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, ArzuhanBackground: 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 A Rare Presentation of Bilateral Periventricular Nodular Heterotopia With Intra-Axial Pontine Lesion: A Case Report and Treatment Approach(Elsevier, 2024) Shenno, Milad; Al-Qiami, Almonzer; Ibrahim, Ismail A.; Elhaw, Lojin; Nashwan, Abdulqadir J.This report presents a rare case of a 19-year-old male with bilateral periventricular nodular heterotopia (PVNH), a congenital brain abnormality resulting from failed neural cell migration, along with an intra-axial pontine lesion of unknown pathology. The differential diagnosis of childhood brainstem tumors in such cases commonly includes diffuse midline glioma (DMG), which is associated with a dismal prognosis due to H3 K27 gene mutation. However, this case exhibits a unique focal dorsal exophytic brainstem glioma variant, accounting for only a small percentage (approximately 10 %) of pontine tumors and carrying a more favorable prognosis. The lesion is suspected to be a pilocytic astrocytoma, presenting distinct neurological symptoms. In this case, the patient presented with symptoms include mainly occasional tonic-clonic seizures, right side mild spasticity with ataxic gait and right eye blurring of vision along with right side facial palsy. The patient's clinical evaluation, in conjunction with various medical diagnostic tests and MRI with and without contrast, led to the final diagnosis. Management began with anti-epileptic medication, with a plan for further treatment and follow-up.