The new coronavirus has spread throughout the world in a very short time and now has become a pandemic. Most infected people have symptoms such as dry cough, dyspnea, tiredness, and fever. However, the Covid-19 infection disrupts various organs, including the liver, kidney, and nervous system. Common neurological symptoms of the Covid-19 infection include delirium, confusion, headache, and loss of sense of smell and taste. In rare cases it can cause stroke and epilepsy. The virus enters the nervous system either directly through nerve pathways or indirectly through the ACE2 receptor. The neurological symptoms of a Covid-19 infection in the brain are mainly due to either the entry of pro-inflammatory cytokines into the nervous system or the production of these cytokines by microglia and astrocytes. Pro-inflammatory cytokines can cause blood-brain barrier disruption, increase in glutamate and aspartate and reduce GABA levels, impairs the function of ion channels, and finally, high levels of cytokines can cause epilepsy. Understanding the potential mechanisms is necessary to gain better insight into COVID-19 induced seizure pathogenesis and to design the correct treatment strategies to achieve appropriate treatment for seizure and epilepsy.

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Background: Pathological conditions, including ischemic stroke, are associated with severe Endoplasmic Reticulum (ER) stress that induces apoptosis and cell death. Herbal medicines are natural treatments with few side effects in such situations. Objectives: In the present study, we examined the probable neuroprotective effects of Viola spathulata, Lamium album, and Urtica dioica on splicing of ER stress mRNA gene marker (X-box Binding Protein-1 [XBP-1]) and Unfolded Protein Response (UPR) activation in the brain of the rat stroke model. Materials & Methods: Sixty male Wistar albino rats (weight: 220-250 g) were selected for this study and divided into two major groups. The first major group comprised the healthy animals that are subdivided into groups number 1 to 5. The second major group comprised the Middle Cerebral Artery Occlusion (MCAO) group subdivided into groups number 6-10. The reverse transcriptionpolymerase chain reaction was performed after pretreatment with different herbal extracts (5, 10 mg/kg), Viola spathulata, and 100 mg/ kg Urtica dioica and Lamium album). The results were analyzed by one-way analysis of variance in IBM SPSS v. 22. Results: MCAO-induced ischemia caused a marked increase in XBP-1 splicing in all rats of the MCAO group in comparison to the control groups (P<0.05), and pretreatment with 3 herbal extracts dramatically decreased target gene splicing in the MCAO studied groups (P<0.05). Conclusion: All three herbal extracts of U. dioica, L. album, and V. spathulata had the promising potential to use as a neuroprotective agent by reducing ER stress.

Although further studies are needed to clarify the mechanisms of time course of neuroprotection, HO partly is associated with expression of NCX1 consistent with an active role in the genesis of ischaemic neuroprotection.