Seizure progression is slowed by enhancing neurosteroid availability in the brain of epileptic rats.

Trilostane is a 3ß-hydroxysteroid dehydrogenase/Δ5-4 isomerase inhibitor able to produce a manyfold increase in brain levels of various neurosteroids, including allopregnanolone. We previously found that treatment with trilostane can slow down epileptogenesis in the kainic acid (KA) model of temporal lobe epilepsy. It is unknown whether trilostane may have a similar effect on the progression of epilepsy severity, as observed in KA-treated rats. Consequently, we investigated the effects of trilostane (50 mg/kg/day, 1 week) in epileptic rats, given 64 days after KA administration. Seizures were monitored by video-electrocorticographic recordings before and during the treatment with trilostane or vehicle (sesame oil), and neurosteroid levels were measured in serum and cerebral tissue using liquid chromatography-electrospray tandem mass spectrometry after treatment. Pregnenolone sulfate, pregnenolone, progesterone, 5α-dihydroprogesterone, and allopregnanolone peripheral levels were massively increased by trilostane. With the only exception of hippocampal pregnenolone sulfate, the other neurosteroids augmented in both the neocortex and hippocampus. Only pregnanolone levels were not upregulated by trilostane. As expected, a significant increase in the seizure occurrence was observed in rats receiving the vehicle, but not in the trilostane group. This suggests that the increased availability of neurosteroids produced a disease-modifying effect in the brain of epileptic rats.

Pituitary apoplexy: a systematic review of non-gestational risk factors.

PURPOSE: Pregnancy is a known risk factor for Pituitary Apoplexy (PA) but there is a lack of consistency in the literature regarding non-gestational risk factors responsible for PA. METHODS: We did a systematic review following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify the non-gestational risk factors associated with the development of PA in adult patients with pituitary adenoma. Also, we discuss here a case of an elderly female with pituitary macroadenoma who was initially planned for pituitary resection electively but underwent emergency surgery after she developed PA. RESULTS: As per screening and eligibility criteria, seven studies with 4937 study participants were included in this systematic review out of which 490 (9.92%) patients had PA, including asymptomatic subclinical PA (SPA) and symptomatic clinical PA (CPA). The macroadenomas and negative staining of the tumor were found to be a significant risk factor consistently in multivariate analysis in three and two retrospective studies, respectively. However, the results were varied for any significant difference in the risk factors for apoplexy between SPA and CPA. Similarly, there was no consistency among the studies for risk factors significantly responsible for CPA or PA compared to controls. CONCLUSION: No single non-gestational risk factor is solely responsible for the development of PA in a pituitary adenoma compared to the control population. Tumor size (macroadenoma) and the non-functioning status of the adenoma are the only significant factors contributing independently toward an apoplectic event in most patients. Such patients can be prioritized for early pituitary tumor resection.

Single-Molecule Analysis of SARS-CoV-2 Binding to C-Type Lectin Receptors.

Despite intense scrutiny throughout the pandemic, development of efficacious drugs against SARS-CoV-2 spread remains hindered. Understanding the underlying mechanisms of viral infection is fundamental for developing novel treatments. While angiotensin converting enzyme 2 (ACE2) is accepted as the key entry receptor of the virus, other infection mechanisms exist. Dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) and its counterpart DC-SIGN-related (DC-SIGNR, also known as L-SIGN) have been recognized as possessing functional roles in COVID-19 disease and binding to SARS-CoV-2 has been demonstrated previously with ensemble and qualitative techniques. Here we examine the thermodynamic and kinetic parameters of the ligand-receptor interaction between these C-type lectins and the SARS-CoV-2 S1 protein using force-distance curve-based AFM and biolayer interferometry. We evidence that the S1 receptor binding domain is likely involved in this bond formation. Further, we employed deglycosidases and examined a nonglycosylated S1 variant to confirm the significance of glycosylation in this interaction. We demonstrate that the high affinity interactions observed occur through a mechanism distinct from that of ACE2.

Antiepileptogenic effects of trilostane in the kainic acid model of temporal lobe epilepsy.

