significant decrease in cardiac Kir channel mRNA and protein expression of PTZ-kindled rats. Interestingly, both Kir2.x, which directs IK1 flux in ventricular tissue and Kir3.x, which is responsible for IKACh in the atria, were observed to decrease significantly. Kir channel expression also differs between females and males. This is the first study to our knowledge in epileptic cardiac tissue showing the expression of Kir channels. Our results show that Kir channels may play a role in cardiac pathology associated with epilepsy.

Epilepsy is a result of unprovoked, uncontrollable, and repetitive outburst of abnormal and excessive electrical discharges, known as seizures, in the neurons. Epilepsy is a devastating neurological condition that affects 70 million people globally. Unfortunately, only two-thirds of epilepsy patients respond to antiepileptic drugs while others become drug resistant and may be more prone to epilepsy comorbidities such as SUDEP. Oxidative stress, mitochondrial dysfunction, imbalance in the excitatory and inhibitory neurotransmitters, and neuroinflammation are some of the common pathologies of neurological disorders and epilepsy. Studies suggests that melatonin, a pineal hormone that governs sleep-wake cycles, may be neuroprotective against neurological disorders and thus may be translated as an antiepileptic as well. Melatonin has been shown to be an antioxidant, antiexcitotoxic, and anti-inflammatory hormone/molecule in neurodegenerative diseases, which may contribute to its antiepileptic and neuroprotective properties in epilepsy as well. In addition, melatonin has evidently been shown to play a regulatory role in the cardiorespiratory system and sleep-wake cycles, which may have positive implications toward epilepsy associated comorbidities, such as SUDEP. However, studies investigating the changes in melatonin release due to epilepsy and melatonin's antiepileptic role have been inconclusive and scarce, respectively. Thus, this comprehensive review aims to summarize and elucidate the potential role of melatonin in the pathogenesis of epilepsy and its comorbidities, in hopes to develop new diagnostic and therapeutic approaches that will improve the lives of epileptic patients, particularly those who are drug resistant.

Over the decades, various interventions have been developed and utilized to treat epilepsy. However, the majority of epileptic patients are often first prescribed anti-epileptic drugs (AED), now known as anti-seizure drugs (ASD), as the first line of defense to suppress their seizures and regain their quality of life. ASDs exert their anti-convulsant effects through various mechanisms of action, including regulation of ion channels, blocking glutamate-mediated stimulating neurotransmitter interaction, and enhancing the inhibitory GABA transmission. About one-third of epileptic patients are often resistant to anti-convulsant drugs, while others develop numerous side effects, which may lead to treatment discontinuation and further deterioration of quality of life. Common side effects of ASDs include headache, nausea and dizziness. However, more adverse effects, such as auditory and visual problems, skin problems, liver dysfunction, pancreatitis and kidney disorders may also be witnessed. Some ASDs may even result in life-threatening conditions as well as serious abnormalities, especially in patients with comorbidities and in pregnant women. Nevertheless, some clinicians had observed a reduction in the development of side effects post individualized ASD treatment. This suggests that a careful and well-informed ASD recommendation to patients may be crucial for an effective and side-effect-free control of their seizures. Therefore, this review aimed to elucidate the anticonvulsant effects of ASDs as well as their side effect profile by discussing their mechanism of action and reported adverse effects based on clinical and preclinical studies, thereby providing clinicians with a greater understanding of the safety of current ASDs.

