<p>Selenium Nanoparticles Pre-Treatment Reverse Behavioral, Oxidative Damage, Neuronal Loss and Neurochemical Alterations in Pentylenetetrazole-Induced Epileptic Seizures in Mice</p>

Abstract

Introduction: Epilepsy is a chronic neurological condition characterized by behavioral, molecular, and neurochemical alterations. Current antiepileptic drugs are associated with various adverse impacts. The main goal of the current study is to investigate the possible anticonvulsant effect of selenium nanoparticles (SeNPs) against pentylenetetrazole (PTZ)mediated epileptic seizures in mice hippocampus. Sodium valproate (VPA) was used as a standard anti-epileptic drug. Methods: Mice were assigned into five groups (n=15): control, SeNPs (5 mg/kg, orally), PTZ (60 mg/kg, intraperitoneally), SeNPs+PTZ and VPA (200 mg/kg)+PTZ. All groups were treated for 10 days. Results: PTZ injection triggered a state of oxidative stress in the hippocampal tissue as represented by the elevated lipoperoxidation, heat shock protein 70 level, and nitric oxide formation while decreased glutathione level and antioxidant enzymes activity. Additionally, the blotting analysis showed downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the epileptic mice. A state of neuroinflammation was recorded following the developed seizures represented by the increased pro-inflammatory cytokines. Moreover, neuronal apoptosis was recorded following the development of epileptic convulsions. At the neurochemical level, acetylcholinesterase activity and monoamines content were decreased in the epileptic mice, accompanied by high glutamate and low GABA levels in the hippocampal tissue. However, SeNP supplementation was found to delay the onset and decreased the duration of tonic, myoclonic, and generalized seizures following PTZ injection. Moreover, SeNPs were found to provide neuroprotection through preventing the development of oxidative challenge via the upregulation of Nrf2 and HO-1, inhibiting the inflammatory response and apoptotic cascade. Additionally, SeNPs reversed the changes in the activity and levels of neuromodulators following the development of epileptic seizures. Conclusion: The obtained results suggest that SeNPs could be used as a promising anticonvulsant drug due to its potent antioxidant, anti-inflammatory, and neuromodulatory activities.

Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy

“…A similar diminution of oxidative damage was noted in rats where epilepsy was evoked with kainic acid [15]. Limited cerebral territories can manufacture new nerve cells; however, the hippocampal DG is one of them [36]. The role of the DG in the onset of TLE is well recognized.…”

“…Limited cerebral territories can manufacture new nerve cells; however, the hippocampal DG is one of them [ 36 ]. The role of the DG in the onset of TLE is well recognized.…”

Genistein Protects Epilepsy-Induced Brain Injury Through Regulating The JAK2/STAT3 and Keap1/Nrf2 Signaling Pathways in The Developing Rats

“…At present, the pathogenesis of epilepsy is not clear. The existing antiepileptic drugs primarily suppress neuronal excitability by regulating neurotransmitter receptors (such as glutamate, GABA and acetylcholine) or ion channels [29,30,31] . These are in fact anticonvulsant medications rather than antiepileptic treatments, as they do not target the implicit underlying etiology.…”

Neurotrophic Factors in Parkinson’s Disease: Clinical Trials, Open Challenges and Nanoparticle-Mediated Delivery to the Brain

“…Similarly, several inorganic NPs were neuroprotective against inflammation and reactive oxygen species (ROS). For example, selenium NPs reversed oxidative damage and neuronal loss in a mouse model of epilepsy ( Yuan et al, 2020 ) and cerium oxide NPs blocked pro-inflammatory signaling and drove microglial transformation from a pro-inflammatory phenotype to an anti-inflammatory phenotype under pathological conditions in microglial cell line BV-2 ( Zeng et al, 2018 ). Similarly, biomimetic NPs coated with the cell membranes of neuronal cells promoted the transformation of microglia into the anti-inflammatory phenotype to relieve neuroinflammation and recover dopamine levels in a mouse model of PD ( Liu et al, 2020 ).…”