OBJECTIVE: Epileptogenesis after status epilepticus (SE) has a faster onset in rats treated to reduce brain levels of the anticonvulsant neurosteroid allopregnanolone with the 5α-reductase inhibitor finasteride; however, it still has to be evaluated whether treatments aimed at increasing allopregnanolone levels could result in the opposite effect of delaying epileptogenesis. This possibility could be tested using the peripherally active inhibitor of 3ß-hydroxysteroid dehydrogenase/Δ5-4 isomerase trilostane, which has been shown repeatedly to increase allopregnanolone levels in the brain. METHODS: Trilostane (50 mg/kg) was administered subcutaneously once daily for up to six consecutive days, starting 10 min after intraperitoneal administration of kainic acid (15 mg/kg). Seizures were evaluated by video-electrocorticographic recordings for 70 days maximum, and endogenous neurosteroid levels were assessed by liquid chromatography-electrospray tandem mass spectrometry. Immunohistochemical staining was performed to evaluate the presence of brain lesions. RESULTS: Trilostane did not alter the latency of kainic acid-induced SE onset or its overall duration. When compared to the vehicle-treated group, rats receiving six daily trilostane injections presented a remarkable delay of the first spontaneous electrocorticographic seizure and subsequent tonic-clonic spontaneous recurrent seizures (SRSs). Conversely, rats treated with only the first trilostane injection during SE did not differ from vehicle-treated rats in developing the SRSs. Notably, trilostane did not modify neuronal cell densities or the overall damage in the hippocampus. In comparison to the vehicle group, repeated administration of trilostane significantly decreased the activated microglia morphology in the subiculum. As expected, allopregnanolone and other neurosteroid levels were remarkably increased in the hippocampus and neocortex of rats treated for 6 days with trilostane, but pregnanolone was barely detectable. Neurosteroids returned to basal levels after a week of trilostane washout. SIGNIFICANCE: Overall, these results suggest that trilostane led to a remarkable increase in allopregnanolone brain levels, which was associated with protracted effects on epileptogenesis.

The role of probiotic supplementation in inflammatory biomarkers in adults: an umbrella meta-analysis of randomized controlled trials.

OBJECTIVE: Despite the increasing evidence for probiotics' anti-inflammatory effects, the results of meta-analyses remain inconsistent. The present umbrella meta-analysis aimed to investigate the effects of probiotic supplementation on inflammatory biomarkers. METHODS: We performed a wide-ranging systematic search in several databases, including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar up to April 2023. The overall effect sizes were calculated using effect size (ES) values and their corresponding confidence intervals (CI). RESULTS: Out of a total of 580 related articles, 39 studies were qualified for inclusion in the analysis. The results of the analysis revealed a significant reduction of C-reactive protein (CRP) (ES = -1.02; 95% CI: -1.23, -0.80, p < 0.001; I2: 94.1%, p < 0.001), TNF-α (ES = -0.35; 95% CI: -0.50, -0.20, p < 0.001; I2: 75.6%, p < 0.001), and interleukin-6 (IL-6) levels (ES = -0.36; 95% CI: -0.59, -0.13, p = 0.002; I2: 85.6%, p < 0.001), following probiotic supplementation. CONCLUSION: Probiotic supplementation significantly reduced serum concentrations of TNF-a, CRP, and IL-6. Thus, probiotic supplementation can be considered adjuvant therapy to alleviate inflammation in various inflammatory conditions.

Protective effect of raisin (currant) against spatial memory impairment and oxidative stress in Alzheimer disease model.

Objectives: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive pathological changes of the brain. A number of studies demonstrated compelling evidence of the importance of oxidative processes in AD pathogenesis. Raisin contains polyphenol, phenolic acid, and tannin compounds, which have antioxidant and anti-inflammatory properties. The present study was aimed to evaluate the protective effect of raisin on neurobehavioral and histological changes in rats with Alzheimer. Methods: Animal model of AD was induced by intraperitoneal injection of aluminium chloride for 60 days (100 mg/kg body weight). During these 60 days both Alzheimer's and control rats were given 6 g of raisin per rat. At the end of the treatment, blood was collected for biochemical assessment. We used a Morris water task and passive avoidance test to assess spatial memory. Results: Our results showed that aluminium exposure significantly decreased the memory in the MWT and passive avoidance test, but in the raisin + AlCl3 group, it significantly increased spatial memory in both tests. Also, Aluminium exposure significantly increased malondialdehyde (MDA) and decreased ferric reducing ability of plasma (ferric reducing/antioxidant power (FRAP)), while treatment with raisin significantly decreased MDA and increased FRAP in plasma of blood. Discussion: Our findings showed that raisin has a neuroprotective effect and improves the spatial memory in AD animal models.

miR-302/367-induced neurons reduce behavioral impairment in an experimental model of Alzheimer's disease.

