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Demyelination is among the most conspicuous neurological sequelae of SARS-CoV-2 infection (COVID-19) in both the central (CNS) and peripheral (PNS) nervous systems. Several hypotheses have been proposed to explain the mechanisms underlying demyelination in COVID-19. However, none have considered the SARS-CoV-2's effects on the renin-angiotensin-aldosterone system (RAAS). Therefore, our objective in this review is to evaluate how RAAS imbalance, caused by direct and indirect effects of SARS-CoV-2 infection, could contribute to myelin loss in the PNS and CNS. In the PNS, we propose that demyelination transpires from two significant changes induced by SARS-CoV-2 infection, which include upregulation of ADAM-17 and induction of lymphopenia. Whereas, in the CNS, demyelination could result from RAAS imbalance triggering two alterations: (1) a decrease in angiotensin type II receptor (AT2R) activity, responsible for restraining defense cells' action on myelin; (2) upregulation of ADAM-17 activity, leading to impaired maturation of oligodendrocytes and myelin formation. Thus, we hypothesize that increased ADAM-17 activity and decreased AT2R activity play roles in SARS-CoV-2 infection-mediated demyelination in the CNS., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics Approval: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Intrahippocampal pilocarpine microinjection (H-PILO) induces status epilepticus (SE) that can lead to spontaneous recurrent seizures (SRS) and neurodegeneration in rodents. Studies using animal models have indicated that lectins mediate a variety of biological activities with neuronal benefits, especially galectin-1 (GAL-1), which has been identified as an effective neuroprotective compound. GAL-1 is associated with the regulation of cell adhesion, proliferation, programmed cell death, and immune responses, as well as attenuating neuroinflammation. Here, we administrated GAL-1 to Wistar rats and evaluated the severity of the SE, neurodegenerative and inflammatory patterns in the hippocampal formation. Administration of GAL-1 caused a reduction in the number of class 2 and 4 seizures, indicating a decrease in seizure severity. Furthermore, we observed a reduction in inflammation and neurodegeneration 24 h and 15 days after SE. Overall, these results suggest that GAL-1 has a neuroprotective effect in the early stage of epileptogenesis and provides new insights into the roles of exogenous lectins in temporal lobe epilepsy (TLE)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Status epilepticus (SE) is defined as continuous and self-sustaining seizures, which trigger hippocampal neurodegeneration, mitochondrial dysfunction, oxidative stress, and energy failure. During SE, the neurons become overexcited, increasing energy consumption. Glucose uptake is increased via the sodium glucose cotransporter 1 (SGLT1) in the hippocampus under epileptic conditions. In addition, modulation of glucose can prevent neuronal damage caused by SE. Here, we evaluated the effect of increased glucose availability in behavior of limbic seizures, memory dysfunction, neurodegeneration process, neuronal activity, and SGLT1 expression. Vehicle (VEH, saline 0.9%, 1 μL) or glucose (GLU; 1, 2 or 3 mM, 1 μL) were administered into hippocampus of male Wistar rats (Rattus norvegicus) before or after pilocarpine to induce SE. Behavioral analysis of seizures was performed for 90 min during SE. The memory and learning processes were analyzed by the inhibitory avoidance test. After 24 h of SE, neurodegeneration process, neuronal activity, and SGLT1 expression were evaluated in hippocampal and extrahippocampal regions. Modulation of hippocampal glucose did not protect memory dysfunction followed by SE. Our results showed that the administration of glucose after pilocarpine reduced the severity of seizures, as well as the number of limbic seizures. Similarly, glucose after SE reduced cell death and neuronal activity in hippocampus, subiculum, thalamus, amygdala, and cortical areas. Finally, glucose infusion elevated the SGLT1 expression in hippocampus. Taken together our data suggest that possibly the administration of intrahippocampal glucose protects brain in the earlier stage of epileptogenic processes via an important support of SGLT1.

Status epilepticus (SE) can lead to serious neuronal damage and act as an initial trigger for epileptogenic processes that may lead to temporal lobe epilepsy (TLE). Besides promoting neurodegeneration, neuroinflammation, and abnormal neurogenesis, SE can generate an extensive hypometabolism in several brain areas and, consequently, reduce intracellular energy supply, such as adenosine triphosphate (ATP) molecules. Although some antiepileptic drugs show efficiency to terminate or reduce epileptic seizures, approximately 30% of TLE patients are refractory to regular antiepileptic drugs (AEDs). Modulation of glucose availability may provide a novel and robust alternative for treating seizures and neuronal damage that occurs during epileptogenesis; however, more detailed information remains unknown, especially under hypo- and hyperglycemic conditions. Here, we review several pathways of glucose metabolism activated during and after SE, as well as the effects of hypo- and hyperglycemia in the generation of self-sustained limbic seizures. Furthermore, this study suggests the control of glucose availability as a potential therapeutic tool for SE.