Epilepsy is a neurologicaldisorder characterized by persistent predisposition to recurrent seizurescaused by abnormal neuronal activity in the brain. Epileptic seizures maydevelop due to a relative imbalance of excitatory and inhibitory neurotransmitters. Expressional alterations of receptors and ion channelsactivated by neurotransmitters can lead to epilepsy pathogenesis. Aims In this updated comprehensive review, we discuss the emerging implication of mutations in neurotransmitter-mediated receptors and ion channels. We aim to provide critical findings of the current literature about the role of neurotransmitters in epilepsy. Materials and methods A comprehensive literature review was conducted to identify and critically evaluate studies analyzing the possible relationship between epilepsy and neurotransmitters. The PubMed database was searched for related research articles. Key findings Glutamate and gamma-aminobutyric acid (GABA) are the main neurotransmitters playing a critical role in the pathophysiology of this balance, and irreversible neuronal damage may occur as a result of abnormal changes in these molecules. Acetylcholine (ACh), the main stimulant of the autonomic nervous system, mediates signal transmission through cholinergic and nicotinic receptors. Accumulating evidence indicates that dysfunction of nicotinic ACh receptors, which are widely expressed in hippocampal and cortical neurons, may be significantly implicated in the pathogenesis of epilepsy. The dopamine-norepinephrine-epinephrine cycle activates hormonal and neuronal pathways; serotonin, norepinephrine, histamine, and melatonin can act as both hormones and neurotransmitters. Recent reports have demonstrated that nitric oxide mediates cognitive and memory-related functions via stimulating neuronal transmission. Significance The elucidation of the role of the main mediators and receptors in epilepsy is crucial for developing new diagnostic and therapeutic approaches.

WOS:000558679700028 PubMed: 33040832 Skeletal system and some organs development changes in rat fetuses with 30 and 60 mg/kg caffeine and melatonin's (10 mg/kg) protective role against rat fetuses were investigated. Groups (n = 4) were formed as Control, LDC, HDC, LDC+melatonin, HDC+melatonin and melatonin. Fetuses were taken by cesarean section and stained using dual skeletal staining method and FESEM. TRAP and AP immune-reactivity concentrations were calculated. Oxidative stress and inflammatory markers were also measured by liver, bone and placenta samples. TNT-alpha, IL-1 beta, IL-6, VEGF-A, SOST and Fetuin-A levels were measured in tissue by using ELISA. TBARS, SOD, GSH, GSSG, TOS, TAS, measured by spectrophotometric assay method. The mRNA levels of Agtr2 gene expressed in placental tissues of control rats and in placental tissues of rats exposed to HDC, LDC, MEL, HDC+MEL, LDC+MEL were analyzed by Real-time PCR. The gene expressions of Agtr2 were significantly upregulated in the placentas exposed to HDC. MEL. HDC+MEL and LDC+MEL (P0,05). According to these data, caffeine used during pregnancy delayed ossification; melatonin, a powerful antioxidant, was found to eliminate this effect. Besides, changes in angiotensin receptor expression observed in response to a caffeine and melatonin exposure result from high dose and join effect. Yozgat Bozok University Project Coordination Application and Research Center [6602c-TF/18-144] I would like to express my gratitude to Yozgat Bozok University Project Coordination Application and Research Center for supporting this project with BAP project number 6602c-TF/18-144.

Background: Sepsis is a serious clinical condition characterized by damage to the immune system as a result of an uncontrolled response to infection. Septic patients show complications such as fever, cardiovascular shock, and/or systemic organ failure. Acute organ failure formed in sepsis mostly affects the respiratory and cardiovascular systems. In sepsis, responses including pro-inflammatory and anti-inflammatory processes in addition to the Toll-Like Receptor 4 (TLR4) signals leading to the release of inflammatory mediators have been suggested to be fundamental pathways in the pathophysiology of sepsis. Purpose: In this context, unregulated levels of sepsis-associated inflammatory mediators may increase the risk of mortality. In sepsis, infection-induced pathogens lead to a systemic inflammatory response. These systemic responses may contribute to septic shock and organ dysfunction. In the unfavorable clinical course of sepsis, an uncontrolled inflammatory response is observed. Accordingly, the mechanism of inflammatory mediators such as cytokines and chemokines in sepsis might increase. Neurotransmitters and gene regulators affect inflammatory mediators and control the inflammatory response. In this review, we aimed to show the new therapeutic targets in sepsis treatment with current studies. New clinical implications targeting inflammatory mediators in high mortality affected by the uncontrolled inflammatory response in sepsis can contribute to the understanding of the symptoms.