In vivo reprogramming of reactive glial cells to neurons has opened a new horizon in regenerative medicine. Our previous study showed that astrocytes could be converted to neurons by the microRNA-302/367 (miR-302/367) cluster in adult brains. In this study, we investigated the possible contribution of miR-302/367-induced neurons in behavioral improvement and neural repair in an Alzheimer's disease (AD) animal model. The AD model was induced by an intracerebroventricular (i.c.v) injection of streptozotocin (STZ). GFP-only or miR-302/367+GFP expressing lentiviral particles were injected into the dentate gyrus of the hippocampus along with intraperitoneal (i.p) valproate (VPA) injection, 3weeks after the STZ administration. We assessed short-term and spatial memories by the Y-maze and Morris water maze (MWM) tasks, respectively. Electrophysiological activities of induced neuron-like cells were investigated using a whole-cell patch clamp technique, 6months after injection of miR-302/367. Behavioral analysis showed that the STZ injection significantly impaired short-term memory and increased escape latency parameter in the MWM task. Compared to STZ and STZ+VPA groups, miR-302/367 combined with VPA significantly improved the spontaneous alternation and spatial memory. Immunostaining against NeuN, as a mature neuronal marker, and its quantification indicated that co-labeled GFP and NeuN significantly increased in the miR-302/367+VPA group. Induced neurons were detected 6months after the miR-302/367 injection. The patch-clamp recording suggested that induced neurons could fire repetitive action potential like endogenous neurons. In conclusion, our results indicated that in vivo reprogramming of reactive astrocytes to neurons by the miR-302/367 cluster might be considered as a novel strategy to restore learning and memory in AD patients.

Arbutin reduces cognitive deficit and oxidative stress in animal model of Alzheimer's disease.

Objectives: Recent evidences have shown the beneficial effects of natural products for treating of Alzheimer's disease (AD). Arbutin is derived from Pyrus biossieriana and exerts a wide range of pharmacological activities including anti-inflammatory and anti-oxidant effects. The present study was designed to examine the protective effects of arbutin on streptozotocin (STZ)-induced neurotoxicity in rats. Materials and methods: The spatial memory impairment was induced by intracerebroventricular (i.c.v) microinjection of STZ (3 mg/kg, 10 µL). Animals received the pretreatment of arbutin (50 mg/kg) for 21 days before STZ injection. The Morris Water maze (MWM) task was used to study the spatial learning and memory. The levels of oxidative stress markers including malondialdehyde (MDA), nitrite and carbonyl were measured in serum and hippocampus samples. In addition, antioxidant level was assessed by ferric reducing antioxidant power (FRAP) test. Results: The obtained result indicated that administration of STZ is led to memory impairment and increases the levels of oxidative stress markers in the hippocampus tissues. Conversely, arbutin improves spatial memory and reduces oxidative and nitrosative stress, as evidenced by a significant decrease in the amount of MDA and nitrite in the serum and hippocampus. In addition, an increase in FRAP levels of hippocampus was observed in arbutin receiving animals. The protein carbonyl content was not reduced in arbutin receiving animals. Conclusion: It could be concluded that arbutin protects the brain against STZ-induced memory impairment and oxidative damage in the hippocampus. The neuroprotective effect of arbutin might be mediated through its antioxidant and free radical scavenging effects.

