Role of Modulation of Hippocampal Glucose Following Pilocarpine-Induced Status Epilepticus

Melo, Igor Santana de; Santos, Yngrid Mickaelli Oliveira dos; Pacheco, Amanda Larissa Dias; Costa, Mariana Ivo; Silva, Vanessa de Oliveira; Freitas-Santos, Jucilene; Cavalcante, Cibelle de Melo Bastos; Silva-Filho, Reginaldo; Leite, Antônio Cesar Rios; Gitaí, Daniel Góes Leite; Duzzioni, Marcelo; Sabino-Silva, Robinson; Borbely, Alexandre Urban; Castro, Olagide Wagner de

doi:10.1007/s12035-020-02173-0

Cited by 10 publications

(6 citation statements)

References 120 publications

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“…TCA cycle intermediates, including citrate and α‐ketoglutarate, show significantly higher concentrations in Alzheimer's disease 36 . Hippocampal mitochondrial dysregulation, oxidative stress, and cell death were observed in pilocarpine‐induced SE models 37,38 . TCA cycle dysregulation may be associated with neuronal excitability, gliosis, inflammation, and apoptosis in children with SE with poor outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

Wang

et al. 2023

CNS Neurosci Ther

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AimsStatus epilepticus (SE) is the most common neurological emergency in pediatric patients. This study aimed to screen for prognostic biomarkers of SE in the cerebrospinal fluid (CSF) using metabolomics.MethodsUltra‐performance liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐QTOF‐MS) was conducted to identify prognostic biomarkers in CSF metabolomics by comparing the poor outcome group (N = 13) with the good outcome group (N = 15) of children with SE. Differentially expressed metabolites were identified using Mann–Whitney U test corrected by Benjamini‐Hochberg and partial least squares discriminant analysis (PLS‐DA).ResultsThe PLS‐DA model identified and validated significant metabolic differences between the poor and good outcome groups of children with SE (PLS‐DA with R2Y = 0.992 and Q2 = 0.798). A total of 49 prognosis‐related metabolites were identified. Of these metabolites, 20 including glutamyl‐glutamine, 3‐iodothyronamine, and L‐fucose had an area under the curve (AUC) ≥ 80% in prognostic prediction of SE. The logistic regression model combining glutamyl‐glutamine and 3‐iodothyronamine produced an AUC value of 0.976, with a sensitivity of 0.863 and specificity of 0.956. Pathway analysis revealed that dysregulation of the citrate cycle (TCA) and arginine biosynthesis may contribute to poor SE prognosis.ConclusionsThis study highlighted the prognosis‐related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl‐glutamine and 3‐iodothyronamine with high predictive value was established.

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Section: Discussionmentioning

confidence: 99%

“…36 Hippocampal mitochondrial dysregulation, oxidative stress, and cell death were observed in pilocarpine-induced SE models. 37,38 TCA cycle dysregulation may be associated with neuronal excitability, gliosis, inflammation, and apoptosis in children with SE with poor outcomes.…”

Section: Discussionmentioning

confidence: 99%

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

Wang

et al. 2023

CNS Neurosci Ther

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“…Taken together, these data could explain the reason why the OS caused by DM2 under our experimental conditions is not greater than the one caused by SE under normoglycemic conditions. In addition, in a recent study, it was shown that glucose control before and after SE does not interfere with the establishment of brain OS 44 …”

Section: Discussionmentioning

confidence: 93%

“…In addition, in a recent study, it was shown that glucose control before and after SE does not interfere with the establishment of brain OS. 44 …”

Section: Discussionmentioning

confidence: 99%

“…In addition, in a recent study, it was shown that glucose control before and after SE does not interfere with the establishment of brain OS. 44 A limitation of our study is that we evaluated the early stages of DM2, and brain changes could be less pronounced compared with the advanced stages of the disease. Although we analyzed ROS, it would also be relevant to study RNS and enzymes involved in counteracting OS, which would help us to understand the relationship between DM2 and seizures.…”

Section: Correlation Among Glycemia and Lipid Peroxidation Or Reactiv...mentioning

confidence: 98%

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Type 2 diabetes mellitus facilitates status epilepticus in adult rats: Seizure severity, neurodegeneration, and oxidative stress

Ramos‐Riera,

Beltrán‐Parrazal,

Morgado‐Valle

et al. 2024

Epilepsia Open

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ObjectiveThe goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures.MethodsDM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium–pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro‐Jade B (F‐JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS).ResultsDM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation.SignificanceDM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE‐induced OS under these conditions.Plain Language SummaryOur research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure‐induced neuron cell death. However, even when long‐term seizures promote an imbalance between brain pro‐oxidants and antioxidants, DM2 does not exacerbate that disproportion.

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Sodium‐glucose cotransporter 1/2 inhibition and risk of neurodegenerative disorders: A Mendelian randomization study

Liu,

Shi,

Shao

2024

Brain and Behavior

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IntroductionThis study aims to evaluate the effects of sodium‐glucose cotransporter 1 inhibitors (SGLT1i) and sodium‐glucose cotransporter 2 inhibitors (SGLT2i) on neurodegenerative disorders and to investigate the role of hemoglobin A1c (HbA1c) levels.MethodsUtilizing drug target Mendelian randomization, we employed single nucleotide polymorphisms (SNPs) proximal to the SLC5A1 and SLC5A2 genes to analyze the influence of SGLT1i and SGLT2i on Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), frontotemporal dementia (FTD), Lewy body dementia (LBD), and amyotrophic lateral sclerosis (ALS), with type 2 diabetes (T2D) as a positive control. An additional analysis examined the impact of HbA1c levels on the same disorders.ResultsSGLT1i exhibited a significant association with decreased risk for ALS and MS. Conversely, SGLT2i were linked to an increased risk of AD, PD, and MS. Elevated HbA1c levels, independent of SGLT1 and SGLT2 effects, were associated with an increased risk of PD. Sensitivity analyses supported the robustness of these findings.ConclusionOur study suggests that SGLT1i may confer protection against ALS and MS, whereas SGLT2i could elevate the risk of AD, PD, and MS. Additionally, elevated HbA1c levels emerged as a risk factor for PD. These findings underscore the importance of personalized approaches in the utilization of SGLT inhibitors, considering their varying impacts on the risks of neurodegenerative diseases.

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Role of Modulation of Hippocampal Glucose Following Pilocarpine-Induced Status Epilepticus

Cited by 10 publications

References 120 publications

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

Metabolomics of cerebrospinal fluid reveals prognostic biomarkers in pediatric status epilepticus

Type 2 diabetes mellitus facilitates status epilepticus in adult rats: Seizure severity, neurodegeneration, and oxidative stress

Sodium‐glucose cotransporter 1/2 inhibition and risk of neurodegenerative disorders: A Mendelian randomization study

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