In recent years, there is an increased research interest for plants which are natural sources of antioxidants. Lepidium sativum Subsp spinescens L., commonly found in South West Asia, is a plant known as a healthy nutritional source containing bio-molecules that carry anti-hypertensive, hypoglycemic, anti-asthmatic, antispasmodic, hepato-protective, chemoprotective, anti-inflammatory and anti-oxidant effects. In this study, we aimed to investigate the antioxidant content and activity of Lepidium sativum Subsp spinescens L. methanol extract on cancer cells. Methanol extract of dried Lepidium sativum Subsp spinescens L. was prepared. Total amount of phenolic compounds was determined by Slinkard and Singleton method using Folin-Ciocalteu reagent. Total flavonoid amount was determined according to Zhishen method. Antioxidant activity of the extract was evaluated by CUPRAC and ABTS radical scavenging activity assays. Cytotoxic effects of the plant extract on colon and endometrium cancer cells, and human peripheral lymphocyte cells were investigated in vitro by MTT and neutral red assays. Furthermore, the plant extract was investigated for necrotic effects by LDH assay; apoptotic activity by DNA ladder fragmentation, ELISA and acridine orange/ethidium bromide staining; and genotoxic effect by comet assay methods. Methanol extract of Lepidium sativum Subsp spinescens L. was found to have a high content of phenolic and flavonoid compounds. The extract showed significant antioxidant activity and also cytotoxic activity on colon and endometrium cancer cells in a concentration-dependent manner. Apoptotic activity and genotoxic effects were significantly increased, especially with 200 μg/ml concentrations at 48 hours incubation. In conclusion, it was determined that the extract evaluated in this study could be a natural source of antioxidants. Further molecular studies explaining chemo-preventive and chemotherapeutic effects on cancer cells are required to support anticancer efficacy of the plant.

Aim Diabetes mellitus (DM) is characterized by insulin resistance or hyperglycemia caused by insufficient insulin secretion. Acetylcholine (ACh) can stimulate insulin release depending on glucose while hyperglycemia in DM pathology can cause cellular hypoxia. Adaptive responses to hypoxia in DM are associated with stimulation of hypoxia-inducible factor 1-alpha (HIF-1α) signal due to hyperglycemia. Hypoxia affects potassium (K+) concentration by increasing excitability in K+ ion channels. In our study, we aimed to evaluate the immunoexpression of adaptive responses to hypoxia that develops with DM in pancreatic and cardiac tissues. Materials and methods In this study, 14 Balb/C female mice were divided into control and type 1 DM groups. Streptozotocin (STZ; 150 mg/kg/bw) was injected intraperitoneally in mice to create a type 1 diabetes model. During the experiment, diabetic mice with a daily blood-glucose value higher than 250 mg/dl were injected subcutaneously with 1 U/day insulin. Two weeks after STZ injection, the mice were euthanized by cervical dislocation and the heart and pancreatic tissues were removed and prepared for histological and immunohistochemical analysis for TNF-α, HIF-1α, Kir6.2, Kir3.1, and M2 muscarinic receptor. Key findings Significant increase of TNF-α, HIF-1α, and Kir6.2 immunoreactivity was observed in both cardiac and pancreatic tissues of type 1 DM mice. And also, cardiac Kir3.1 and M2 muscarinic receptor and pancreatic M2 muscarinic receptor immunoreactivities significantly increased. Significance Our study can contribute to understanding the role of Kir3.1, Kir6.2 channels, and hypoxia biomarkers in the type 1 DM mechanism.

Background: The KCNMA1 gene encodes the α-subunit of the large conductance, voltage, and calcium-sensitive potassium channel (BK channels) that plays a critical role in neuronal excitability. Heterozygous mutations in KCNMA1 were first illustrated in a large family with generalized epilepsy and paroxysmal nonkinesigenic dyskinesia. Recent research has established homozygous KCNMA1 mutations accountable for the phenotype of cerebellar atrophy, developmental delay, and seizures. Case report: Here, we report the case of a patient with a novel homozygous truncating mutation in KCNMA1 (p.Arg458Ter) presenting with both the loss- and gain-of-function phenotype with paroxysmal dyskinesia, epilepsy, intellectual delay, and corticospinal–cerebellar tract atrophy. Conclusion: This report extends the KNCMA1 mutation phenotype with a patient who carries a novel frameshift variant, presenting with both the gain- and loss-of-function phenotypes along with spinal tract involvement as a novel characteristic.