Anticipatory effect of execution on observation: an approach using ExoPinch finger robot

Background/aim: This study aims to explore the mirror neuron system (MNS) involvement using mu (8­12 Hz)/beta (15­25 Hz) band suppression in an action observation-execution paradigm. Materials and methods: Electrophysiological (EEG) data from 16 electrodes were recorded while 8 participants observed video clips of a hand squeezing a spring. Specifically, the effect of anticipated execution on observation was studied. For this purpose, a fully actuated finger exoskeleton robot was utilized to synchronize observation and execution and to control the execution condition for the partici-pants. Anticipatory effect was created with a randomized robot accompany session. Results: The results showed that the observational condition (with or without anticipation) interacted with hemisphere at central chan-nels near somatosensory cortex. Additionally, we explored the response of MNS on the kinetics features of visual stimuli (hard or soft spring). Conclusion: he results showed an interaction effect of kinetics features and hemisphere at frontal channels corresponding nearly to the ventral premotor cortex area of the brain. The activation of mirror neurons in this area plays a crucial role in observational learning. Based on our results, we propose that specific type of visual stimuli can be combined with the functional abilities of the MNS in the ac-tion observation based treatment of hand motor dysfunction of stroke patients to have a positive additional impact.

Enhancing recovery of recombinant hepatitis B surface antigen in lab-scale and large-scale anion-exchange chromatography by optimizing the conductivity of buffers.

In biopharmaceutical science, ion-exchange chromatography (IEC) is a well-known purification technique to separate the impurities such as host cell proteins from recombinant proteins. However, IEC is one of the limiting steps in the purification process of recombinant hepatitis B surface antigen (rHBsAg), due to its low recovery rate (<50%). In the current study, we hypothesized that ionic strengths of IEC buffers are easy-to-control parameters which can play a major role in optimizing the process and increasing the recovery. Thus, we investigated the effects of ionic strengths of buffers on rHBsAg recovery via adjusting Tris-HCl and NaCl concentrations. Increasing the conductivity of equilibration (Eq.), washing (Wash.) and elution (Elut.) buffers from their initial values of 1.6 mS/cm, 1.6 mS/cm, and 7.0 mS/cm to 1.6 mS/cm, 7 mS/cm and 50 mS/cm, respectively yielded an average recovery rate of 82% in both lab-scale and large-scale weak anion-exchange chromatography without any harsh effect on the purity percentage of rHBsAg. The recovery enhancement via increasing the conductivity of Eq. and Wash. buffers can be explained by their roles in reducing the binding strength and aggregation of retained particles in the column. Moreover, further increase in the salt concentration of Elut. Buffer could substantially promote the ion exchange process and the elution of retained rHBsAg.

PBP-A, a cyanobacterial DD-peptidase with high specificity for amidated muropeptides, exhibits pH-dependent promiscuous activity harmful to Escherichia coli.

Penicillin binding proteins (PBPs) are involved in biosynthesis, remodeling and recycling of peptidoglycan (PG) in bacteria. PBP-A from Thermosynechococcus elongatus belongs to a cyanobacterial family of enzymes sharing close structural and phylogenetic proximity to class A ß-lactamases. With the long-term aim of converting PBP-A into a ß-lactamase by directed evolution, we simulated what may happen when an organism like Escherichia coli acquires such a new PBP and observed growth defect associated with the enzyme activity. To further explore the molecular origins of this harmful effect, we decided to characterize deeper the activity of PBP-A both in vitro and in vivo. We found that PBP-A is an enzyme endowed with DD-carboxypeptidase and DD-endopeptidase activities, featuring high specificity towards muropeptides amidated on the D-iso-glutamyl residue. We also show that a low promiscuous activity on non-amidated peptidoglycan deteriorates E. coli's envelope, which is much higher under acidic conditions where substrate discrimination is mitigated. Besides expanding our knowledge of the biochemical activity of PBP-A, this work also highlights that promiscuity may depend on environmental conditions and how it may hinder rather than promote enzyme evolution in nature or in the laboratory.

Effect of Rosa damascena Extract on Rat Model Alzheimer's Disease: A Histopathological, Behavioral, Enzyme Activities, and Oxidative Stress Study.

