Hadwa Ali Abd-Alkhalek

Status epilepticus (SE), the most severe form of epilepsy, leads to brain damage. Uncertainty persists about the mechanisms that lead to the pathophysiology of epilepsy and the death of neurons. Overloading of intracellular iron ions has recently been identified as the cause of a newly recognized form of controlled cell death called ferroptosis. Inhibiting ferroptosis has shown promise as a treatment for epilepsy, according to recent studies. So, the current study aimed to assess the possible antiepileptic impact of CoQ10 either alone or with the standard antiepileptic drug sodium valproate (SVP) and to evaluate the targeted effect of COQ10 on hippocampal oxidative stress and ferroptosis in a SE rat model. Using a lithium-pilocarpine rat model of epilepsy, we evaluated the effect of SVP, CoQ10, or both on seizure severity, histological, and immunohistochemical of the hippocampus. Furthermore, due to the essential role of oxidative stress and lipid peroxidation in inducing ferroptosis, we evaluated malonaldehyde (MDA), reduced glutathione (GSH), glutathione peroxidase 4 (GPX4), and ferritin in tissue homogenate. Our work illustrated that ferroptosis occurs in murine models of lithium-pilocarpine-induced seizures (epileptic group). Nissl staining revealed significant neurodegeneration. A significant increase in the number of astrocytes stained with an astrocyte-specific marker was observed in the hippocampus. Effective seizure relief can be achieved in the seizure model by administering CoQ10 alone compared to SVP. This was accomplished by lowering ferritin levels and increasing GPX4, reducing MDA, and increasing GSH in the hippocampus tissue homogenate. In addition, the benefits of SVP therapy for regulating iron stores, GPX4, and oxidative stress markers were amplified by incorporating CoQ10 as compared to SVP alone. It was concluded that CoQ10 alone has a more beneficial effect than SVP alone in restoring histological structures and has a targeted effect on hippocampal oxidative stress and ferroptosis. In addition, COQ10 could be useful as an adjuvant to SVP in protecting against oxidative damage and ferroptosis-related damage that result from epileptic seizures.

Background: The consumption of fast- food is increasing among children, adolescents and adults. Carbonated drinks as Diet Coke are widely consumed with fast food. One of the thousands of chemicals used in our new high-tech foods is the monosodium glutamate (MSG). Aim of the study: This study was conducted to investigate the effect of Diet Coke and monosodium glutamate salt either separately or in combination on the cerebellar cortex of adult male albino rats.Materials and Methods: Forty adult male albino rats were divided into four groups. Group I: control group. Group II (Diet Coke group) which was subdivided into: subgroup IIA: each rat received 2.5 ml of Diet Coke twice daily by oral gavage and subgroup IIB: rats received Diet Coke instead of water throughout the day. Group III (MSG group): rats received MSG salt solution (3 gm MSG / kgm) by oral gavage once daily. Group IV (combination group) rats received combination of MSG solution and Diet Coke. This group was subdivided into two subgroups. Subgroup IVA: rats received MSG salt solution in the same dose as group III and 2.5 ml of Diet Coke twice daily, by oral gavage. Subgroup IVB: rats received MSG salt solution in the same dose as group III and Diet Coke instead of water throughout the day. At the end of the experiment (21 days) cerebella were dissected out and processed for histological, immunohistochemical and morphometric studies. Results: Histological examination of the cerebellar cortex revealed that both Diet Coke and MSG either separately or in combination resulted in degenerative changes that were more significant in the combination group.Conclusion: Diet Coke and MSG induced degenerative changes in the cerebellar cortex that was more significant in their combination.

Several hypotheses link high fat diet (HFD) with the pathophysiology of depression and its response to antidepressants. This study aimed to determine the effect of metformin (MET) on the cognitive and antidepressant activity of fluoxetine (FLU) through its effect on c-Jun expression. Behavioral, cognitive function, biochemical, and histopathological studies were performed in non-HFD- and HFD-fed rats exposed to chronic restraint stress (CRS). Stressed group showed cognitive impairment, depressive-like symptoms, disturbed glucose homeostasis and lipid profile, reduced adiponectin level, brain-derived neurotrophic factor (BDNF) expression, and increased corticosterone and c-Jun. All these were aggravated by HFD. MET, FLU and their combination produced significant improvement in lipid profile with significant increase in adiponectin and BDNF expression. Corticosterone, body weight and insulin resistance showed significant decrease in the treated groups. Moreover, there was a significant decrease in hippocampal c Jun expression. There was a significant preferable effect toward the combination. Conclusion, MET may decrease the refractoriness to FLU and improves the cognition in individuals who are fed on HFD.