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Modulation of Glucose Availability and Effects of Hypo- and Hyperglycemia on Status Epilepticus: What We Do Not Know Yet?

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Abstract

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.

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Funding

DLGG was supported by the Research Productivity Scholarship Program in Brazilian National Council for Scientific and Technological Development (CNPq). We thank CAPES-Brazil for PhD Research Fellowship to ISM, YMOS, ALDP, and LCS. Sabino-Silva, R received a fellowship from PrInt CAPES/UFU. This project was supported by FAPEAL, FAPEMIG (APQ-02872-16), and National Institute of Science and Technology in Theranostics and Nanobiotechnology - INCT-Teranano (CNPq-465669/2014-0).

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ISM, RSS, and OWC conceived the original idea and designed the outlines of the study. ISS, ALDP, YMOS, LMF, and DCSPN wrote the draft of the manuscript. ISS, ALDP, and OWC prepared the figures for the manuscript. ISS, LCS, MD, DLGG, CQT, RSS, and OWC performed the literature review and aided in revising the manuscript. All authors have read and agreed to the final version of the manuscript.

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Correspondence to Robinson Sabino-Silva or Olagide Wagner de Castro.

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de Melo, I.S., Pacheco, A.L.D., dos Santos, Y.M.O. et al. Modulation of Glucose Availability and Effects of Hypo- and Hyperglycemia on Status Epilepticus: What We Do Not Know Yet?. Mol Neurobiol 58, 505–519 (2021). https://doi.org/10.1007/s12035-020-02133-8

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