The purpose of the current study is to investigate the effect of aquatic Rosa damascena extract against the oxidative damage induced by aluminum chloride intoxication in Alzheimer's model of Wister rats. Rats were divided randomly into seven groups (n = 10). Control group received no treatment, sham group received distilled water orally, aluminum group (AL) was administered AlCl3 (100 mg/kg) orally, extract 1 and 2 groups were treated with only aqueous R. damascena extract (DRE) (500 and 1000 mg/kg), and treatment 1 and 2 groups received aqueous R. damascena extract (500 and 1000 mg/kg) and AlCl3 (100 mg/kg) orally. The brain tissues were sampled for histopathological examination, and biochemical analysis was conducted for estimating the enzyme activities of acetylcholinesterase and catalase (CAT), the levels of GSH and MDA, and ferric reducing antioxidant power. According to the results of behavioral tests, AL administration showed a reduction in spatial memory and remarkably increased the time needed for reaching the invisible platform. The administration of Al-induced oxidative stress and an increase of the enzyme activity of AChE. Al administration increased AChE level from 1.176 ± 0.173 to 3.62 ± 0.348, which was a significant rise. However, treating with the extract at the dose of 1000 mg/kg downregulated it to 1.56 ± 0.303. Administration of the R. damascene extract caused an increased level of catalase and glutathione levels in treatment groups, attenuated MDA level, and regulated AChE activity. Our results illustrate that administration of R. damascene extract has a protective effect against the oxidative damage induced by AlCl3 intoxication in Alzheimer's model.

Effective Connectivity Estimation by a Hybrid Neural Network, Empirical Wavelet Transform, and Bayesian Optimization.

Accurately measuring nonlinear effective connectivity is a crucial step in investigating brain functions. Brain signals like EEG is nonstationary. Many effective connectivity methods have been proposed but they have drawbacks in their models such as a weakness in proposing a way for hyperparameter and time lag selection as well as dealing with non-stationarity of the time series. This paper proposes an effective connectivity model based on a hybrid neural network model which uses Empirical Wavelet Transform (EWT) and a long short-term memory network (LSTM). The best hyperparameters and time lag are selected using Bayesian Optimization (BO). Due to the importance of generalizability in neural networks and calculating GC, an algorithm was proposed to choose the best generalizable weights. The model was evaluated using simulated and real EEG data consisting of attention deficit hyperactivity disorder (ADHD) and healthy subjects. The proposed model's performance on simulated data was evaluated by comparing it with other neural networks, including LSTM, CNN-LSTM, GRU, RNN, and MLP, using a Blocked cross-validation approach. GC of the simulated data was compared with GRU, linear Granger causality (LGC), Kernel Granger Causality (KGC), Partial Directed Coherence (PDC), and Directed Transfer Function (DTF). Our results demonstrated that the proposed model was superior to the mentioned models. Another advantage of our model is robustness against noise. The results showed that the proposed model can identify the connections in noisy conditions. The comparison of the effective connectivity of ADHD and the healthy group showed that the results are in accordance with previous studies.

Application of mesenchymal stem cells (MSCs) in neurodegenerative disorders: History, findings, and prospective challenges.

Over the past few decades, the application of mesenchymal stem cells has captured the attention of researchers and practitioners worldwide. These cells can be obtained from practically every tissue in the body and are used to treat a broad variety of conditions, most notably neurological diseases such as Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, and Alzheimer's disease. Studies are still being conducted, and the results of these studies have led to the identification of several different molecular pathways involved in the neuroglial speciation process. These molecular systems are closely regulated and interconnected due to the coordinated efforts of many components that make up the machinery responsible for cell signaling. Within the scope of this study, we compared and contrasted the numerous mesenchymal cell sources and their cellular features. These many sources of mesenchymal cells included adipocyte cells, fetal umbilical cord tissue, and bone marrow. In addition, we investigated whether these cells can potentially treat and modify neurodegenerative illnesses.

Therapeutic Potential of Mesenchymal Stem Cells in the Treatment of Epilepsy and Their Interaction with Antiseizure Medications.

Epilepsy is a life-threatening neurological disease that affects approximately 70 million people worldwide. Although the vast majority of patients may be successfully managed with currently used antiseizure medication (ASM), the search for alternative therapies is still necessary due to pharmacoresistance in about 30% of patients with epilepsy. Here, we review the effects of ASMs on stem cell treatment when they could be, as expected, co-administered. Indeed, it has been reported that ASMs produce significant effects on the differentiation and determination of stem cell fate. In addition, we discuss more recent findings on mesenchymal stem cells (MSCs) in pre-clinical and clinical investigations. In this regard, their ability to differentiate into various cell types, reach damaged tissues and produce and release biologically active molecules with immunomodulatory/anti-inflammatory and regenerative properties make them a high-potential therapeutic tool to address neuroinflammation in different neurological disorders, including epilepsy. Overall, the characteristics of MSCs to be genetically engineered, in order to replace dysfunctional elements with the aim of restoring normal tissue functioning, suggested that these cells could be good candidates for the treatment of epilepsy refractory to ASMs. Further research is required to understand the potential of stem cell treatment in epileptic patients and its interaction with ASMs.

