## 4 Discussion  
Selenium nanoparticles have been recommended to be used in many therapeutic protocols of different diseases as a co-therapy because of their biocompatibility and improved cellular uptake [43]. In this study, we hypothesized that green synthetized SeNPs using SAE might protect against PTZ-stimulated epileptic seizures in rats. This hypothesis was based on the reported therapeutic properties of both SeNPs and SAE separately [3; 44]. Therefore, the synthesis of SeNPs using SAE potentiate their protective efficiency, and this was investigated in the current study on cortical damage and epileptic seizures in rats. The data obtained in this study confirmed that a single injection of PTZ was able to induce a convulsive effect, as indicated by the recorded seizures and cortical oxidative stress (elevated MDA and NO levels). Moreover, the antioxidant molecules (CAT, GPx, and GR) were exhausted and reduced following PTZ injection. The neuronal antioxidant response is controlled by the transcriptional factor Nrf2 gene expression, which was downregulated as well following the PTZ injection. The pathogenesis of PTZ-induced epileptic seizures is related to the ROS production and the depletion of enzymatic and non-enzymatic antioxidants during epileptogenesis [8]. Moreover, the high level of NO can interact with superoxide anions producing peroxynitrite radicals that lead to deleterious neurological effects [45; 46]. The oxidative stress and the associated neuronal hyperexcitability result in neuronal cell death (apoptosis) at the end [47; 48], which is indicated in our findings by the elevated pro-apoptotic molecules (Bax and caspase-3) and reduced anti-apoptotic molecule (Bcl-2) following PTZ injection. The PTZ-induced signal transduction and molecular changes are confirmed by our findings of apoptotic markers. SeNPs with their nanosize and large surface area were reported for their potent antioxidant effects by enhancing free radicals scavenging, and inhibiting ROS generation [49]. SeNPs can reduce PTZ-induced neuronal oxidative damage by inhibiting ROS generation and upregulating Nrf2 and heme oxygenase-1 enzyme (HO-1) in the cerebral cortex tissue [3]. Moreover, neurobehavioral disorders and neuronal lipid peroxidation in the brain of diabetic rats were alleviated by a combination of SeNPs and metformin [50]. Our findings revealed the antioxidant effect of SAE-SeNPs against the PTZ-induced oxidative stress in the cortical tissues of rats that might explain the reduction in seizure duration after SAE-SeNPs supplementation. The ability of SAE-SeNPs to reduce the MDA, NO levels, and to increase the activities of enzymatic and non-enzymatic antioxidants (GSH, SOD, CAT, GPx, and GR) can be related to the flavonoid and phenolic content of SAE [51]. [PERSON] et al. [44] reported that _S. aromatic_ ethanolic extracts have potent antioxidant properties and can alleviate oxidative stress in brain tissues in amyloid beta-induced Alzheimer's disease-like pathology in rats. Moreover, SeNPs itself might be responsible for the resultant antioxidant capacity via inhibiting ROS accumulation, cytotoxicity, and protecting the antioxidant enzymes activities [52]. Therefore, the current oxidant/antioxidant profile of SAE-SeNPs showed potential and significant antioxidant activity in the epileptic cortical tissues. The release of pro-inflammatory cytokines including TNF-\(\alpha\), IL-6, and IL-1\(\beta\) is the result of NF-\(\kappa\)B signal transduction that is activated by ROS generation [53; 54]. IL-1\(\beta\) can upregulate the cyclooxygenase-2 (Cox-2) enzyme's gene expression that converts arachidonic acid to prostaglandamins. Prostaglandin is a precursor of prostacyclin that is expressed in the inflammatory response and stimulates astrocytes to produce glutamate, resulting in seizure-associated neuro-excitability [55].