WoS İndeksli Yayınlar Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.14627/6

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  • Article
    Metformin Attenuates PTZ-Induced Seizures and Cognitive Impairment and Is Associated with Altered NOS/NO Signaling: Combined in Vivo and in Silico Evidence
    (Taylor & Francis Ltd, 2026) Ciltas, Arzuhan Cetindag; Sahin, Bilal; Hacisuleyman, Levent; Çetindağ Çiltaş, Arzuhan
    Background: Epilepsy remains a major neurological disorder with high rates of drug resistance and cognitive decline. Repurposing neuroprotective drugs offers a promising approach. Metformin, a widely used antidiabetic agent, has shown anticonvulsant effects, yet its impact on nitric oxide synthase (NOS) isoforms in distinct brain regions remains unclear. Methods: Adult male Wistar rats were allocated into control, pentylenetetrazole (PTZ), or metformin+PTZ groups. Metformin (200 mg/kg, i.p.) was administered for 7 days before induction of acute PTZ seizures (45 mg/kg, i.p.). Seizure severity and latency were assessed using Racine's scale, and cognition was evaluated by the passive avoidance test (PAT). Nitric oxide (NO) and the expression of its synthesizing enzymes, inducible (iNOS), neuronal (nNOS), and endothelial (eNOS), were quantified in the cortex and hippocampus via enzyme-linked immunosorbent assay (ELISA). In silico analyses included target prediction and molecular docking to assess metformin - NOS interactions. Results: Metformin significantly reduced seizure severity, prolonged latency to the first myoclonic jerk, and prevented PTZ-induced memory impairment (all p < 0.001). These behavioral effects were accompanied by reductions in cortical and hippocampal nNOS and iNOS expression, decreased cortical eNOS levels, and lower NO accumulation. TargetNet predicted NOS isoforms among potential metformin targets, and docking indicated moderate binding affinity (-5.2 to -5.9 kcal/mol). Conclusion: Metformin exerted seizure-suppressing and cognition-preserving effects in an acute PTZ model, associated with reductions in NOS isoform expression and NO levels, suggesting altered NOS/NO signaling and supporting its potential as an adjunctive candidate for mitigating seizure-related neuronal dysfunction.
  • Article
    Unraveling the Potential of Stem Cell Therapy in Motor Neuron Disease: A Narrative Review
    (Bentham Science Publ, 2025) Essa, Syed Muhammad; Khosa, Noor Ahmed; Kakar, Amanullah; Ozturk, Basar; Ibrahim, Ismail A.; Haq, Noman
    Motor neuron disorders (MNDs), including ALS, are deadly neurodegenerative conditions that cause progressive motor neuron degeneration. With neuroprotection and the potential for neuron regeneration employing MSCs, ESCs, iPSCs, and NSCs, stem cell treatment presents a viable alternative to current medicines, which only control a limited number of symptoms. Following PRISMA criteria, this narrative review methodically screened 1248 records from the Cochrane, Web of Science, PubMed, and Scopus databases. Following a thorough screening process, 22 studies, including preclinical models and 19 clinical trials, were analysed to assess the therapeutic mechanisms, safety, and efficacy of stem cell therapies for MNDs. Mesenchymal stem cell (MSC) therapy has shown a promising safety profile and possible therapeutic efficacy in ALS, with no substantial transplant-related toxicity noted. ALS functional rating scale-revised (ALSFRS-R) scores and forced vital capacity (FVC) assessments from clinical trials, such as those evaluating autologous bone marrow-derived MSCs, demonstrated stabilisation in ALS development. Studies have also emphasised as to how immunomodulation and neurotrophic factors play a part in MSC-based therapies. Recent data indicate that repeated intrathecal MSC injection could extend the duration of therapeutic advantages. Clinical trials have shown safety and early efficacy signals for motor neurons produced from embryonic stem cells (ESCs), especially using AstroRx (R). This suggests that ESCs could be a viable option for regenerative medicine. Nonetheless, issues, like host integration and differentiation optimisation, still exist. Although clinical translation is still in its early stages, induced pluripotent stem cells (iPSCs) and their derivatives provide disease modelling and patient-specific therapeutic applications. Stem cell therapy holds promise for treating MND, with MSCs leading the way in current trials. It is necessary to enhance ESC- and iPSC-based techniques to tackle integration issues. To ensure long-term safety and efficacy, therapies must be developed using standardised protocols, patient stratification, optimised delivery, and large-scale studies.