Autophagy Modulation and Cancer Combination Therapy: A Smart Approach in Cancer Therapy.

The autophagy pathway is the process whereby cells keep cellular homeostasis and respond to stress via recycling their damaged cellular proteins, organelles, and other cellular components. In the context of cancer, autophagy is a dual-edge sword pro- and anti-tumorigenic role depending on the oncogenic context and stage of tumorigenesis. Cancer cells have a higher dependency on autophagy compared with normal cells because of cellular damages and high demands for energy. The carbon, nitrogen, and molecular oxygen are building blocks for highly proliferative cancer cells which extremely depend on glutaminolysis and aerobic glycolysis; when a cancer cell is restricted to glucose and glutamine, it initiates to activate a stress response pathway using autophagy. Oncogenic tyrosine kinases (OncTKs) and receptor tyrosine kinases (RTKs) activation result in autophagy modulation through activation of the PI3K/AKT/mTORC1 and RAS/MAPK signaling pathways. Targeted inhibition of tyrosine kinases (TKs) and RTKs have recently been considered as cancer therapy but drug resistance and cancer relapse continue to be a major limitation of tyrosine kinase inhibitors (TKIs). Manipulation of autophagy pathway along with TKIs may be a promising strategy to circumvent unknown existing drug-resistance mechanisms that may emerge in a treated patient. In this way, clinical trials are ongoing to modulate autophagy to treat cancer. This review aims to summarize the combination therapy of autophagy affecting compounds with anticancer drugs which target cell signaling pathways, metabolism mechanisms, and epigenetics modification to improve therapeutic efficacy against cancers.

Evaluation of Thymic Output and Regulatory T Cells in Kidney Transplant Recipients with Chronic Antibody-Mediated Rejection.

BACKGROUND: Regulatory T cells (Tregs) and recent thymic emigrants (RTEs) have an essential role in the regulation of allogeneic immune responses. However, their mechanisms of action in chronic antibody-mediated rejection (cAMR) are still unclear. In this study, we aimed to compare Treg and RTE levels between stable graft function (SGF) patients and cAMR subjects after kidney transplantation. METHOD: Mononuclear cells (MNs) were separated from peripheral blood, and flow cytometry analysis was performed for detection of CD4+ and CD25high as Treg markers and CD4+, CD31+, and CD45RA+ as RTE immunophenotyping markers. RESULT: The level of peripheral Treg cells was significantly lower in cAMR subjects in comparison to stable graft function patients. Moreover, SGF patients who had received cyclosporine A had a higher level of Treg in comparison to the tacrolimus recipients. Nevertheless, the RTE level between SGF and cAMR patients did not show any significant differences. CONCLUSION: It seems that Treg cells are significantly associated with transplant outcomes in cAMR patients, and prescribed immunosuppressive drugs can influence the frequency of this crucial subset of T cells. Although these drugs are beneficial and inevitable for allograft maintenance, more investigations are needed to elucidate their complete effects on different immune cell subsets which some of them like Tregs are in favor of transplant tolerance. Besides, the thymic output is seemingly not a beneficial biomarker for predicting cAMR; however, more in vivo and in vitro studies are needed for revealing the precise role of Tregs and RTEs in the transplantation context.

Intravenous Immunoglobulin Therapy in Myocarditis.

