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There is increasing evidence that oxidative stress is a causal factor in different neurodegenerative disorders such as Alzheimer's disease and epilepsy. High-fat diet (HFD) has been shown to induce oxidative stress and neuronal damage that may increase susceptibility to seizures. The present study was undertaken to investigate the relationships between vitamin E, a potent antioxidant, HFD, and chemically induced seizures, using the PTZ seizure model in rats. Animals were randomly assigned into four groups: control, HFD, vitamin E (Vit E), and high-fat diet with vitamin E (HFD + Vit E) group. Vitamin E and/or HFD were administered to animals for 6 weeks. Thereafter, PTZ seizure threshold was measured in control and treated rats, and different brain regions were analyzed for levels of oxidative stress biomarkers. Current results revealed a significant reduction in PTZ seizure threshold in rats consuming HFD, which could be prevented by vitamin E supplement. Alongside, vitamin E supplement prevented HFD induced changes in oxidative stress biomarkers and capacity enzymes. Therefore, current results suggest that prolonged consumption of HFD increases susceptibility to PTZ induced seizures, which may be related to HFD induced oxidative stress. This increase in the PTZ susceptibility could be prevented by the administration of vitamin E, probably through its antioxidant effect, particularly at the brain hippocampal region. - 2019 Elsevier Inc. The study was funded by grant no. 214/2015 to KA from the Deanship of Research of the Jordan University of Science and Technology . Scopus

The nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor is a member of the opioid receptor superfamily with N/OFQ as its endogenous agonist. Wide expression of the NOP receptor and N/OFQ, both centrally and peripherally, and their ability to modulate several biological functions has led to development of NOP receptor modulators by pharmaceutical companies as therapeutics, based upon their efficacy in preclinical models of pain, anxiety, depression, Parkinson’s disease, and substance abuse. Both posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) are debilitating conditions that significantly affect the quality of life of millions of people around the world. PTSD is often a consequence of TBI, and, especially for those deployed to, working and/or living in a war zone or are first responders, they are comorbid. PTSD and TBI share common symptoms, and negatively influence outcomes as comorbidities of the other. Unfortunately, a lack of effective therapies or therapeutic agents limits the long term quality of life for either TBI or PTSD patients. Ours, and other groups, demonstrated that PTSD and TBI preclinical models elicit changes in the N/OFQ-NOP receptor system, and that administration of NOP receptor ligands alleviated some of the neurobiological and behavioral changes induced by brain injury and/or traumatic stress exposure. Here we review the past and most recent progress on understanding the role of the N/OFQ-NOP receptor system in PTSD and TBI neurological and behavioral sequelae. There is still more to understand about this neuropeptide system in both PTSD and TBI, but current findings warrant further examination of the potential utility of NOP modulators as therapeutics for these disorders and their co-morbidities. We advocate the development of standards for common data elements (CDE) reporting for preclinical PTSD studies, similar to current preclinical TBI CDEs. That would provide for more standardized data collection and reporting to improve reproducibility, interpretation and data sharing across studies.

There is increasing evidence advocating for the causal association between oxidative stress and different neurodegenerative disorders such as Alzheimer disease and epilepsy. We have previously shown that consumption of High-fat diet (HFD) induces oxidative stress, which results in hippocampal neuronal damage hence impairment of learning and memory. This impairment was prevented by antioxidants. The reported damage in the hippocampus caused by oxidative stress following consumption of HFD could alter synaptic transmission in the hippocampus and may increase susceptibility to seizures. The present study was undertaken to determine if chronic consumption of HFD changes susceptibility to chemically induced seizures using the pentylenetetrazol (PTZ) seizure threshold model in rats. In this study, HFD was administered to animals for 6 weeks. Thereafter, the PTZ seizure threshold was measured in control and HFD rats. Different brain regions were analyzed for the levels of oxidative stress biomarkers. Results revealed a significant reduction (50.0 ± 2.5%) in PTZ seizure threshold in rats consuming HFD. This was accompanied by a decrease in the oxidative stress biomarkers and capacity enzymes such as reduced/oxidized glutathione (GSH/GSSG) ratio, glutathione peroxidase (GPx) and catalase activities and increase in oxidized glutathione (GSSG) levels in the hippocampus and cortex regions of the brain of HFD rats. Collectively, current data suggest that prolonged consumption of HFD increases susceptibility to PTZ-induced seizures. Such an effect may be related to HFD- induced oxidative stress in the brain.

Post-traumatic stress disorder (PTSD) is a mental health disorder that can develop after a terrifying or life threatening event. Multiple symptoms are noticed in patients with PTSD including cognitive impairment, which was shown to be is associated with oxidative stress. Tempol is a highly efficient membrane-permeable antioxidant. In this study, we investigated the possible protective effect of tempol on PTSD-induced memory impairment. To test this hypothesis, we used single prolonged stress (SPS) model (2h restrain, 20min forced swimming, 15min rest, and 1-2min diethyl ether exposure) as a model of PTSD. Rats were randomly assigned into four groups: control (provided distilled water), tempol (provided tempol; 80mg/kg/day by oral gavage for 4weeks), SPS (exposed to prolonged stress and administered distilled water) and tempol/SPS (exposed to prolonged stress and administered tempol for 4weeks). We used radial arm water maze to test spatial learning and memory functions and enzyme-linked immunosorbant assay (ELISA) to measure levels of oxidative stress biomarkers in the hippocampus. Results showed that SPS model of PTSD impaired both short and long-term memories (P