## 4 Discussion
The obtained findings in this study revealed the neuro-inflammatory response to the PTZ injection, which is indicated by the markedly elevated protein levels of pro-inflammatory cytokines (TNF-\(\alpha\), IL-1\(\beta\), IL-6, and NF-\(\kappa\)B) in the cerebral cortex tissue. Moreover, GFAP was significantly increased following PTZ injection, indicating the astrocytes activation that leads to inflammatory and apoptotic responses in the brain [56]. It was obvious in this study that SAE-SeNPs reduced the levels of the measured pro-inflammatory cytokines and GFAP expression, resulting in its anti-inflammatory activity against PTZ-induced neuroinflammation. This protective effect is mostly attributed to the flavonoids, phenolics, and GSH componentsof the SAE, which may prevent the free radical's accumulation and reduce the oxidative stress and its consequent inflammation and apoptosis [57, 58]. Furthermore, SeNPs were reported to reduce the gamma aminobutyric acid levels in the brain of rats, resulting in a reduction in many inflammatory cytokines and oxidant compounds, and can decrease the congested blood vessels in the cerebral cortex as well [59]. Since oxidative stress ended by cellular apoptosis and epileptic seizures enhance cerebral ischemia ended by neuronal death [26], the apoptotic biomarkers were evaluated in this study. Following the PTZ injection, there were elevations in pro-apoptotic proteins (Bax and caspase-3) concurrent with a decline in anti-apoptotic (Bcl-2) protein levels; however, these abnormalities were restored to normal levels after treatment with SAE-SeNPs. As noticed in this study, SAE-SeNPs had an antioxidant activity that was able to reduce the oxidative stress and the consequent mitochondrial stress via reducing Bax level and elevating Bcl-2 levels, thereby exerting its anti-apoptotic effect. The resulted anti-apoptotic effect might be related to the anti-inflammatory and anti-apoptotic properties of SAE [58]. Additionally, biosynthesized nano-selenium inhibited cadmium-induced neuronal loss via decreasing Bax and increasing Bcl-2 levels [60]. Moreover, SeNPs showed an anticonvulsant effect via their anti-apoptotic effect in the cerebral cortex tissues of rats [3]. It is well-known that NE as a neurotransmitter is playing a crucial role in preventing epilepsy-induced seizures and neuronal changes [61]. It was reported that a high NE concentration in the cerebral cortex tissues can prevent pilocarpine-induced seizures [62]. Thus, it was reasonable to measure the NE cortical levels in this study to know whether it affects the anti-epileptic effect of SAE-SeNPs or not. The obtained results showed a substantial decrease in NE cortical levels following the PTZ injection. The PTZ-induced NE reduction was treated with SAE-SeNPs, showing its significant anti-epileptic effect. These data demonstrate the resultant seizures because the decrease in neurotransmitters triggers seizures and develops many neuropathological disorders as reported previously [63, 64]. Acetylcholine is an important neurotransmitter present in postsynaptic neuromuscular junctions. Meanwhile, AChE hydrolyzes acetylcholine. The disturbance in the AChE activity results in cholinergic dysfunction, which is closely related to the epileptic mechanism because of the imbalance between neuronal excitation and inhibition [65]. In this study, AChE activity increased significantly after PTZ injection, meanwhile SAE-SeNPs treatment significantly reduced AChE activity, demonstrating its antiseizure effect. Elevated AChE activity in epileptic rats was reported because of oxidative stress in the cortical tissues [3]. In the current study, SAE-SeNPs revealed an anti-epileptic effect via modulating the neurotransmitters and reducing the oxidative stress. Although the anti-epileptic activity of SAE has not been reported yet, the neuroprotective effect of SeNPs has been studied, revealing their potential protective effect against many neurological diseases through their antioxidant and anti-inflammatory activities [3, 17, 66].