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Objective(s): Despite the many benefits of mesenchymal stem cell (MSC) transplantation for tissue regeneration, there are some limitations to using them, including the high costs, applying invasive procedures, the possibility of transplant rejection, and cell malignancy. This study aimed to investigate the effect of secretions of bone marrow stromal cells (BMSCs) with the cell-free strategy on damaged sciatic nerve with an emphasis on the role of apoptosis and the expression of myelin protein zero (MPZ) and nerve growth factor (NGF) proteins. Materials and Methods: BMSCs were cultured and a 25-fold concentrated conditioned medium (CM) from the cells was provided. After creating a crush injury in the left sciatic nerve of male rats, BMSCs or CM were injected into the injured site of the nerve. Four weeks later, the expression of MPZ, NGF, Bax, and Bcl-2 proteins in the sciatic nerve and histological parameters of the sciatic nerve and gastrocnemius muscle were assessed. Results: The results demonstrated that injection of CM decreased apoptosis and increased expression of MPZ and NGF proteins, improving remyelination and regeneration of the sciatic nerve almost as much as the transplantation of the BMSCs themselves compared to the control group. Conclusion: The results suggest that BMSC secretions may improve remyelination and regeneration of damaged sciatic nerve by increasing the expression of MPZ and NGF and decreasing apoptosis. [ABSTRACT FROM AUTHOR]

Aim: Low frequency stimulation (LFS) inhibits neuronal hyperexcitability following epileptic activity. However, knowledge about LFS' inhibitory mechanisms is lacking. Here, α1 and α2 adrenergic receptors' roles in mediating LFS inhibitory action on high-K+ induced epileptiform activity (EA) was examined in rat hippocampal slices. Materials and methods: LFS (1 Hz, 900 pulses) was applied to the Schaffer collaterals. Whole-cell, patch clamp recording was used to measure changes in CA1 pyramidal neurons' excitability. By applying high-K+ on hippocampal slices, EA was induced, and neuronal excitability increased. Results: When administered at the beginning of EA, LFS reduced neuronal excitability. In the presence of prazosin (10 µM, an α1 adrenergic receptor antagonist) and yohimbine (5 µM, an α2 adrenergic receptor antagonist), LFS' typically has a restorative impact on EA-induced membrane potential hyperpolarization and spike firing frequency, but this effect was reduced after high-K+ washout; These antagonists did not have a significant effect on LFS' inhibitory action on spike firing during EA. Conclusion: These findings suggest that LFS' anticonvulsant effect, on neuronal hyperexcitability following high-K+ EA, may be mediated partly through α adrenergic receptors in hippocampal slices. [ABSTRACT FROM AUTHOR]

Epilepsy is a prevalent neurological disorder characterized by recurrent seizures, which arise from the abnormal excessive or synchronous neuronal activity in the brain. Understanding the complex pathobiology of epilepsy is crucial for developing more effective diagnostic tools and targeted therapeutic interventions. This comprehensive review examines the current understanding of the molecular, cellular, and genetic mechanisms underlying the epileptic condition. The key pathological mechanisms discussed include neuronal hyperexcitability, imbalances in excitatory and inhibitory neurotransmitter systems, structural and functional changes in the brain, altered ion channel function and ion homeostasis, neuroinflammation, and the influence of genetic factors and epigenetic modifications. Delving into the molecular and cellular underpinnings, the review explores the impact of genetic mutations on ion channels and neurotransmitter receptors, the dysregulation of gene expression and epigenetic alterations, mitochondrial dysfunction and oxidative stress, as well as the role of synaptic plasticity and network reorganization in the pathogenesis of epilepsy. The clinical implications of these pathobiological insights are also discussed, highlighting the potential for novel biomarkers, diagnostic approaches, and targeted therapeutic strategies. The review underscores the importance of personalized medicine and precision treatment, as the heterogeneity of epilepsy necessitates tailored management strategies based on individual patient characteristics. Finally, the article explores ongoing research and future directions in the field, including the identification of novel therapeutic targets and the emergence of innovative technologies to better understand and manage this complex neurological disorder. [ABSTRACT FROM AUTHOR]