Myocarditis is an inflammatory disease of the myocardium with lymphocyte infiltration and myocyte necrosis leading to a wide range of clinical presentations including heart failure, arrhythmia, and cardiogenic shock. Infectious and noninfectious agents may trigger the disease. The fact that immunosuppressive drugs are useful in several kinds of autoimmune myocarditis is proof of the autoimmune mechanisms involved in the development of myocarditis. Pathogenic mechanisms in myocardial inflammation are including inflammasome activation followed by myocyte destruction, myocarditis, and pericarditis. Intravenous immunoglobulin (IVIG) is a serum product made up of immunoglobulins, widely used in a variety of diseases. This product is effective in several immune-mediated pathologies. As well as the determined usage of IVIG in Kawasaki disease, IVIG may be useful in several kinds of heart failure including fulminant myocarditis, acute inflammatory cardiomyopathy, Giant Cell Myocarditis, and peripartum cardiomyopathy. Generally, IVIG is used in two different doses of low dose (200 to 400 mg/kg) and high dose (2 g/kg) regimen. The exact therapeutic effects of IVIG are not clear, however over the last decades, our knowledge about its mechanism of function has greatly enhanced. IVIG administration should be based on the accepted protocols of its transfusion. In this review article, we try to provide an overview of the different kinds of myocarditis, pathologic mechanisms and their common treatments and evaluation of the administration of IVIG in these diseases. Furthermore, we will review current protocols using IVIG in each disease individually.

Myristica Fragrans Houtt Extract Attenuates Neuronal Loss and Glial Activation in Pentylenetetrazol-Induced Kindling Model.

Inflammatory reactions are closely associated with the development and progression of epilepsy. It has been shown that inhibition of pro-inflammatory cytokines, which are released from activated astrocytes and microglia, are considered to be an effective therapeutic approach for the treatment of epileptic disorders. Regarding the anti-inflammatory effects of nutmeg (Myristica fragrans Houtt), the present study was designed to investigate whether the nutmeg ethanolic extract could exert anticonvulsant and inhibitory effects on glial activation in pentylenetetrazol (PTZ)-induced mice model of kindling. Ethanolic extract of nutmeg was administrated intraperitoneally (i.p.) 1 hour before PTZ injection or one week before PTZ as a separate group, to become fully-kindled. The chemical components of nutmeg extract were analyzed by gas chromatography mass spectrometry (GC-MS). Immunostaining against neuronal and glial markers was performed on hippocampus sections. GC-MS data indicated that the main components of nutmeg extract are myristic acid (39.93%), elemicin (22.16%) and myristicin (11.17%). Behavioral studies showed that pre-treatment of nutmeg extract effectively reduced seizures behavior, decreased cell death, and ameliorated glial activation that is followed by PTZ administration. In conclusion, nutmeg extract might be regarded as a useful supplementary agent in epilepsy treatment through its attenuation of neuronal loss and glial activation.

Inhibition of GABA A receptor improved spatial memory impairment in the local model of demyelination in rat hippocampus.

Cognitive impairment and memory deficit are common features in multiple Sclerosis patients. The mechanism of memory impairment in MS is unknown, but neuroimaging studies suggest that hippocampal demyelination is involved. Here, we investigate the role of GABA A receptor on spatial memory in the local model of hippocampal demyelination. Demyelination was induced in male Wistar rats by bilaterally injection of lysophosphatidylcholine (LPC) 1% into the CA1 region of the hippocampus. The treatment groups were received daily intraventricular injection of bicuculline (0.025, 0.05µg/2µl/animal) or muscimol (0.1, 0.2µg/2µl/animal) 5days after LPC injection. Morris Water Maze was used to evaluate learning and memory in rats. We used Luxol fast blue staining and qPCR to assess demyelination extention and MBP expression level respectively. Immunohistochemistry (IHC) for CD45 and H&E staining were performed to assess inflammatory cells infiltration. Behavioral study revealed that LPC injection in the hippocampus impaired learning and memory function. Animals treated with both doses of bicuculline improved spatial learning and memory function; however, muscimol treatment had no effect. Histological and MBP expression studies confirmed that demylination in LPC group was maximal. Bicuculline treatment significantly reduced demyelination extension and increased the level of MBP expression. H&E and IHC results showed that bicuculline reduced inflammatory cell infiltration in the lesion site. Bicuculline improved learning and memory and decreased demyelination extention in the LPC-induced hippocampal demyelination model. We conclude that disruption of GABAergic homeostasis in hippocampal demyelination context may be involved in memory impairment with the implications for both pathophysiology and therapy.