A patient with epilepsy was shown to have neurobiological, psychological, cognitive, and social issues as a result of recurring seizures, which is regarded as a chronic brain disease. However, despite numerous drug treatments, approximately, 30%-40% of all patients are resistant to antiepileptic drugs. Therefore, newer therapeutic modalities are introduced into clinical practice which involve neurostimulation and direct stimulation of the brain. Hence, we review published literature on vagus nerve stimulation, trigeminal nerve stimulation, applying responsive stimulation systems, and deep brain stimulation (DBS) in animals and epileptic patient with an emphasis on drug-resistant epilepsy. [ABSTRACT FROM AUTHOR]

The small nucleolar RNA host genes (SNHGs) belong to the long non-coding RNAs and are reported to be able to influence all three levels of cellular information-bearing molecules, that is, DNA, RNA, and proteins, resulting in the generation of complex phenomena. As the host genes of the small nucleolar RNAs (snoRNAs), they are commonly localized in the nucleolus, where they exert multiple regulatory functions orchestrating cellular homeostasis and differentiation as well as metastasis and chemoresistance. Indeed, worldwide literature has reported their involvement in the epithelial–mesenchymal transition (EMT) of different histotypes of cancer, being able to exploit peculiar features, for example, the possibility to act both in the nucleus and the cytoplasm. Moreover, SNHGs regulation is a fundamental topic to better understand their role in tumor progression albeit such mechanism is still debated. Here, we reviewed the biological functions of SNHGs in particular in the EMT process and discussed the perspectives for new cancer therapies. [ABSTRACT FROM AUTHOR]

Background: Borderline personality disorder (BPD) has been considered a psychiatric disorder, the effective pharmacological treatments for which have not been well established. Objectives: This study aimed to assess the efficacy of memantine (10 mg/day) in reducing BPD severity and cognitive impairment. Methods: The BPD patients diagnosed by psychologists were included and divided into the placebo (n = 19) and memantine (n = 20) groups. Included participants were randomized, double-blinded, and stabilized on the medication and psychotherapy for at least four weeks. The patients in the memantine group received oral memantine (10 mg/day) for four weeks. The severity of BPD was assessed by a self-reported questionnaire named Borderline Evaluation of Severity Over Time (BEST). Moreover, the Wisconsin test was carried out to assess executive function. Results: The mean score of the BEST test significantly decreased in week eight post-treatment in the memantine group. In addition, a significant decrease in this score was indicated in the memantine group compared to the placebo group in week eight. The mean total score of the BEST test was not significantly different before and after the placebo administration. There was no significant difference in the Wisconsin subscales, including the number of wrong answers and categories achieved after memantine or placebo administration. Perseverative errors rose after the administration of memantine. Adverse side effects did not occur in any of the participants. Conclusions: Our findings suggested the potential therapeutic effects of memantine for BPD. Furthermore, we found that a low dose of meantime might be preferable to prevent the side effects. [ABSTRACT FROM AUTHOR]

Background: Neurostimulation is one of the new therapeutic approaches in patients with drug-resistant epilepsy, and despite its high efficiency, its mechanism of action is still unclear. On the one hand, electrical stimulation in the human brain is immoral; on the other hand, the creation of the epilepsy model in laboratory animals affects the entire brain network. As a result, one of the ways to achieve the neurostimulation mechanism is to use epileptiform activity models In vitro. In vitro models, by accessing the local network from the whole brain, we can understand the mechanisms of action of neurostimulation., Methods: A literature search using scientific databases including PubMed, Google Scholar, and Scopus, using "Neurostimulation" and "epileptiform activity" combined with "high-frequency stimulation", " low-frequency stimulation ", and "brain slices" as keywords were conducted, related concepts to the topic gathered and are used in this paper., Results: Electrical stimulation causes neuronal depolarization and the release of GABAA, which inhibits neuronal firing. Also, electrical stimulation inhibits the nervous tissue downstream of the stimulation site by preventing the passage of nervous activity from the upstream to the downstream of the axon., Conclusion: Neurostimulation techniques consisting of LFS and HFS have a potential role in treating epileptiform activity, with some studies having positive results. Further investigations with larger sample sizes and standardized outcome measures can be conducted to validate the results of previous studies., Competing Interests: The authors declare that they have no competing interests., (© 2023 Iran University of Medical Sciences.)